Medical Specialties Commons^™

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

The Diabetes Prevention Program And Its Outcomes Study: Niddk's Journey Into The Prevention Of Type 2 Diabetes And Its Public Health Impact, Jill P Crandall, Dana Dabelea, William C Knowler, David M Nathan, Marinella Temprosa, Dpp Research Group

Children’s Nutrition Research Center Staff Publications

The current-day epidemic of type 2 diabetes, largely driven by increased adiposity and reduced physical activity in the setting of genetic susceptibility, is a major public health challenge. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) presciently proposed the Diabetes Prevention Program (DPP), a multicenter randomized clinical trial, designed by investigators in conjunction with NIDDK staff and initiated in 1996. The primary goal of DPP was to determine whether an intensive lifestyle intervention (ILS) or metformin in comparison with placebo would reduce the development of diabetes in a high-risk population with prediabetes. After mean 2.8 years, ILS …

Metabolic Clearance Rate Of Insulin Across The Glucose Tolerance Spectrum By Race And Ethnicity In Youth With Obesity, Wonhee Cho, Fida Bacha, Hala Tfayli, Sojung Lee, Sara F Michaliszyn, Joon Young Kim, Silva Arslanian

Children’s Nutrition Research Center Staff Publications

Objective: Despite β-cell failure in youth with dysglycemia (i.e., impaired glucose tolerance [IGT] and type 2 diabetes), fasting insulin (FI) concentrations are elevated. Herein, we examined the following: 1) metabolic clearance rate of insulin (MCRI) in youth with obesity and normal glucose tolerance (NGT) versus those with IGT versus those with type 2 diabetes; 2) racial and ethnic differences in insulin dynamics; and 3) metabolic/adiposity correlates of MCRI.

Methods: A total of 206 youth underwent assessment of fasting glucose, FI, MCRI and peripheral insulin sensitivity (PIS), first-phase insulin secretion, disposition index, body composition, and abdominal adiposity.

Results: In type 2 …

To Pause With A Cliffhanger Or A Temporary Closure? The Differential Impact Of Serial Versus Episodic Narratives On Children's Physical Activity Behaviors, Amy Shirong Lu, Melanie C Green, Caio Victor Sousa, Jungyun Hwang, I-Min Lee, Debbe Thompson, Tom Baranowski

Children’s Nutrition Research Center Staff Publications

Research has supported the effectiveness of narratives for promoting health behavior, but different narrative presentation formats (serial vs. episodic) have seldom been compared. Suspense theories suggest that serial narratives, which do not provide a full resolution at the end of an episode, may create higher motivation for continued engagement with a story. Forty-four 8 to 12-year-old children were randomly assigned to watch an animation series designed for an existing active video game in which the plot was delivered either continuously across multiple episodes (serial) or in multiple yet relatively independent self-contained episodes (episodic). Controlling for social desirability, children who watched …

Inhibition Of Srebp-1c Rescues Hepatic Cyp7b1 Expression And Bile Acid Synthesis In Malnourished Mice, Xiaoyang Wan, Krishnakant G Soni, Jong Min Choi, Sun Yun Jung, Margaret E Conner, Geoffrey A Preidis

Faculty, Staff and Students Publications

Malnutrition decreases intestinal bile acids, resulting in inefficient nutrient absorption and impaired catch-up growth. Mechanisms by which bile acid depletion occurs in malnutrition are unknown. Using a mouse model of early-life malnutrition, we explored bile acid homeostasis, focusing on transcriptional repression of CYP7B1, a rate-limiting enzyme in the alternative pathway of bile acid biosynthesis, by SREBP-1c, a master regulator of lipid metabolism. Mice were maintained on a low-protein low-fat or isocaloric control chow until eight weeks of age when livers were harvested for proteome profiling, western blot, RT-qPCR, and chromatin immunoprecipitation. Cultured hepatocytes and mice were treated with the SREBP-1c …

