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2023

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Full-Text Articles in Medical Specialties

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz Oct 2023

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods We treated hAPP mice with …


Regulated Translocation Of Neutral Sphingomyelinase-2 To The Plasma Membrane Drives Insulin Resistance In Steatotic Hepatocytes, Salim S. El-Amouri, Alexander A. Karakashian, Erhard Bieberich, Mariana N. Nikolova‑Karakashian Oct 2023

Regulated Translocation Of Neutral Sphingomyelinase-2 To The Plasma Membrane Drives Insulin Resistance In Steatotic Hepatocytes, Salim S. El-Amouri, Alexander A. Karakashian, Erhard Bieberich, Mariana N. Nikolova‑Karakashian

Markey Cancer Center Faculty Publications

Abstract Obesity-associated diabetes is linked to the accumulation of ceramide in various organs, including the liver. The exact mechanisms by which ceramide contributes to diabetic pathology are unclear, but one proposed scenario is that ceramide accumulation may inhibit insulin signaling pathways. It is unknown however whether the excess ceramide is generated proximal to the insulin receptor, that is, at the plasma membrane (PM), where it could affect the insulin signaling pathway directly, or the onset of insulin resistance is due to ceramide- induced mitochondrial dysfunction and/or lipotoxicity. Using hepatic cell lines and primary cultures, gain- and loss- of function approach, …


Rit1 Regulation Of Cns Lipids Rit1 Deficiency Alters Cerebral Lipid Metabolism And Reduces White Matter Tract Oligodendrocytes And Conduction Velocities, Lei Wu, Fang Wang, Carole L. Moncman, Mritunjay Pandey, Harrison A. Clarke, Hilaree N. Frazier, Lyndsay E. A. Young, Matthew S. Gentry, Weikang Cai, Olivier Thibault, Ramon C. Sun, Douglas A. Andres Oct 2023

Rit1 Regulation Of Cns Lipids Rit1 Deficiency Alters Cerebral Lipid Metabolism And Reduces White Matter Tract Oligodendrocytes And Conduction Velocities, Lei Wu, Fang Wang, Carole L. Moncman, Mritunjay Pandey, Harrison A. Clarke, Hilaree N. Frazier, Lyndsay E. A. Young, Matthew S. Gentry, Weikang Cai, Olivier Thibault, Ramon C. Sun, Douglas A. Andres

Markey Cancer Center Faculty Publications

Oligodendrocytes (OLs) generate lipid-rich myelin membranes that wrap axons to enable efficient transmission of electrical impulses. Using a RIT1 knockout mouse model and in situ high- resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) coupled with MS-based lipidomic analysis to determine the contribution of RIT1 to lipid homeostasis. Here, we report that RIT1 loss is associated with altered lipid levels in the central nervous system (CNS), including myelin-associated lipids within the corpus callosum (CC). Perturbed lipid metabolism was correlated with reduced numbers of OLs, but increased numbers of GFAP+ glia, in the CC, but not in grey matter. This was …


Stat3 Modulates Cd4+ T Mitochondrial Dynamics And Function In Aging, Emelia Zukowski, Marco Sannella, Jack Donato Rockhold, Gabriella Kalantar, Jingting Yu, Sara Santacruz-Calvo, Madison K. Kuhn, Nasun Hah, Ling Ouyang, Tzu-Wen Wang, Lyanne Murphy, Heather Marszalkowski, Kaleigh Gibney, Micah J. Drummond, Elizabeth A. Proctor, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath Oct 2023

Stat3 Modulates Cd4+ T Mitochondrial Dynamics And Function In Aging, Emelia Zukowski, Marco Sannella, Jack Donato Rockhold, Gabriella Kalantar, Jingting Yu, Sara Santacruz-Calvo, Madison K. Kuhn, Nasun Hah, Ling Ouyang, Tzu-Wen Wang, Lyanne Murphy, Heather Marszalkowski, Kaleigh Gibney, Micah J. Drummond, Elizabeth A. Proctor, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Markey Cancer Center Faculty Publications

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and …


Impact Of Fetal Health Center On Mode Of Neonatal Death, Erin Bolen, Ashley Sherman, Julie Weiner, Jotishna Sharma Oct 2023

Impact Of Fetal Health Center On Mode Of Neonatal Death, Erin Bolen, Ashley Sherman, Julie Weiner, Jotishna Sharma

Posters

Introduction There has been significant innovation and technological advancement in prenatal diagnosis, fetal therapeutic intervention, and establishment of fetal health centers (FHC) at children’s hospitals with dedicated delivery services for high-risk neonates and expedited access to level IV neonatal intensive care units (NICU). Morality trends have been examined on individual bases and within diagnostic groups, but there have been few studies that examine overall modes of mortality in the NICU population across diagnoses after the implementation of a dedicated FHC. This study aims to compare modes of death at a level IV children’s hospital NICU between infants born at the …


Latency Time From Prior Authorization Submission To Initiation Of Biologic Therapy In Inflammatory Bowel Disease, Shannon Capraro, Janelle R. Noel-Macdonnell Phd, Lauren Disselhoff, Layne Sieve, Rachel Chevalier Oct 2023

Latency Time From Prior Authorization Submission To Initiation Of Biologic Therapy In Inflammatory Bowel Disease, Shannon Capraro, Janelle R. Noel-Macdonnell Phd, Lauren Disselhoff, Layne Sieve, Rachel Chevalier

Posters

Background For pediatric patients with a diagnosis of inflammatory bowel disease (IBD), initiation of biologic therapy can be essential to attain disease control. Unfortunately, patients often experience delays in receiving the first dose of these medications due to the need for insurance companies to approve medication prior authorizations (PA). Physicians and support staff spend many working hours collating and transferring information regarding urgency to payors. To our knowledge, no studies exist to evaluate the factors that contribute to how quickly a medication is approved in pediatric patients. We set out here to evaluate which demographic and disease factors contribute to …


Life Threatening Anemia And Acidosis Secondary To Systemic Loxoscelism In A Pediatric Patient, Rohan Akhouri, Vincent J. Calleo, Leslie Hueschen Oct 2023

Life Threatening Anemia And Acidosis Secondary To Systemic Loxoscelism In A Pediatric Patient, Rohan Akhouri, Vincent J. Calleo, Leslie Hueschen

Posters

Introduction Rashes are common in pediatric patients and most resolve without significant patient illness. In rare cases, they can represent life-threatening disease entities. History is crucial to determine a rash’s etiology, and barriers like developmental delay and language can complicate accurate diagnosis. We present a case of hemodynamic instability and hemolysis without known envenomation, which was diagnosed as systemic loxoscelism. Case Description A 10-year-old male with developmental delay presented with decreased activity and reduced oral intake for 4 days. An interpreter was used due to a language barrier. Initial vital signs were T 36.6°C, HR=120, RR=20, BP=117/66, and SpO2 96%. …


National Prescribing Practices For Dystonia Among Providers In The United States, Sarah Paige Davis, Natalie J. Kane, Haley Botteron, Rose N. Gelineau-Morel Oct 2023

National Prescribing Practices For Dystonia Among Providers In The United States, Sarah Paige Davis, Natalie J. Kane, Haley Botteron, Rose N. Gelineau-Morel

Posters

Objective: While multiple oral medications are used to treat dystonia, limited information exists on current prescribing practices. This study analyzes prescribing practices for dystonia in the United States, evaluating variations in dosing and impact of co-morbidities. Methods: Querying the Cerner Real World database from 2014 to 2019 for children age 0-18 with an ICD-10 diagnosis containing “dystonia” resulted in 11,300 inpatient and outpatient encounters. Information extracted included current dystonia medications (baclofen, clonidine, carbidopa-levodopa, gabapentin, tetrabenazine, trihexyphenidyl, and benzodiazepines including diazepam, clonazepam, midazolam, and lorazepam), medication dosing, and co-morbid diagnoses of cerebral palsy, epilepsy, or spasticity. Encounters without current weight were …


Distinguishing Dystrophic Calcification From Calciphylaxis, Elizabeth Jones, Alexander Valiga, Miriam Solowey Oct 2023

Distinguishing Dystrophic Calcification From Calciphylaxis, Elizabeth Jones, Alexander Valiga, Miriam Solowey

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

Calcinosis cutis, a disorder in which calcium salts deposit in skin and subcutis, is categorized into five subtypes: dystrophic calcification, metastatic calcification, idiopathic calcification, iatrogenic calcification, and calciphylaxis.

Dystrophic calcification, the most common subtype, typically results from local tissue damage1,2 and is proposed to be caused by the release of phosphate binding proteins by necrotic cells in response to tissue damage, inflammation, or hypoxia.2 The condition often presents with nontender nodules of the skin or subcutis and normal serum calcium.

Calciphylaxis is believed to be caused by impaired inhibition of calcification in the microvasculature.3 …


An Unusual Presentation Of Pigmented Purpuric Lichenoid Dermatitis, Christine De Antonis, Jordan T. Hyde, Jason B. Lee, Sylvia Hsu Oct 2023

An Unusual Presentation Of Pigmented Purpuric Lichenoid Dermatitis, Christine De Antonis, Jordan T. Hyde, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

Pigmented purpuric lichenoid dermatitis (PPLD) is a rare subtype of pigmented purpuric dermatosis, which classically presents with a mixture of lichenoid papules and patches on the bilateral lower extremities. Herein, we describe an unusual case of a 47-year-old man with PPLD who presented with 1-3mm discrete papules without the presence of larger patches. The diagnosis of PPLD should be considered for patients presenting with bilateral symmetric discrete papules on the legs.


Perforated Pre-Pyloric Ulcer In The Gastric Remnant Over A Decade After Roux-En-Y Gastric Bypass: A Case Report, Bianca Marquez, Emmanuel Luciano, Ryan Cohen, Christina Maser, Matthew Hubbard Oct 2023

Perforated Pre-Pyloric Ulcer In The Gastric Remnant Over A Decade After Roux-En-Y Gastric Bypass: A Case Report, Bianca Marquez, Emmanuel Luciano, Ryan Cohen, Christina Maser, Matthew Hubbard

Einstein Health Papers

INTRODUCTION AND IMPORTANCE: Roux-en-Y gastric bypass (RYGB) is one of the two most common weight loss surgeries. Surgical emergencies after gastric bypass can be complicated by devastating events that are often difficult to diagnose and manage. Perforated ulcers are a very rare complication after a RYGB.

CASE PRESENTATION: In this report, the diagnosis and surgical management of a 59-year-old immunosuppressed male patient who presented with late perforation of a pre-pyloric ulcer in the gastric remnant after RYGB is presented. The perforation was repaired transversely in a running horizontal mattress fashion and patched with a piece of well-vascularized omentum.

CLINICAL DISCUSSION: …


Ignoring Clustering And Nesting Effects Are Invalid Analysis Choices In A Trial With Clustered Data In Trials Testing Causal Effects Re: "Impact Of A Montessori-Based Nutrition Program On Children's Knowledge And Eating Behaviors", Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Colby J Vorland, Abu Bakkar Siddique, Deborah H Glueck, David B Allison Oct 2023

Ignoring Clustering And Nesting Effects Are Invalid Analysis Choices In A Trial With Clustered Data In Trials Testing Causal Effects Re: "Impact Of A Montessori-Based Nutrition Program On Children's Knowledge And Eating Behaviors", Yasaman Jamshidi-Naeini, Lilian Golzarri-Arroyo, Colby J Vorland, Abu Bakkar Siddique, Deborah H Glueck, David B Allison

Children’s Nutrition Research Center Staff Publications

Vitale and Coccia conducted a study to examine the effects of a nutrition education program among school children, and reported statistically significant between-group effects for nutrition knowledge and liking tomatoes. In the study blocks of classrooms were assigned to the study conditions. Thus, with children nested within classrooms, and classrooms nested within blocks, the study has a two-level design, and block is the independent sampling unit. The analysis of the study must account for the two levels of clustering, but it did not. This render the conclusions reported in the paper unsubstantiated. For correcting the scientific record, reanalysis of the …


Inaccurate Confidence Intervals Reported In “The Healthy Kids & Families Study: Outcomes Of A 24-Month Childhood Obesity Prevention Intervention”, Xingsheng Li, Abu Bakkar Siddique, Lilian Golzarri-Arroyo, Stephanie L Dickinson, Theodore K Kyle, David B Allison Oct 2023

Inaccurate Confidence Intervals Reported In “The Healthy Kids & Families Study: Outcomes Of A 24-Month Childhood Obesity Prevention Intervention”, Xingsheng Li, Abu Bakkar Siddique, Lilian Golzarri-Arroyo, Stephanie L Dickinson, Theodore K Kyle, David B Allison

Children’s Nutrition Research Center Staff Publications

No abstract provided.


Expert Panel Curation Of 113 Primary Mitochondrial Disease Genes For The Leigh Syndrome Spectrum, Elizabeth M Mccormick, Kierstin Keller, Julie P Taylor, Alison J Coffey, Lishuang Shen, Danuta Krotoski, Brian Harding, Xiaowu Gai, Marni J Falk, Zarazuela Zolkipli-Cunningham, Shamima Rahman Oct 2023

Expert Panel Curation Of 113 Primary Mitochondrial Disease Genes For The Leigh Syndrome Spectrum, Elizabeth M Mccormick, Kierstin Keller, Julie P Taylor, Alison J Coffey, Lishuang Shen, Danuta Krotoski, Brian Harding, Xiaowu Gai, Marni J Falk, Zarazuela Zolkipli-Cunningham, Shamima Rahman

Children’s Nutrition Research Center Staff Publications

Objective: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes.

Methods: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP …


Does Spasticity Correlate With Motor Impairment In The Upper And Lower Limbs In Ambulatory Chronic Stroke Survivors??, Sheng Li, Jaskiran Ghuman, Javier Gonzalez-Buonomo, Xinran Huang, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Hulin Wu, Walter R Frontera Oct 2023

Does Spasticity Correlate With Motor Impairment In The Upper And Lower Limbs In Ambulatory Chronic Stroke Survivors??, Sheng Li, Jaskiran Ghuman, Javier Gonzalez-Buonomo, Xinran Huang, Aila Malik, Nuray Yozbatiran, Gerard E Francisco, Hulin Wu, Walter R Frontera

Faculty, Staff and Student Publications

OBJECTIVE: This study aimed to explore correlations between spasticity and motor impairments in the upper and lower limbs in ambulatory chronic stroke survivors.

DESIGN: We performed clinical assessments in 28 ambulatory chronic stroke survivors with spastic hemiplegia (female: 12; male: 16; mean ages = 57.8 ± 11.8 yrs; 76 ± 45 mos after stroke).

RESULTS: In the upper limb, spasticity index and Fugl-Meyer Motor Assessment showed a significant correlation. Spasticity index for the upper limb showed a significant negative correlation with handgrip strength of the affected side ( r = -0.4, P = 0.035) while Fugl-Meyer Motor Assessment for the …


Reducing The Rate Of Central Line-Associated Bloodstream Infections; A Quality Improvement Project, David Odada, Hellen Munyi, Japhet Gatuiku, Ruth Thuku, Jared Nyandigisi, Anne Wangui, Emilie Ashihundu, Beatrice Nyakiringa, Jemimah Kimeu, Martin Musumbi, Rodney Adam Oct 2023

Reducing The Rate Of Central Line-Associated Bloodstream Infections; A Quality Improvement Project, David Odada, Hellen Munyi, Japhet Gatuiku, Ruth Thuku, Jared Nyandigisi, Anne Wangui, Emilie Ashihundu, Beatrice Nyakiringa, Jemimah Kimeu, Martin Musumbi, Rodney Adam

Internal Medicine, East Africa

Background The burden of central line-associated bloodstream infections is significant and has negative implications for healthcare, increasing morbidity and mortality risks, increasing inpatient hospital stays, and increasing the cost of hospitalization. Efforts to reduce the incidence of central line-associated bloodstream infections have utilized quality improvement projects that implement, measure, and monitor outcomes. However, variations in location, healthcare organization, patient risks, and practice gaps are key to the success of interventions and approaches. This study aims to evaluate interventions of a quality improvement project on the reduction of central line-associated bloodstream infection rates at a university teaching hospital.

Methods This was …


Response To "Point-Of-Care Ultrasound And Procedural Instruction In The Family Medicine Clerkship: A Cera Study"., Kennedy Ovenseri Oct 2023

Response To "Point-Of-Care Ultrasound And Procedural Instruction In The Family Medicine Clerkship: A Cera Study"., Kennedy Ovenseri

Medical Education Articles

No abstract provided.


Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent Oct 2023

Longitudinal Associations Between Cognitive Functioning And Depressive Symptoms Among Couples In The Mexican Health And Aging Study, Joan K Monin, Gail Mcavay, Katie Newkirk, Rafael Samper-Ternent

Faculty, Staff and Student Publications

OBJECTIVE: To examine the bidirectional associations between older adult spouses' cognitive functioning and depressive symptoms over time and replicate previous findings from the United States (US) in Mexico.

DESIGN: Longitudinal, dyadic path analysis with the actor-partner interdependence model.

SETTING: Data were from the three most recent interview waves (2012, 2015, and 2018) of the Mexican Health and Aging Study (MHAS), a longitudinal national study of adults aged 50+ years in Mexico.

PARTICIPANTS: Husbands and wives from 905 community-dwelling married couples (N = 1,810).

MEASUREMENTS: The MHAS cognitive battery measured cognitive function. Depressive symptoms were assessed using a modified nine-item Center …


Serum Metabolomic Markers Of Dairy Consumption: Results From The Atherosclerosis Risk In Communities Study And The Bogalusa Heart Study, Lauren Bernard, Jingsha Chen, Hyunju Kim, Zhijie Huang, Lydia Bazzano, Lu Qi, Jiang He, Varun S Rao, Kaitlin S Potts, Tanika N Kelly, Kari E Wong, Lyn M Steffen, Bing Yu, Eugene P Rhee, Casey M Rebholz Oct 2023

Serum Metabolomic Markers Of Dairy Consumption: Results From The Atherosclerosis Risk In Communities Study And The Bogalusa Heart Study, Lauren Bernard, Jingsha Chen, Hyunju Kim, Zhijie Huang, Lydia Bazzano, Lu Qi, Jiang He, Varun S Rao, Kaitlin S Potts, Tanika N Kelly, Kari E Wong, Lyn M Steffen, Bing Yu, Eugene P Rhee, Casey M Rebholz

Faculty, Staff and Student Publications

BACKGROUND: Dairy consumption is related to chronic disease risk; however, the measurement of dairy consumption has largely relied upon self-report. Untargeted metabolomics allows for the identification of objective markers of dietary intake.

OBJECTIVES: We aimed to identify associations between dietary dairy intake (total dairy, low-fat dairy, and high-fat dairy) and serum metabolites in 2 independent study populations of United States adults.

METHODS: Dietary intake was assessed with food frequency questionnaires. Multivariable linear regression models were used to estimate cross-sectional associations between dietary intake of dairy and 360 serum metabolites analyzed in 2 subgroups of the Atherosclerosis Risk in Communities study …


Pirh2-Dependent Dna Damage In Neurons Induced By The G-Quadruplex Ligand Pyridostatin, Rocio Diaz Escarcega, Abhijeet A Patil, Jose F Moruno-Manchon, Akihiko Urayama, Sean P Marrelli, Nayun Kim, David Monchaud, Louise D Mccullough, Andrey S Tsvetkov Oct 2023

Pirh2-Dependent Dna Damage In Neurons Induced By The G-Quadruplex Ligand Pyridostatin, Rocio Diaz Escarcega, Abhijeet A Patil, Jose F Moruno-Manchon, Akihiko Urayama, Sean P Marrelli, Nayun Kim, David Monchaud, Louise D Mccullough, Andrey S Tsvetkov

Faculty, Staff and Student Publications

Noncanonical base pairing between four guanines (G) within single-stranded G-rich sequences leads to formation of а G-quartet. Self-stacking of G-quartets results in a columnar four-stranded DNA structure known as the G-quadruplex (G4 or G4-DNA). In cancer cells, G4-DNA regulates multiple DNA-dependent processes, including transcription, replication, and telomere function. How G4s function in neurons is poorly understood. Here, we performed a genome-wide gene expression analysis (RNA-Seq) to identify genes modulated by a G4-DNA ligand, pyridostatin (PDS), in primary cultured neurons. PDS promotes stabilization of G4 structures, thus allowing us to define genes directly or indirectly responsive to G4 regulation. We found …


Dimensionality Reduction For Improving Out-Of-Distribution Detection In Medical Image Segmentation, Mckell Woodland, Nihil Patel, Mais Al Taie, Joshua P Yung, Tucker J Netherton, Ankit B Patel, Kristy K Brock Oct 2023

Dimensionality Reduction For Improving Out-Of-Distribution Detection In Medical Image Segmentation, Mckell Woodland, Nihil Patel, Mais Al Taie, Joshua P Yung, Tucker J Netherton, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

Clinically-deployed deep learning-based segmentation models are known to fail on data outside of their training distributions. While clinicians review the segmentations, these models do tend to perform well in most instances, which could exacerbate automation bias. Therefore, it is critical to detect out-of-distribution images at inference to warn the clinicians that the model likely failed. This work applies the Mahalanobis distance post hoc to the bottleneck features of a Swin UNETR model that segments the liver on T1-weighted magnetic resonance imaging. By reducing the dimensions of the bottleneck features with principal component analysis, images the model failed on were detected …


Lowering Of Circulating Sclerostin May Increase Risk Of Atherosclerosis And Its Risk Factors: Evidence From A Genome-Wide Association Meta-Analysis Followed By Mendelian Randomization, Jie Zheng, Eleanor Wheeler, Maik Pietzner, Till F M Andlauer, Michelle S Yau, April E Hartley, Ben Michael Brumpton, Humaira Rasheed, John P Kemp, Monika Frysz, Jamie Robinson, Sjur Reppe, Vid Prijatelj, Kaare M Gautvik, Louise Falk, Winfried Maerz, Ingrid Gergei, Patricia A Peyser, Maryam Kavousi, Paul S De Vries, Clint L Miller, Maxime Bos, Sander W Van Der Laan, Rajeev Malhotra, Markus Herrmann, Hubert Scharnagl, Marcus Kleber, George Dedoussis, Eleftheria Zeggini, Maria Nethander, Claes Ohlsson, Mattias Lorentzon, Nick Wareham, Claudia Langenberg, Michael V Holmes, George Davey Smith, Jonathan H Tobias Oct 2023

Lowering Of Circulating Sclerostin May Increase Risk Of Atherosclerosis And Its Risk Factors: Evidence From A Genome-Wide Association Meta-Analysis Followed By Mendelian Randomization, Jie Zheng, Eleanor Wheeler, Maik Pietzner, Till F M Andlauer, Michelle S Yau, April E Hartley, Ben Michael Brumpton, Humaira Rasheed, John P Kemp, Monika Frysz, Jamie Robinson, Sjur Reppe, Vid Prijatelj, Kaare M Gautvik, Louise Falk, Winfried Maerz, Ingrid Gergei, Patricia A Peyser, Maryam Kavousi, Paul S De Vries, Clint L Miller, Maxime Bos, Sander W Van Der Laan, Rajeev Malhotra, Markus Herrmann, Hubert Scharnagl, Marcus Kleber, George Dedoussis, Eleftheria Zeggini, Maria Nethander, Claes Ohlsson, Mattias Lorentzon, Nick Wareham, Claudia Langenberg, