Medical Specialties Commons^™

Accuracy And Practical Considerations For Doubly Labeled Water Analysis In Nutrition Studies Using A Laser-Based Isotope Instrument (Off-Axis Integrated Cavity Output Spectroscopy), Linda M Reynard, William W Wong, Noreen Tuross

Children’s Nutrition Research Center Staff Publications

Background: Given the utility of the doubly labeled water (DLW) method for determination of energy expenditure, additional techniques for isotope analysis of the samples are welcome. Laser-based instruments are one such new analytical tool, but their accuracy and feasibility for DLW studies are grossly understudied.

Objectives: We assessed the accuracy of laser-based isotope ratio measurements as part of the DLW method for estimation of carbon dioxide production rate (rCO2) and total energy expenditure (TEE), in between-group comparison study designs.

Methods: Urine samples from a previous study were analyzed with a laser-based instrument [off-axis integrated cavity output spectroscopy (OA-ICOS)]. In that …

Pressure-Mediated Reflection Spectroscopy Criterion Validity As A Biomarker Of Fruit And Vegetable Intake: A 2-Site Cross-Sectional Study Of 4 Racial Or Ethnic Groups, Stephanie B Jilcott Pitts, Nancy E Moran, Qiang Wu, Lisa Harnack, Neal E Craft, Neil Hanchard, Ronny Bell, Stacey G Moe, Nevin Johnson, Justice Obasohan, Pamela L Carr-Manthe, Melissa N Laska

Children’s Nutrition Research Center Staff Publications

Background: Valid biomarkers of fruit and vegetable (FV) intake are needed for field-based nutrition research.

Objectives: To examine criterion-related validity of pressure-mediated reflection spectroscopy as a proxy measure of FV intake, using plasma carotenoids and self-reported FV and carotenoid intake as primary and secondary criterion measures, respectively.

Methods: Healthy adults 18-65 y of age, self-identifying as African American/black (n = 61), Asian (n = 53), white (n = 70), or Hispanic (n = 29), in North Carolina and Minnesota were recruited. Skin carotenoids were assessed via pressure-mediated reflection spectroscopy (Veggie Meter), skin melanin via spectrophotometer, and total plasma carotenoid concentration …

Epigenetic Silencing Of Tumor Suppressor Lncrna Nkila: Implication On Nf-Κb Signaling In Non-Hodgkin’S Lymphoma, Min-Yue Zhang, George Calin, Ming-Dan Deng, Rex K H Au-Yeung, Lu-Qian Wang, Chor-Sang Chim

Faculty, Staff and Student Publications

The long non-coding RNA (lncRNA) NKILA, localized to 20q13.31, is a negative regulator of NF-κB signaling implicated in carcinogenesis. As a CpG island is embedded in the promoter region of NKILA, it is hypothesized as a tumor suppressor lncRNA silenced by promoter DNA methylation in non-Hodgkin’s lymphoma (NHL). By pyrosequencing-verified methylation-specific PCR, NKILA methylation was detected in 1/10 (10%) NHL cell lines, but not in normal peripheral blood buffy coats or tonsils. NKILA methylation correlated with the repression of NKILA in cell lines. Hypomethylation treatment with 5-Aza-2′-deoxycytidine resulted in promoter demethylation and the re-expression of NKILA. In 102 …

Cxcl10 Chemokine Regulates Heterogeneity Of The Cd8+ T Cell Response And Viral Set Point During Chronic Infection, Aleksandra J Ozga, Melvyn T Chow, Mateus E Lopes, Rachel L Servis, Mauro Di Pilato, Philippe Dehio, Jeffrey Lian, Thorsten R Mempel, Andrew D Luster

Faculty, Staff and Student Publications

CD8+ T cells responding to chronic infection adapt an altered differentiation program that provides some restrain on pathogen replication yet limits immunopathology. This adaptation is imprinted in stem-like cells and propagated to their progeny. Understanding the molecular control of CD8+ T cell differentiation in chronic infection has important therapeutic implications. Here, we found that the chemokine receptor CXCR3 was highly expressed on viral-specific stem-like CD8+ T cells and that one of its ligands, CXCL10, regulated the persistence and heterogeneity of responding CD8+ T cells in spleens of mice chronically infected with lymphocytic choriomeningitis virus. CXCL10 was produced by inflammatory monocytes …

Mapk4 Promotes Triple Negative Breast Cancer Growth And Reduces Tumor Sensitivity To Pi3k Blockade, Wei Wang, Dong Han, Qinbo Cai, Tao Shen, Bingning Dong, Michael T Lewis, Runsheng Wang, Yanling Meng, Wolong Zhou, Ping Yi, Chad J Creighton, David D Moore, Feng Yang

Faculty, Staff and Students Publications

About 15-20% of breast cancer (BCa) is triple-negative BCa (TNBC), a devastating disease with limited therapeutic options. Aberrations in the PI3K/PTEN signaling pathway are common in TNBC. However, the therapeutic impact of PI3K inhibitors in TNBC has been limited and the mechanism(s) underlying this lack of efficacy remain elusive. Here, we demonstrate that a large subset of TNBC expresses significant levels of MAPK4, and this expression is critical for driving AKT activation independent of PI3K and promoting TNBC cell and xenograft growth. The ability of MAPK4 to bypass PI3K for AKT activation potentially provides a direct mechanism regulating tumor sensitivity …

Transcranial Direct Current Stimulation On Parkinson’S Disease: Systematic Review And Meta-Analysis, Paloma Cristina Alves De Oliveira, Thiago Anderson Brito De Araújo, Daniel Gomes Da Silva Machado, Abner Cardoso Rodrigues, Marom Bikson, Suellen Marinho Andrade, Alexandre Hideki Okano, Hougelle Simplicio, Rodrigo Pegado, Edgard Morya

Publications and Research

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson’s disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.

Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.

Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Faculty, Staff and Student Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

Total Energy Expenditure Is Repeatable In Adults But Not Associated With Short-Term Changes In Body Composition, Rebecca Rimbach, Yosuke Yamada, Hiroyuki Sagayama, Philip N Ainslie, Lene F Anderson, Liam J Anderson, Lenore Arab, Issaad Baddou, Kweku Bedu-Addo, Ellen E Blaak, Stephane Blanc, Alberto G Bonomi, Carlijn V C Bouten, Pascal Bovet, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Graeme L Close, Jamie A Cooper, Sai Krupa Das, Lara R Dugas, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Annelies H Goris, Michael Gurven, Catherine Hambly, Asmaa El Hamdouchi, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Kitty P Kempen, Misaka Kimura, William E Kraus, Robert F Kushner, Estelle V Lambert, William R Leonard, Nader Lessan, Corby K Martin, Anine C Medin, Erwin P Meijer, James C Morehen, James P Morton, Marian L Neuhouser, Theresa A Nicklas, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Roberto A Rabinovich, Susan B Racette, David A Raichlen, Eric Ravussin, Rebecca M Reynolds, Susan B Roberts, Albertine J Schuit, Anders M Sjödin, Eric Stice, Samuel S Urlacher, Giulio Valenti, Ludo M Van Etten, Edgar A Van Mil, Jonathan C K Wells, George Wilson, Brian M Wood, Jack Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Cornelia U Loechl, Amy H Luke, Jennifer Rood, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman, Herman Pontzer

Children’s Nutrition Research Center Staff Publications

Low total energy expenditure (TEE, MJ/d) has been a hypothesized risk factor for weight gain, but repeatability of TEE, a critical variable in longitudinal studies of energy balance, is understudied. We examine repeated doubly labeled water (DLW) measurements of TEE in 348 adults and 47 children from the IAEA DLW Database (mean ± SD time interval: 1.9 ± 2.9 y) to assess repeatability of TEE, and to examine if TEE adjusted for age, sex, fat-free mass, and fat mass is associated with changes in weight or body composition. Here, we report that repeatability of TEE is high for adults, but …

Risk Factors For Acute Respiratory Infections In Children Between 0 And 23 Months Of Age In A Peri-Urban District In Pakistan: A Matched Case–Control Study, Fatima Mir, Shabina Ariff, Maria Asif Bhura, Suhail Chanar, Aspara Ali, Muhammad Jawwad, A Hussain, Arjumand Rizvi, Muhammad Umer, Zahid Memon, Atif Habib, Sajid Bashir Soofi, Zulfiqar Ahmed Bhutta

Department of Paediatrics and Child Health

Background: Acute respiratory infection (ARI) accounts for nearly 15% of all childhood mortality in South Asia, with children from rural areas at higher risk due to inaccessibility to healthcare facilities. We therefore aimed to identify risk factors associated with ARI in children under 2 years of age in rural Pakistan.
Methods: A retrospective 1:2 matched case-control study was conducted between October and December 2018 in Taluka Kotri, Jamshoro District of Pakistan. Cases were identified as children between 0 and 23 months of age with a history of fever, cough, sore throat, fast breathing, difficulty breathing, or chest indrawing in the …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Faculty, Staff and Student Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

The Allergy Mediator Histamine Confers Resistance To Immunotherapy In Cancer Patients Via Activation Of The Macrophage Histamine Receptor H1, Hongzhong Li, Yi Xiao, Qin Li, Jun Yao, Xiangliang Yuan, Yuan Zhang, Xuedong Yin, Yohei Saito, Huihui Fan, Ping Li, Wen-Ling Kuo, Angela Halpin, Don L Gibbons, Hideo Yagita, Zhongming Zhao, Da Pang, Guosheng Ren, Cassian Yee, J Jack Lee, Dihua Yu

Duncan NRI Faculty and Staff Publications

Reinvigoration of antitumor immunity remains an unmet challenge. Our retrospective analyses revealed that cancer patients who took antihistamines during immunotherapy treatment had significantly improved survival. We uncovered that histamine and histamine receptor H1 (HRH1) are frequently increased in the tumor microenvironment and induce T cell dysfunction. Mechanistically, HRH1-activated macrophages polarize toward an M2-like immunosuppressive phenotype with increased expression of the immune checkpoint VISTA, rendering T cells dysfunctional. HRH1 knockout or antihistamine treatment reverted macrophage immunosuppression, revitalized T cell cytotoxic function, and restored immunotherapy response. Allergy, via the histamine-HRH1 axis, facilitated tumor growth and induced immunotherapy resistance in mice and humans. …

Mutations In Hcfc1 And Ronin Result In An Inborn Error Of Cobalamin Metabolism And Ribosomopathy, Tiffany Chern, Annita Achilleos, Xuefei Tong, Matthew C Hill, Alexander B Saltzman, Lucas C Reineke, Arindam Chaudhury, Swapan K Dasgupta, Yushi Redhead, David Watkins, Joel R Neilson, Perumal Thiagarajan, Jeremy B A Green, Anna Malovannaya, James F Martin, David S Rosenblatt, Ross A Poché

Faculty, Staff and Students Publications

Combined methylmalonic acidemia and homocystinuria (cblC) is the most common inborn error of intracellular cobalamin metabolism and due to mutations in Methylmalonic Aciduria type C and Homocystinuria (MMACHC). Recently, mutations in the transcriptional regulators HCFC1 and RONIN (THAP11) were shown to result in cellular phenocopies of cblC. Since HCFC1/RONIN jointly regulate MMACHC, patients with mutations in these factors suffer from reduced MMACHC expression and exhibit a cblC-like disease. However, additional de-regulated genes and the resulting pathophysiology is unknown. Therefore, we have generated mouse models of this disease. In addition to exhibiting loss of Mmachc, metabolic perturbations, and developmental defects previously …

Secretogranin Iii Stringently Regulates Pathological But Not Physiological Angiogenesis In Oxygen-Induced Retinopathy, Chang Dai, Prabuddha Waduge, Liyang Ji, Chengchi Huang, Ye He, Hong Tian, Elizabeth Zuniga-Sanchez, Amit Bhatt, Iok-Hou Pang, Guanfang Su, Keith A Webster, Wei Li

Faculty, Staff and Students Publications

Conventional angiogenic factors, such as vascular endothelial growth factor (VEGF), regulate both pathological and physiological angiogenesis indiscriminately, and their inhibitors may elicit adverse side effects. Secretogranin III (Scg3) was recently reported to be a diabetes-restricted VEGF-independent angiogenic factor, but the disease selectivity of Scg3 in retinopathy of prematurity (ROP), a retinal disease in preterm infants with concurrent pathological and physiological angiogenesis, was not defined. Here, using oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, we quantified an exclusive binding of Scg3 to diseased versus healthy developing neovessels that contrasted sharply with the ubiquitous binding of VEGF. Functional immunohistochemistry visualized …

Rethinking Integration Of Environmental And Behavioral Stressors; Back To Energy Homeostasis And Function, Patricia E. Molina

School of Medicine Faculty Publications

No abstract provided.

3’Aqtl-Atlas: An Atlas Of 3’Utr Alternative Polyadenylation Quantitative Trait Loci Across Human Normal Tissues, Ya Cui, Fanglue Peng, Dan Wang, Yumei Li, Jason Sheng Li, Lei Li, Wei Li

Faculty, Staff and Students Publications

Genome-wide association studies (GWAS) have identified thousands of non-coding single-nucleotide polymorphisms (SNPs) associated with human traits and diseases. However, functional interpretation of these SNPs remains a significant challenge. Our recent study established the concept of 3' untranslated region (3'UTR) alternative polyadenylation (APA) quantitative trait loci (3'aQTLs), which can be used to interpret ∼16.1% of GWAS SNPs and are distinct from gene expression QTLs and splicing QTLs. Despite the growing interest in 3'aQTLs, there is no comprehensive database for users to search and visualize them across human normal tissues. In the 3'aQTL-atlas (https://wlcb.oit.uci.edu/3aQTLatlas), we provide a comprehensive list of 3'aQTLs containing …

Analysis Of Zero Balancing Case Studies Through An Occupational Therapy Lens, Deanna Waggy Otr, Msa, Czb, Csla

Journal of Transformative Touch

Does Zero Balancing positively impact occupational performance? This is a question many Occupational Therapists (OTs) ask when discerning if Zero Balancing (ZB) is an evidence-based treatment modality. Case studies from the book Experiencing the Power of Zero Balancing: Case Studies of Journeys to Health and Wholeness (Quarry & King, 2016) were reviewed and compared to the Occupational Therapy domain of practice to show clear evidence that each case study had a positive impact on occupational performance. A comparison chart shows a direct link between the occupational categories and documented evidence of improved occupational performance through practitioner observation and client feedback …

In Situ Structure Of The Acrab-Tolc Efflux Pump At Subnanometer Resolution, Muyuan Chen, Xiaodong Shi, Zhili Yu, Guizhen Fan, Irina I Serysheva, Matthew L Baker, Ben F Luisi, Steven J Ludtke, Zhao Wang

Faculty, Staff and Students Publications

The tripartite AcrAB-TolC assembly, which spans both the inner and outer membranes in Gram-negative bacteria, is an efflux pump that contributes to multidrug resistance. Here, we present the in situ structure of full-length Escherichia coli AcrAB-TolC determined at 7 Å resolution by electron cryo-tomography. The TolC channel penetrates the outer membrane bilayer through to the outer leaflet and exhibits two different configurations that differ by a 60° rotation relative to the AcrB position in the pump assembly. AcrA protomers interact directly with the inner membrane and with AcrB via an interface located in proximity to the AcrB ligand-binding pocket. Our …

Sensory Processing Abnormalities In Community-Dwelling Older Adults With Cognitive Impairment: A Mixed Methods Study, Elizabeth K. Rhodus, Elizabeth G. Hunter, Graham D. Rowles, Shoshana H. Bardach, Kelly Parsons, Justin M. Barber, Maryellen Thompson, Gregory A. Jicha

Sanders-Brown Center on Aging Faculty Publications

Mild cognitive impairment (MCI) or dementia often leads to behavioral and psychiatric symptoms of dementia (BPSD). Sensory processing abnormalities may be associated with BPSD. The purpose of this study was to explore relationships among sensory processing, behavior, and environmental features within the homes of people with MCI or dementia. This project used mixed methods to assess participants’ sensory processing, care partner perspectives on behaviors, and in situ observations of the home environment. Nine participants with cognitive impairment (MCI n = 8, early dementia = 1) and their care partners were included. Seven participants with cognitive impairment were reported to have …

Aav5 Delivery Of Crispr-Cas9 Supports Effective Genome Editing In Mouse Lung Airway, Shun-Qing Liang, Christopher J Walkey, Alexa E Martinez, Qin Su, Mary E Dickinson, Dan Wang, William R Lagor, Jason D Heaney, Guangping Gao, Wen Xue

Faculty, Staff and Students Publications

Genome editing in the lung has the potential to provide long-term expression of therapeutic protein to treat lung genetic diseases. Yet efficient delivery of CRISPR to the lung remains a challenge. The NIH Somatic Cell Genome Editing (SCGE) Consortium is developing safe and effective methods for genome editing in disease tissues. Methods developed by consortium members are independently validated by the SCGE small animal testing center to establish rigor and reproducibility. We have developed and validated a dual adeno-associated virus (AAV) CRISPR platform that supports effective editing of a lox-stop-lox-Tomato reporter in mouse lung airway. After intratracheal injection of the …

Transcranial Stimulation Of Alpha Oscillations Up-Regulates The Default Mode Network, Kevin J Clancy, Jeremy A Andrzejewski, Yuqi You, Jens T Rosenberg, Mingzhou Ding, Wen Li

Faculty, Staff and Student Publications

The default mode network (DMN) is the most-prominent intrinsic connectivity network, serving as a key architecture of the brain's functional organization. Conversely, dysregulated DMN is characteristic of major neuropsychiatric disorders. However, the field still lacks mechanistic insights into the regulation of the DMN and effective interventions for DMN dysregulation. The current study approached this problem by manipulating neural synchrony, particularly alpha (8 to 12 Hz) oscillations, a dominant intrinsic oscillatory activity that has been increasingly associated with the DMN in both function and physiology. Using high-definition alpha-frequency transcranial alternating current stimulation (α-tACS) to stimulate the cortical source of alpha oscillations, …

Sensei: How Many Samples To Tell A Change In Cell Type Abundance?, Shaoheng Liang, Jason Willis, Jinzhuang Dou, Vakul Mohanty, Yuefan Huang, Eduardo Vilar, Ken Chen

Faculty, Staff and Student Publications

Cellular heterogeneity underlies cancer evolution and metastasis. Advances in single-cell technologies such as single-cell RNA sequencing and mass cytometry have enabled interrogation of cell type-specific expression profiles and abundance across heterogeneous cancer samples obtained from clinical trials and preclinical studies. However, challenges remain in determining sample sizes needed for ascertaining changes in cell type abundances in a controlled study. To address this statistical challenge, we have developed a new approach, named Sensei, to determine the number of samples and the number of cells that are required to ascertain such changes between two groups of samples in single-cell studies. Sensei expands …

Autophagosomes Fuse To Phagosomes And Facilitate The Degradation Of Apoptotic Cells In Caenorhabditis Elegans, Omar Peña-Ramos, Lucia Chiao, Xianghua Liu, Xiaomeng Yu, Tianyou Yao, Henry He, Zheng Zhou

Faculty, Staff and Students Publications

Autophagosomes are double-membrane intracellular vesicles that degrade protein aggregates, intracellular organelles, and other cellular components. During the development of the nematode Caenorhabditis elegans, many somatic and germ cells undergo apoptosis. These cells are engulfed and degraded by their neighboring cells. We discovered a novel role of autophagosomes in facilitating the degradation of apoptotic cells using a real-time imaging technique. Specifically, the double-membrane autophagosomes in engulfing cells are recruited to the surfaces of phagosomes containing apoptotic cells and subsequently fuse to phagosomes, allowing the inner vesicle to enter the phagosomal lumen. Mutants defective in the production of autophagosomes display significant …

Nutritional Support And Prophylaxis Of Azithromycin For Pregnant Women To Improve Birth Outcomes In Peri-Urban Slums Of Karachi, Pakistan-A Protocol Of Multi-Arm Assessor-Blinded Randomized Controlled Trial (Mumta Pw Trial), Ameer Muhammad, Zoha Zahid Fazal, Benazir Baloch, Muhammad Imran Nisar, Fyezah Jehan, Yasir Shafiq

Medical College Documents

Background: Maternal undernutrition is critical in the etiology of poor perinatal outcomes and accounts for 20% of small-for-gestational-age (SGA) births. High levels of food insecurity, antenatal undernourishment, and childhood undernutrition necessitate the supplementation of fortified balanced energy protein (BEP) during pregnancy in low-income settings especially with scarce literature available in this subject. Hence, this paper extensively covers the protocol of such a trial conducted in an urban slum of Karachi, Pakistan.
Methods: The trial is community-based, open-labelled, four-arm, and randomized controlled that will include parallel group assignments with a 1:1:1:1 allocation ratio in low-income squatter settlements in urban Karachi, Pakistan. …

Venetoclax Plus Azacitidine In Japanese Patients With Untreated Acute Myeloid Leukemia Ineligible For Intensive Chemotherapy, Kazuhito Yamamoto, Atsushi Shinagawa, Courtney D Dinardo, Keith W Pratz, Kenichi Ishizawa, Toshihiro Miyamoto, Norio Komatsu, Yasuhiro Nakashima, Chikashi Yoshida, Noriko Fukuhara, Kensuke Usuki, Takahiro Yamauchi, Noboru Asada, Norio Asou, Ilseung Choi, Yasushi Miyazaki, Hideyuki Honda, Sumiko Okubo, Misaki Kurokawa, Ying Zhou, Jiuhong Zha, Jalaja Potluri, Itaru Matsumura

Faculty, Staff and Student Publications

Background: The phase 3 VIALE-A trial (NCT02993523) reported that venetoclax-azacitidine significantly prolonged overall survival compared with placebo-azacitidine in patients with newly diagnosed acute myeloid leukemia ineligible for intensive chemotherapy. Herein, efficacy and safety of venetoclax-azacitidine are analyzed in the Japanese subgroup of VIALE-A patients.

Methods: Eligible Japanese patients were randomized 2:1 to venetoclax-azacitidine (N = 24) or placebo-azacitidine (N = 13). Primary endpoints for Japan were overall survival and complete response (CR) + CR with incomplete hematologic recovery (CRi). Venetoclax (target dose 400 mg) was given orally once daily. Azacitidine (75 mg/m2) was administered subcutaneously or intravenously on …

The Efficacy And Safety Of Thrombopoietin Receptor Agonists In Patients With Chronic Liver Disease Undergoing Elective Procedures: A Systematic Review And Meta-Analysis, Ingrid Lindquist, Sven R Olson, Ang Li, Hanny Al-Samkari, Janice H Jou, Owen J T Mccarty, Joseph J Shatzel

Faculty, Staff and Students Publications

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. …

Current And Novel Neuroregenerative Therapies, Arrin Brooks

Theses, Dissertations and Capstones

Underlying the physical and cognitive deficits consequent of many neuropathologies is one common factor, the loss of neurons. While neurodegenerative diseases, stroke, and traumatic brain injury arise from a variety of etiologies, they all ultimately result in injury and/or death of neuronal cells and concomitant functional deficits. In the present work we primarily focus on current and potential treatments for localized lesions, particularly those in the striatum of Parkinson’s disease (PD) or the cortex as in stroke. First, we discuss a new surgical technique for deep brain stimulator (DBS) placement, as DBS is a mainstay treatment for movement disorders including …

Physical Therapy Interventions And Outcomes In A Patient With Transfemoral Amputation Following Sound Side Total Knee Arthroplasty: A Case Report, Scott Love, Debra Gray, Jenna Yent, Michael Jason Highsmith

Physical Therapy Collection

Background: Following a transfemoral amputation (TFA), osteoarthritis (OA) on the sound limb may occur secondary to overuse. Potential causative factors include gait abnormalities, increased knee load, and performing hopping activities without a prosthesis. Unilateral TFA patients may require a total knee arthroplasty (TKA) to improve function.

Case Description and Methods: A 56-year-old male with a TFA who was diagnosed with left knee OA and was classified as a limited community ambulator underwent a TKA to restore function. The purpose of this case report is to determine the benefits of standard physical therapy (PT) augmented by a high intensity, whole-body …

Expanding The Landscape Of Amino Acid-Rich Antimicrobial Peptides: Definition, Deployment In Nature, Implications For Peptide Design And Therapeutic Potential, Aaron P. Decker, Abraham F. Mechesso, Guangshun Wang

Journal Articles: Pathology and Microbiology

Unlike the α-helical and β-sheet antimicrobial peptides (AMPs), our knowledge on amino acid-rich AMPs is limited. This article conducts a systematic study of rich AMPs (>25%) from different life kingdoms based on the Antimicrobial Peptide Database (APD) using the program R. Of 3425 peptides, 724 rich AMPs were identified. Rich AMPs are more common in animals and bacteria than in plants. In different animal classes, a unique set of rich AMPs is deployed. While histidine, proline, and arginine-rich AMPs are abundant in mammals, alanine, glycine, and leucine-rich AMPs are common in amphibians. Ten amino acids (Ala, Cys, Gly, His, …

Childhood Trauma And Chronic Disease, Breanna Urena

Graduate Research Projects

No abstract provided.

Repeated Exposure To Chlorpyrifos Is Associated With A Dose-Dependent Chronic Neurobehavioral Deficit In Adult Rats, Ana C. R. Ribeiro, Elisa Hawkins, Fay M. Jahr, Joseph L. Mcclay, Laxmikant Deshpande

Neurology Publications

Organophosphate (OP) chemicals include commonly used pesticides and chemical warfare agents, and mechanistically they are potent inhibitors of the cholinesterase (ChE) enzyme. Epidemiological studies report long-term neuropsychiatric issues, including depression and cognitive impairments in OP-exposed individuals. Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. Multiple laboratory studies have reported on either the long-term behavioral effect of an acute high-dose CPF (30-250 mg/kg) or studied sub-chronic behavioral effects, particularly the motor and cognitive effects of repeated low-dose CPF. However, studies are lacking on chronic mood and depression-related morbidities following repeated CPF doses that would mimic occupationally relevant OP …