Metabolomic Data May Support The Development Of Personalized Nutrition Approaches To Type 2 Diabetes Management, Danielle J Lee, Shragvi Balaji, Jerome I Rotter, Alexis C Wood

Faculty, Staff and Students Publications

Diet is a major modifiable risk factor for type 2 diabetes (T2D), and suboptimal diets continue to contribute substantially to the population burden of T2D. Personalized nutrition proponents argue that specializing recommendations to interindividual differences in diet-health relationships will yield reductions in disease risk. However, how to personalize diet, and to whom, to reduce T2D risk remains unclear. Metabolites offer promise in this respect, as they capture (in part) dietary intake after the processes of digestion, processing, and absorption. The incorporation of metabolite data into diet-health studies therefore offers the opportunity to examine how the effects of food on the …

Bibliometric Analysis Of Congenital Toxoplasmosis: A Ten-Year (2013-2023) Review Of Research Publications, Festus Mulakoli, Horatius Musembi, Ann Kimani

School of Nursing & Midwifery, East Africa

Background:Toxoplasma gondii, an obligate intracellular protozoan, infects more than one-third of the global population and causes toxoplasmosis, which can lead to severe fetal complications in pregnant women. The global prevalence of latent toxoplasmosis in pregnant women is 33.8%, with regional variations and risk factors, including the consumption of undercooked meat, exposure to cat feces, and consumption of contaminated water. Pregnant women lack sufficient awareness of these risk factors, necessitating enhanced education, regular screening, and counseling during antenatal care for early detection and management.

Aim: This study performed a comprehensive bibliometric analysis of research on congenital toxoplasmosis published between 2013 …

First-In-Human Phase 1 Study Of Khk2455 Monotherapy And In Combination With Mogamulizumab In Patients With Advanced Solid Tumors, Timothy A Yap, Olivier Rixe, Capucine Baldini, Ursa Brown-Glaberman, Sergey Efuni, David S Hong, Christophe Massard, Jameel Muzaffar, Andreea Varga, Emrullah Yilmaz, Yuta Ikawa, Lisa H Shiue, Yi Liu, Matthew W Hruska, Henry Zhao, Akihiro Tokunaga, Solmaz Sahebjam

Faculty, Staff and Student Publications

Background: Indoleamine 2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that degrades tryptophan (Trp) to kynurenine (Kyn), which suppresses effector T cells and reduces antitumor activity. KHK2455 is a long-acting selective IDO1 inhibitor that blocks the heme component of the IDO holoenzyme. Mogamulizumab is a humanized immunoglobulin G1 monoclonal antibody targeting CCR4. KHK2455 + mogamulizumab demonstrated enhanced antitumor activity in preclinical studies, which led to a first-in-human, two-part, multicenter, open-label, phase 1, dose-escalation, cohort-expansion trial (ClinicalTrials.gov identifier NCT02867007) evaluating the safety/tolerability, pharmacokinetics, and IDO1 activity of KHK2455 alone and in combination with mogamulizumab in patients with treatment-refractory advanced solid tumors. …

Proceedings Of The 2025 Nassi Annual Meeting, Patrick C. Hsieh, Chiung-Chyi Shen, Alan S. Hilibrand, D. Scott Kreine, David R. O’Brien Jr., Hani H. Mhaidli, Jau-Ching Wu, Wen-Cheng Huang

Department of Orthopaedic Surgery Faculty Papers

No abstract provided.

The Loss Of Opa1 Accelerates Intervertebral Disc Degeneration And Osteoarthritis In Aged Mice, Vedavathi Madhu, Miriam Hernandaz-Meadows, Ashley Coleman, Kimheak Sao, Kameron Inguito, Owen Haslam, Paige Boneski, Hiromi Sesaki, Ruteja Barve, John Collins, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

Recent studies have highlighted the importance of mitochondria in NP cells and articular chondrocyte health. Since the understanding of mechanisms governing mitochondrial dynamics in these tissues is lacking, we investigated the role of OPA1, a mitochondrial fusion protein, in their homeostasis. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and loss resulted in the dysregulation of autophagy. Metabolic profiling and

Validation Of Established Thyroid Ultrasound Volume Norms In A Chernobyl Cohort, Lydia B. Zablotska, Robert J. Mcconnell, Aleksandr V. Rozhko, Patrick O'Kane, Vasilina Yauseyenka, Mark P. Little, Victor Minenko, Vladimir Drozdovitch, Tamara Moskvicheva, Maureen Hatch, Tamara Yeudachkova, Kiyohiko Mabuchi, Elizabeth K. Cahoon

Department of Radiology Faculty Papers

OBJECTIVE: To establish thyroid ultrasound volume norms appropriate for studies of diffuse goiter in a cohort of children and adolescents from an iodine-deficient population exposed to 131I by the Chernobyl fallout.

METHODS: A cohort of 11,970 Belarusians aged ≤18 years at the time of the 1986 Chernobyl accident with individual thyroid radiation dose estimates was screened 10-18 years later. From these, a low-dose subset of 2,392 with no thyroid diseases was selected to construct age- and sex-specific normative values for thyroid ultrasound volume, compared to Belarusian Ministry of Health (MOH) norms and existing WHO and European standards.

RESULTS: Cohort-specific values …

Clinico-Epidemiological Characteristics Of Cerebral Venous Sinus Thrombosis In Kenya: A Retrospective Case Series, Taby Siika, Jaskirat Sokhi, Juzar Hooker, Sheila Waa, Anne Mwirigi, Jasmit Shah, Dilraj Sokhi

Internal Medicine, East Africa

Background: Cerebral venous sinus thrombosis (CVST) is a rare cause of stroke that is more common in young, especially female, adults and can be challenging to diagnose due to its frequently non-specific presentation and diverse risk factors. Most cases are idiopathic, and international guidelines do not recommend routine investigations for underlying thrombophilia. Timely diagnosis, with prompt neuroimaging and guideline-based treatment, leads to good outcomes. However, in the literature on CVST from sub-Saharan Africa, the gap is substantial, with the few cases described as being related to systemic and/or brain infections. We describe here the largest cohort of CVST from the …

Higher Plasma Afb1 Concentration Is Associated With Increased Risk Of Hpv 16 And Hpv 18 Detection And Persistence Among Ugandan Women, Yan Tong, Miriam Nakalembe, Collins Mpamani, Carolyn Nakisige, Jane Namugga, Grace Banturaki, Philiph Tonui, Elkanah Orang'o

Obstetrics and Gynaecology, East Africa

Introduction: Aflatoxins are environmental hazards; potent carcinogenic and immunosuppressive agents that contaminates corn and other crops. A high proportion of hepatocellular carcinoma cases are caused by exposure to dietary aflatoxins. Cervical cancer is common among Ugandan women; this malignancy is caused by persistent infection with oncogenic HPV types. An analysis was performed to examine associations between plasma aflatoxin B1 (AFB1) detection and oncogenic HPV detection (HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68) and persistence among Ugandan women.

Methods: Ugandan women were enrolled in a prospective cohort study. Annual cervical swabs …

Enzyme-Independent Functions Of Hdac3 In The Adult Hear, Sichong Qian, Chen Zhang, Wenbo Li, Shiyang Song, Guanqiao Lin, Zixiu Cheng, Wenjun Zhou, Huiqi Yin, Yueli Wang, Haiyang Li, Ying H Shen, Zheng Sun

Center on Aging Staff Publications

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes …

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 …

Covid-19 Vaccine Attitudes And Behaviors Among Pregnant Women In Nairobi, Kenya With Diverse Socio-Economic And Educational Backgrounds, Jessica Schue, Ferdinand Okwaro, Ingrid Gichere, Daizy Cherono, Mandeep Sura, Emilly Miller, Berhaun Fesshaye, Prachi Singh, Marleen Temmerman

Centre of Excellence in Women and Child Health

Introduction: Pregnant women are at increased risk of severe manifestations of COVID-19, resulting in ICU admission, mechanical ventilation, and death compared to non-pregnant women. COVID-19 vaccines were approved for use in pregnant women in early 2022 by the World Health Organization, but permissive policies toward vaccine women differed by country. As education has been associated with vaccine uptake, this study sought to examine the association between socio-economic or educational status and vaccination behaviors, including reasons for vaccination or non-vaccination among pregnant women seeking health care services in Nairobi, Kenya.

Methods: This study administered a survey to pregnant women at the …

Tissue Engineering: History, Principles, Applications, Challenges, And Future Work, Alexa Cesari, Ms

Student Papers, Posters & Projects

Tissue engineering is a comprehensive and cutting-edge field that leverages principles from multiple scientific disciplines to assist in regenerative medicine. It is defined by the most basic structure of the human body, the cell. When an injury occurs, cells send signals to initiate wound healing processes. In most cases, the body is equipped to heal wounds on its own; however, there are instances where wounds are too severe and cannot undergo proper regeneration. When this occurs, alternative measures are taken to assist in wound repair. With numerous advancements made over the years, tissue engineering has become an increasingly common method …

Vitamin D Status And Risk For Breast Cancer In Kenya, Ronald Wasike, Victor Mobegi, Esther Maina, Francis Makokha, Robert Armstrong, Annastacia Mbithi

General Surgery, East Africa

Background: Vitamin D plays a critical role in bone metabolism, calcium regulation, and various cellular processes, including those linked to cancer. The biologically active form, 1,25-dihydroxyvitamin D [1,25(OH)2D], works through the Vitamin D Receptor (VDR). Polymorphisms in VDR and related genes have been associated with cancer risk, including breast cancer. This case-control study aimed to investigate the relationship between serum vitamin D levels and breast cancer among Kenyan women.

Methods: Serum 25-hydroxyvitamin D [25(OH)D] levels were measured in 112 breast cancer patients and 106 controls using electrochemiluminescence.

Results: Results indicated that 81.2% of participants had deficient or insufficient vitamin D …

Labrad : Vol 50, Issue 1 - July 2025, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• EDITORIAL
• ARTICLES
• Molecular Integration in Diagnostic Medicine: The Convergence of Laboratory and Imaging Disciplines Toward Precision Healthcare
• Diagnosis of Odontogenic Cysts: Integrated Approach; Radiology-Pathology Correlation
• Radiologic Correlation in Bone Pathology Diagnosis - Essential Aspect
• Integrated Diagnostics in Microbiology: A Comprehensive Approach to Tuberculosis Diagnosis
• Integrated Diagnostics in Multiple Myeloma
• Sweat and DNA: A Unified Approach to Diagnosing Cystic Fibrosis
• Integrated Breast Biopsy and Predictive Marker Testing: A New Era in Streamlined Cancer Diagnostics
• Unmasking the Hook Effect in Prolactinomas: A Diagnostic Trap Requiring an Integrated Approach
• Radiology-Pathology Correlation: A Cornerstone of Integrated Diagnostic Accuracy
• Integrated Diagnostic Assessment of von Willebrand …

Psychosocial Supports For The Physical And Mental Health Of Youth With Autism And Other Neurodevelopmental Disabilities., Melissa Campbell, Elizabeth Hastings, Paige Mcardle, Darren Olsen, Kathryn Benton, Cy Nadler

Manuscripts, Articles, Book Chapters and Other Papers

One in six youth has a neurodevelopmental disability (NDD), and autism diagnostic rates continue to rise. Before and after a diagnosis, families need trusted sources of guidance to navigate co-occurring medical and psychological conditions, and to manage unique stressors including transition to adulthood. However, medical professionals from all specialty areas struggle to identify resources to support the complex psychosocial and healthcare needs of these patients and their families. This primer on psychosocial supports for youth with autism will explore the major mental and physical health stressors faced by affected youth and families, and discuss opportunities for primary care and other …

Constantly Connected: What Healthcare Providers Need To Know About Vicarious Trauma In An Evolving Digitally Connected Global Community., Meghan Kanya, Patricia Davis, Gail Robertson

Manuscripts, Articles, Book Chapters and Other Papers

Easy access to streaming news and sensational headlines has transformed society's exposure to traumatic narratives. From personal stories on social media platforms to news articles about violence in communities, patients and their caregivers may not recognize their exposure as traumatic nor recognize their psychological sequalae as unhealthy. In addition, youth with trauma-related mental health symptoms are not consistently identified in pediatric primary care clinics. Due to the increase in proximity to traumatic stories, healthcare providers working with youth require additional skills designed to engage patients and families in conversations about exposure to violence via technology and symptoms of vicarious trauma. …

Splenic Function Post Radiation Therapy In Childhood Cancer Survivors, Joy M. Fulbright, Kyla Alsman, Ashley K. Sherman, Kris Laurence, Becky Lowry

Manuscripts, Articles, Book Chapters and Other Papers

Study evaluated splenic function in childhood cancer survivors (CCS) who had received radiation to the spleen utilizing pRBC PIT (vesiculated erythrocytes) count compared to a non-radiated control group. Those exposed to < 20 Gy of radiation had PIT counts not significantly different from the control group. There was trend for higher pRBC PIT count in those exposed to higher doses of radiation.

What Is The Expected Clearance Of Methotrexate? A Therapeutic Drug Monitoring Reference Guide For High-Dose Methotrexate Use In Pediatric Malignancies., Zachary L. Taylor, Tamara P. Miller, Sarah G. Board, Ethan Poweleit, Ashley Chavana, Allison Weisnicht, Austin L. Brown, Melanie B. Bernhardt, Eric S. Schafer, Maureen M. O'Brien, Sharon M. Castellino, Laura Ramsey

Manuscripts, Articles, Book Chapters and Other Papers

High-dose methotrexate dosage and infusion durations differ across treatment protocols for pediatric leukemia, lymphoma, and osteosarcoma. Supportive care interventions are dependent on a patient's elimination of methotrexate (MTX). Therefore, it is important to establish the expected MTX elimination across protocols. Using modeling and simulation of real-world data, we determined the expected MTX concentrations at common time points from the start of infusion (24, 36, 42, 48, 60, and 72 hours) and the time that each patient would reach a typical discharge threshold (0.4, 0.2, 0.15, and 0.10 µM). These data provide a reference for MTX concentrations for common pediatric protocols.

Daily Physical Activity And Cardiorespiratory Fitness In Adults With Down Syndrome With And Without Congenital Heart Disease., Julianne G. Clina, David A. White, Joseph R. Sherman, Jessica C. Danon, Daniel Forsha, Brian C. Helsel, Richard A. Washburn, Joseph E. Donnelly, Lauren T. Ptomey

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Individuals with Down syndrome (DS) typically exhibit lower cardiorespiratory fitness and reduced moderate-to-vigorous physical activity (MVPA) compared to persons without disability. Approximately 50-55 % of individuals with DS have congenital heart disease (CHD), which is associated with cardiopulmonary deficiencies and reduced MVPA participation in non-DS populations. It is unknown if CHD related comorbidities compound with DS associated deficits in physical activity and fitness.

OBJECTIVE: To compare physical activity, cardiorespiratory fitness, and cardiovascular function, of persons with DS with and without CHD.

METHODS: Baseline data were used from a 12-month randomized controlled physical activity intervention of adults with DS. Participants …

Breast And Prostate Cancer Survivors’ Understanding Of Risk And Management Of Cardiovascular And Musculoskeletal Side Effects Of Treatment: Findings From Focus Groups, Jack Dalla Via, Chris R. Andrew, Brenton J. Baguley, Nina Stewart, Jonathan M. Hodgson, Joshua R. Lewis, Mandy Stanley, Mary A. Kennedy

Research outputs 2022 to 2026

Purpose: Survival after a cancer diagnosis is improving, increasing the importance of understanding and managing long-term treatment-related adverse effects. This study aimed to understand breast and prostate cancer survivors’ understanding of how cancer treatment may affect cardiovascular and musculoskeletal health. Methods: Australian breast and prostate cancer survivors treated with therapies with known cardiovascular adverse effects were recruited via a private cancer care provider. Participants completed an online background questionnaire, then participated in a focus group. Focus groups were recorded, transcribed, then analysed using reflexive thematic analysis. Results: In total, 26 cancer survivors (15 breast, 11 prostate; mean age 67 years) …

Minimally Invasive Total Versus Partial Thymectomy For Early-Stage Thymoma, Irene Helenowski, Alex Pohlman, Zaid Abdelsattar

Biostatistics Collaborative Core: Faculty Publications and Other Works

Background/Objectives: Total thymectomy is currently the gold standard operation for treating thymoma. However, recent studies have suggested the potential health consequences of thymus removal in adults, including possible increased autoimmune disease and all-cause mortality. In this context, we assess oncologic outcomes following total vs. partial thymectomy for early-stage thymoma. Methods: We identified patients diagnosed with WHO types A–B3 thymoma between 2010–2021 from a national hospital-based dataset. We excluded patients with stage II or higher disease, open resections and perioperative chemo-/radiation therapy. We stratified patients into total and partial thymectomy cohorts. We used propensity score matching to minimize confounding, …

Distinguishing Pex2 And Pex16 Gene Variant Severity For Mild, Severe And Atypical Peroxisome Biogenesis Disorders, Vanessa A Gomez, Oguz Kanca, Sharayu V Jangam, Saurabh Srivastav, Jonathan C Andrews, Michael F Wangler

Duncan NRI Faculty and Staff Publications

Peroxisomal biogenesis disorders (PBD) are autosomal recessive diseases caused by mutations in specific PEX genes that impair peroxisome formation, leading to multi-systemic failure. Symptoms vary, even in patients with variants in the same PEX gene. Our goal is to select PEX mutations and use Drosophila to model a severity spectrum based on genotype-phenotype correlations. Utilizing KozakGAL4 (KZ) cassettes, we replaced the coding sequence of Pex with a GAL4 driver, ideal for making 'humanized' flies in which human PEX can replace the fly loss. We generated Pex2KZ and Pex16KZ lines and assessed them in various behavior assays, confirming their severe phenotypes. …

Comparison Between Acute Leukemia Screening Tube And Lineage-Specific Panels For The Diagnosis Of Acute Leukemia In Kenya, Nancy Okinda, Geoffrey Omuse, Elizabeth Kagotho, Douglas Munga

Pathology, East Africa

Purpose: Acute leukemia is a group of hematologic malignancies categorized according to the immature cells that proliferate and replace the normal bone marrow. Flow cytometry has emerged as a cornerstone in the diagnosis of hematologic malignancies. Staged analysis with a screening tube containing specific lineage markers determines the need for subsequent testing if there is an abnormal population (blasts). The specific lineage panels to be analyzed are determined depending on the positive markers in the screening tube. This study aimed to determine the agreement of diagnosis using the acute leukemia screening tube (ALST) and the lineage-specific panel.

Methods: This was …

Autologous T Cell Therapy For Prame, Martin Wermke, Dejka M Araujo, Manik Chatterjee, Apostolia M Tsimberidou, Tobias A W Holderried, Amir A Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J Luke, Cedrik M Britten

Faculty, Staff and Student Publications

In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02+ patients with PRAME+ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose …

Memantine Inhibits Calcium-Permeable Ampa Receptors, Elisa Carrillo, Alejandra Montaño Romero, Cuauhtemoc U Gonzalez, Andreea L Turcu, Santiago Vázquez, Edward C Twomey, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Memantine is an US Food and Drug Administration (FDA) approved drug that is thought to selectively inhibit NMDA-subtype of ionotropic glutamate receptors (NMDARs). NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine …