Medicine and Health Sciences Commons^™

Hiding In Plain Sight: Eating Disorders In Diverse Populations - A Case For Comprehensive Medical Education, Tashalee R Brown, Madeline O Jansen, Drew Hirsch, Habiba Amir, Alexis E Duncan, Ginger E Nicol

2020-Current year OA Pubs

BACKGROUND: Training gaps regarding the diagnosis and management of eating disorders in diverse populations, including racial, ethnic, sexual, and gender minoritized groups, have not been thoroughly examined.

OBJECTIVE: This study aimed to examine resident physicians' knowledge and attitudes regarding eating disorders in diverse populations, with a focus on areas for improved training and intervention.

METHODS: Ninety-two resident physicians in internal medicine, emergency medicine, obstetrics/gynecology, psychiatry, and surgery at an academic center completed an online survey from 12/1/2020-3/1/2021, which comprised multiple choice and vignette-style open-ended questions to assess knowledge and attitudes toward the management and clinical presentations of eating disorders. Overall, …

Approaches And Outcomes Of Adalimumab Discontinuation In Patients With Well-Controlled Inflammatory Arthritis: A Systematic Search And Review, Erin Balay-Dustrude, Jessica Fennell, Kevin Baszis, Y Ingrid Goh, Daniel B Horton, Tzielan Lee, Chloe Rotman, Anna Sutton, Marinka Twilt, Olha Halyabar, Carra Jia Inactive Disease Workgroup

2020-Current year OA Pubs

OBJECTIVE: This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides.

METHODS: We conducted a publication search on adalimumab discontinuation from 2000-2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease. Studies included evaluated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA).

RESULTS: Forty-nine studies were included. Studies evaluating adalimumab alone were limited, and many reported TNFi outcomes …

Effectiveness Of An Online Food Shopping Intervention To Reduce Salt Purchases Among Individuals With Hypertension - Findings Of The Saltswitch Online Grocery Shopping (Ogs) Randomised Trial, Jason Hy Wu, Damian Maganja, Liping Huang, Kathy Trieu, Fraser Taylor, Eden M Barrett, Clare Arnott, Xiaoqi Feng, Aletta E Schutte, Gian Luca Di Tanna, Cliona Ni Mhurchu, Adrian J Cameron, Mark D Huffman, Bruce Neal

2020-Current year OA Pubs

BACKGROUND: Online grocery shopping is a growing source of food purchases in many countries. We investigated the effect of nudging consumers towards purchases of lower sodium products using a web browser extension.

METHODS: This trial was conducted among individuals with hypertension who shopped for their groceries online in Australia. From July 2021 to June 2023, participants were randomised to use the SaltSwitch Online Grocery Shopping web browser extension or continue their usual grocery shopping for 12 weeks. The SaltSwitch extension modified a retailer's online shopping interface to suggest similar but lower sodium alternative products to those initially selected. The primary …

Refinement Of An Algorithm To Detect And Predict Freezing Of Gait In Parkinson Disease Using Wearable Sensors, Allison M Haussler, Lauren E Tueth, David S May, Gammon M Earhart, Pietro Mazzoni

2020-Current year OA Pubs

Freezing of gait (FOG) is a debilitating symptom of Parkinson disease (PD). It is episodic and variable in nature, making assessment difficult. Wearable sensors used in conjunction with specialized algorithms, such as our group's pFOG algorithm, provide objective data to better understand this phenomenon. While these methods are effective at detecting FOG retrospectively, more work is needed. The purpose of this paper is to explore how the existing pFOG algorithm can be refined to improve the detection and prediction of FOG. To accomplish this goal, previously collected data were utilized to assess the prediction ability of the current algorithm, the …

Carboxyl Ester Lipase Hybrid 1 (Cel-Hyb1) Haplotypes Confer Varying Risk For Chronic Pancreatitis, Gergő Berke, Xunjun K Xiao, Mark E Lowe, Et Al.

2020-Current year OA Pubs

The CEL-HYB1 hybrid allele of the carboxyl ester lipase (CEL) gene and its pseudogene (CELP) has been associated with chronic pancreatitis (CP). Recent work indicated that amino acid positions 488 and 548 in CEL-HYB1 determined pathogenicity. Haplotype Thr488-Ile548 was associated with CP while haplotypes Thr488-Thr548 and Ile488-Thr548 were benign. However, functional analysis revealed that Thr488 is the primary determinant of CEL-HYB1 misfolding and associated endoplasmic reticulum (ER) stress. To address this contradiction, we analyzed a cohort from Hungary and found significantly increased CEL-HYB1 carrier frequency in CP cases (9/319, 2.8%) versus controls (5/618, 0.8%), yielding an odds ratio of 3.6 …

Cochlear Mechanics Are Preserved After Inner Ear Delivery Of Gold Nanoparticles, Dorothy W Pan, Jinkyung Kim, Patricia M Quiñones, Anthony J Ricci, Brian E Applegate, John S Oghalai

2020-Current year OA Pubs

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea. We sought to assess PSCC infusion of gold NPs into the cochlea, including the NPs' distribution and effect on cochlear mechanics. …

Stereotactic Cardiac Radiotherapy For Refractory Ventricular Tachycardia In Structural Heart Disease Patients: A Systematic Review, Amulya Gupta, Zeeshan Sattar, Nourhan Chaaban, Sagar Ranka, Cameron Carlson, Farhad Sami, Clifford G Robinson, Phillip S Cuculich, Seth H Sheldon, Madhu Reddy, David Akhavan, Amit Noheria

2020-Current year OA Pubs

AIMS: Among patients with structural heart disease with ventricular tachycardia (VT) refractory to medical therapy and catheter ablation, cardiac stereotactic body radiotherapy (SBRT) is a paradigm-changing treatment option. This study aims to assess the efficacy of cardiac SBRT in refractory VT by comparing the rates of VT episodes, anti-tachycardia pacing (ATP) therapies, and implantable cardioverter-defibrillator (ICD) shocks post-SBRT with pre-SBRT.

METHODS AND RESULTS: We performed a comprehensive literature search and included all clinical studies reporting outcomes on cardiac SBRT for VT. Treatment efficacy was evaluated as random-effects pooled rate-ratios of VT episodes, ATP therapies and ICD shocks post-SBRT (after 6-week …

Emata: A Toolbox For The Automatic Extraction And Modeling Of Arterial Inputs For Tracer Kinetic Analysis In [18f]Fdg Brain Studies, Mattia De Francisci, Erica Silvestri, Andrea Bettinelli, Tommaso Volpi, Manu S Goyal, Andrei G Vlassenko, Diego Cecchin, Alessandra Bertoldo

2020-Current year OA Pubs

PURPOSE: PET imaging is a pivotal tool for biomarker research aimed at personalized medicine. Leveraging the quantitative nature of PET requires knowledge of plasma radiotracer concentration. Typically, the arterial input function (AIF) is obtained through arterial cannulation, an invasive and technically demanding procedure. A less invasive alternative, especially for [

METHODS: To assess the toolbox generalizability and present example outputs, EMATA was applied to brain [

RESULTS: EMATA consistently performs IDIF extraction across all datasets, despite differences in scanners and acquisition protocols. Remarkably high agreement is observed when comparing Patlak's K

CONCLUSION: EMATA proved adaptability to different datasets characteristics and …

Lower-Intensity Cpx-351 Plus Venetoclax Induction For Adults With Newly Diagnosed Aml Unfit For Intensive Chemotherapy, Geoffrey L Uy, Vinod Pullarkat, Praneeth Baratam, Robert K Stuart, Roland B Walter, Eric S Winer, Qi Wang, Stefan Faderl, Divya Chakravarthy, Diane Menno, Ronald S Cheung, Tara L Lin

2020-Current year OA Pubs

Preclinical data suggest a rationale for combining CPX-351, a dual-drug liposomal encapsulation of daunorubicin and cytarabine, with venetoclax, a B-cell lymphoma-2 inhibitor. This phase 1b study evaluated lower-intensity CPX-351 combined with venetoclax in adults with acute myeloid leukemia (AML) considered unfit/ineligible for intensive chemotherapy. In a dose-exploration phase using a 3+3 design, patients received stepwise dosing of CPX-351 IV on days 1 and 3 plus venetoclax 400 mg orally on days 2 to 21 per cycle to determine the recommended phase 2 dose (RP2D) for this combination. During the expansion phase, additional patients received CPX-351 plus venetoclax at the identified …

Loss Of Chop Prevents Joint Degeneration And Pain In A Mouse Model Of Pseudoachondroplasia, Jacqueline T Hecht, Alka C Veerisetty, Mohammad G Hossain, Debabrata Patra, Michele Carrer, Frankie Chiu, Dorde Relic, Paymaan Jafar-Nejad, Karen L Posey

2020-Current year OA Pubs

Pseudoachondroplasia (PSACH), a severe dwarfing condition characterized by impaired skeletal growth and early joint degeneration, results from mutations in cartilage oligomeric matrix protein (COMP). These mutations disrupt normal protein folding, leading to the accumulation of misfolded COMP in chondrocytes. The MT-COMP mouse is a murine model of PSACH that expresses D469del human COMP in response to doxycycline and replicates the PSACH chondrocyte and clinical pathology. The basis for the mutant-COMP pathology involves endoplasmic reticulum (ER) stress signaling through the PERK/eIF2α/CHOP pathway. C/EBP homologous protein (CHOP), in conjunction with a TNFα inflammatory process, upregulates mTORC1, hindering autophagy clearance of mutant COMP …

A Phase 1 Randomized Trial Of Homologous And Heterologous Filovirus Vaccines With A Late Booster Dose, Christina A Rostad, Carol Kao, Et Al.

2020-Current year OA Pubs

Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.S. adults and evaluated the safety, reactogenicity and immunogenicity of homologous and heterologous MVA-BN®-Filo and Ad26.ZEBOV prime-boost schedules followed in select arms by MVA-BN®-Filo boost at 1 year (NCT02891980). We found that all vaccine regimens had acceptable safety and reactogenicity. The heterologous prime-boost strategy elicited superior Ebola binding and neutralizing antibody, antibody-dependent cellular cytotoxicity …

Bile Acids In Inflammatory Bowel Disease: From Pathophysiology To Treatment, Samantha H Bai, Arun Chandnani, Siyan Cao

2020-Current year OA Pubs

Inflammatory bowel disease (IBD) is a chronic condition that affects about 7 million people worldwide, and new therapies are needed. Understanding the complex roles that bile acids (BAs) play in IBD may lead to the development of novel IBD treatments independent of direct immunosuppression. This review discusses the latest discoveries in the roles BAs play in IBD pathogenesis and explores how these discoveries offer promising new therapeutic targets to treat IBD and improve patient outcomes. Several therapies discussed include specific BA receptor (BAR) agonists, dietary therapies, supplements, probiotics, and mesenchymal stem cell therapies that have all been shown to decrease …

The Plasmodium Falciparum Ncr1 Transporter Is An Antimalarial Target That Exports Cholesterol From The Parasite's Plasma Membrane, Zhemin Zhang, Eva S Istvan, Daniel E Goldberg, Et Al.

2020-Current year OA Pubs

Malaria, a devastating parasitic infection, is the leading cause of death in many developing countries. Unfortunately, the most deadliest causative agent of malaria,

Regional Differences In Three-Dimensional Fiber Organization, Smooth Muscle Cell Phenotype, And Contractility In The Pregnant Mouse Cervix, Christopher J Hansen, Christine M O'Brien, Et Al.

2020-Current year OA Pubs

The orientation and function of smooth muscle in the cervix may contribute to the important biomechanical properties that change during pregnancy. Thus, this study examined the three-dimensional structure, smooth muscle phenotype, and mechanical and contractile functions of the upper and lower cervix of nongravid (not pregnant) and gravid (pregnant) mice. In gravid cervix, we uncovered region-specific changes in the structure and organization of fiber tracts. We also detected a greater proportion of contractile smooth muscle cells (SMCs), but an equal proportion of synthetic SMCs, in the upper versus lower cervix. Furthermore, we revealed that the lower cervix had infrequent spontaneous …

Retrospective Derivation Of A Causal Pathway For Diabetic Ketoacidosis In Adult Patients With Type 2 Diabetes Mellitus, Jeffrey A Kline, Nicholas A Wesner, Amina T Sharif, Richard T Griffey, Phillip D Levy, Robert D Welch, George Grunberger

2020-Current year OA Pubs

BACKGROUND: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

RESEARCH DESIGN AND METHODS: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) …

Ifrd1 Is Required For Maintenance Of Bladder Epithelial Homeostasis, Bisiayo E Fashemi, Amala K Rougeau, Arnold M Salazar, Steven J Bark, Rayvanth Chappidi, Jeffrey W Brown, Charles J Cho, Jason C Mills, Indira U Mysorekar

2020-Current year OA Pubs

The maintenance of homeostasis and rapid regeneration of the urothelium following stress are critical for bladder function. Here, we identify a key role for IFRD1 in maintaining urothelial homeostasis in a mouse model. We demonstrate that the murine bladder expresses IFRD1 at homeostasis, particularly in the urothelium, and its loss alters the global transcriptome with significant accumulation of endolysosomes and dysregulated uroplakin expression pattern. We show that IFRD1 interacts with mRNA-translation-regulating factors in human urothelial cells. Loss of

Protocol For A Non-Surgical Model Of Perineural Invasion For Assessing Neural Drivers Of Cancer Aggressiveness In Mice, Tiago H Zaninelli, Telma Saraiva-Santos, Brielle H Patlin, Michael Slade Stratton, David Y Chen, Felipe A Pinho-Ribeiro

2020-Current year OA Pubs

Perineural invasion (PNI) is a significant risk factor for cancer recurrence and metastasis; however, its mechanisms relating to cancer aggressiveness remain poorly understood. Here, we present a protocol for a non-surgical model of PNI in mice using a neurotropic melanoma cell line that migrates from the skin to the sciatic nerve. We describe the steps for cell culture and injection, tumor burden measurements, mouse euthanasia, and tissue dissection. We then detail procedures for sample cross-section and confocal imaging.

Pancreaticoduodenectomy In Trauma Patients With Grade Iv-V Duodenal Or Pancreatic Injuries: A Post Hoc Analysis Of An East Multicenter Trial, Rachel Leah Choron, Rami Al-Aref, Jordan Michael Kirsch, Et Al.

2020-Current year OA Pubs

INTRODUCTION: The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV-V pancreaticoduodenal injuries.

METHODS: This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020. Included patients were ≥15 years of age with the American Association for the Surgery of Trauma grade IV-V duodenal and/or pancreatic injuries. The study compared operative repair strategy: PD versus non-PD.

RESULTS: The sample (n=95) was young (26 years), male (82%), …

The Effect Of A Low-Carbohydrate Diet On Evoked Pain And Quality Of Life In Non-Hispanic Black Women With Knee Osteoarthritis: A Pilot Study, Asia M Wiggins, Larissa J Strath, Gray E Mcpherson, Barbara A Gower, Amy M Goss, Burel R Goodin, Robert E Sorge

2020-Current year OA Pubs

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent chronic pain condition that can significantly impact quality of life and contribute to recognized chronic pain racial disparities. We have shown that a low-carbohydrate diet (LCD) can reduce KOA-related pain. Our previous work suggested that the LCD was more beneficial for women and non-Hispanic Black (NHB) adults, but our sample was not sufficiently diverse. Thus, we sought to determine whether the LCD may be beneficial for NHB women with KOA on measures of self-reported and evoked pain.

METHODS: Fourteen NHB women (M = 55.93, S.D. = 7.79 years of age) with KOA were …

Multimodal Oculomotor Assessment Reveals Prodromal Markers Of Parkinson's Disease In Non-Manifesting Lrrk2 G2019s Mutation Carriers, Heidi C Riek, Naomi P Visanji, Isabell C Pitigoi, Daniel G Di Luca, Laura Armengou-Garcia, Nazish Ahmed, Julia E Perkins, Donald C Brien, Jeff Huang, Brian C Coe, Jana Huang, Taneera Ghate, Anthony E Lang, Connie Marras, Douglas P Munoz

2020-Current year OA Pubs

Oculomotor behaviour changes in patients with Parkinson's disease (PD) are a promising source of prodromal disease markers. Capitalizing on this phenomenon to facilitate early diagnosis requires oculomotor assessment in prodromal cohorts. We examined oculomotor behaviour in non-manifesting LRRK2 G2019S mutation carriers (LRRK2-NM), who have heightened PD risk.Seventeen LRRK2-NM participants, 47 patients with idiopathic PD, and 63 healthy age-matched control participants completed an interleaved pro- and antisaccade task while undergoing video-based eye-tracking. We analyzed between-group differences in saccade, pupil, blink, and fixation acquisition behaviour. Patients with PD showed previously demonstrated abnormalities (saccade hypometria, antisaccade errors). Relative to controls, LRRK2-NM participants and …

Pediatric Providers' Views On Participating In An Hpv Vaccine Quality Improvement Intervention: A Qualitative Analysis, Edan Leshem, Sara Malone, Andrew Solsrud, Sherry Dodd, Shannon Rook, Sharon Graham, Lauren Ericson, Ruoyun Wang, Katie Plax, Jason Newland

2020-Current year OA Pubs

BACKGROUND: Human papillomavirus (HPV), a common sexually transmitted infection in the US, contributes to oropharyngeal and urogenital cancers. To improve HPV vaccine uptake, quality improvement (QI) interventions that address barriers to vaccination in primary care may help. This study aims to understand pediatric primary care providers' (PCP) perspectives on participating in an HPV QI intervention that utilized practice facilitation to improve HPV vaccine uptake in pediatric primary care clinics.

METHODS: Participants were pediatric PCPs whose clinics completed a QI intervention that utilized practice facilitation led by an outside facilitator. One PCP from each practice completed a 15-min semi-structured exit interview. …

Brain Volumes, Cognitive, And Adaptive Skills In School-Age Children With Down Syndrome, Rebecca Grzadzinski, Kelly Botteron, Natasha Marrus, Robert Mckinstry, Et Al.

2020-Current year OA Pubs

BACKGROUND: Down syndrome (DS) is the most common congenital neurodevelopmental disorder, present in about 1 in every 700 live births. Despite its prevalence, literature exploring the neurobiology underlying DS and how this neurobiology is related to behavior is limited. This study fills this gap by examining cortical volumes and behavioral correlates in school-age children with DS.

METHODS: School-age children (mean = 9.7 years ± 1.1) underwent comprehensive assessments, including cognitive and adaptive assessments, as well as an MRI scan without the use of sedation. Children with DS (n = 35) were compared to available samples of typically developing (TD; n …

Addressing Lung Truncation In 99mtc-Maa Spect/Ct For 90y Microsphere Radioembolization Treatment Planning, M Allan Thomas, Richard Laforest, John Karageorgiou, Dan Giardina, Tyler J Fraum, Chris D Malone, Justin K Mikell

2020-Current year OA Pubs

BACKGROUND: Prior studies have established that macroaggregated albumin (MAA)-SPECT/CT offers more robust lung shunt fraction (LSF) and lung mean absorbed dose (LMD) estimates in

METHODS: Lung truncation was simulated in 56 cases with adequate (> 90%, mean: 98%) lung coverage in MAA-SPECT/CT by removing slices in ~ 5 mm increments from the lung apices to the diaphragm. A wide range of lung coverages from 100% to <  1% in ~ 2% increments were created. LSF and LMD were calculated with four methods. (1) 2D planar imaging standard (not truncated), truncated lung SPECT/CT data was: (2) used with no corrections (SPECT

RESULTS: Averaged across simulated lung coverages from 40 to 80%, percent errors relative to non-truncated data for SPECT

CONCLUSION: LSF and LMD can be estimated for

M1 Recruitment During Interleaved Practice Is Important For Encoding, Not Just Consolidation, Of Skill Memory, Taewon Kim, Hakjoo Kim, Benjamin A Philip, David L Wright

2020-Current year OA Pubs

The primary motor cortex (M1) is crucial for motor skill learning. We examined its role in interleaved practice, which enhances retention (vs. repetitive practice) through M1-dependent consolidation. We hypothesized that cathodal transcranial direct current stimulation (ctDCS) to M1 would disrupt retention. We found that ctDCS reduced retention due to weakened encoding during acquisition, not disrupted consolidation. These results highlight M1's broad role in encoding and retention of novel motor skills.

Number Of Prescription Medications And Overall Survival In Metastatic Castrate-Resistant Prostate Cancer, Carley R Pickett, Daniel B Eaton, Krishny Karunanandaa, Emily Cybulla, Brendan T Heiden, Su-Hsin Chang, Yan Yan, Melanie P Subramanian, Varun Puri, Martin W Schoen

2020-Current year OA Pubs

No abstract provided.

Comparative Analysis Of Outcomes In Adult Spinal Deformity Patients With Proximal Junctional Kyphosis Or Failure Initially Fused To Upper Versus Lower Thoracic Spine, Oluwatobi O Onafowokan, Munish Chandra Gupta, Et Al.

2020-Current year OA Pubs

No abstract provided.

The Biomechanics Of Fibrillin Microfibrils: Lessons From The Ciliary Zonule, Pooja Rathaur, Juan Rodriguez, John Kuchtey, Samuel Insignares, Wendell B Jones, Rachel W Kuchtey, Steven Bassnett

2020-Current year OA Pubs

Marfan syndrome is an inherited connective tissue disorder that affects the cardiovascular, musculoskeletal, and ocular systems. It is caused by pathogenic variants in the fibrillin-1 gene (

Structural Variant Allelic Heterogeneity In Mecp2 Duplication Syndrome Provides Insight Into Clinical Severity And Variability Of Disease Expression, Davut Pehlivan, Marwan S Shinawi, Et Al.

2020-Current year OA Pubs

BACKGROUND: MECP2 Duplication Syndrome, also known as X-linked intellectual developmental disorder Lubs type (MRXSL; MIM: 300260), is a neurodevelopmental disorder caused by copy number gains spanning MECP2. Despite varying genomic rearrangement structures, including duplications and triplications, and a wide range of duplication sizes, no clear correlation exists between DNA rearrangement and clinical features. We had previously demonstrated that up to 38% of MRXSL families are characterized by complex genomic rearrangements (CGRs) of intermediate complexity (2 ≤ copy number variant breakpoints <  5), yet the impact of these genomic structures on regulation of gene expression and phenotypic manifestations have not been investigated.

METHODS: To study the role of the genomic rearrangement structures on an individual's clinical phenotypic variability, we employed a comprehensive …

Microglial Cd2ap Deficiency Exerts Protection In An Alzheimer's Disease Model Of Amyloidosis, Lingliang Zhang, David M. Holtzman, Et Al.

2020-Current year OA Pubs

BACKGROUND: The CD2-associated protein (CD2AP) was initially identified in peripheral immune cells and regulates cytoskeleton and protein trafficking. Single nucleotide polymorphisms (SNPs) in the CD2AP gene have been associated with Alzheimer's disease (AD). However, the functional role of CD2AP, especially its role in microglia during AD onset, remains elusive.

METHODS: CD2AP protein levels in cultured primary cells and in 5xFAD mice was studied. Microglial CD2AP-deficient mice were crossed with 5xFAD mice and the offspring were subjected to neuropathological assessment, behavioral tests, electrophysiology, RNA-seq, Golgi staining, and biochemistry analysis. Primary microglia were also isolated for assessing their uptake and morphology changes. …

Momordicine-I Suppresses Head And Neck Cancer Growth By Modulating Key Metabolic Pathways, Debojyoty Bandyopadhyay, Ellen T Tran, Ruchi A Patel, Matthew A Luetzen, Kevin Cho, Leah P Shriver, Gary J Patti, Mark A Varvares, David A Ford, Kyle S Mccommis, Ratna B Ray

2020-Current year OA Pubs

One of the hallmarks of cancer is metabolic reprogramming which controls cellular homeostasis and therapy resistance. Here, we investigated the effect of momordicine-I (M-I), a key bioactive compound from Momordica charantia (bitter melon), on metabolic pathways in human head and neck cancer (HNC) cells and a mouse HNC tumorigenicity model. We found that M-I treatment on HNC cells significantly reduced the expression of key glycolytic molecules, SLC2A1 (GLUT-1), HK1, PFKP, PDK3, PKM, and LDHA at the mRNA and protein levels. We further observed reduced lactate accumulation, suggesting glycolysis was perturbed in M-I treated HNC cells. Metabolomic analyses confirmed a marked …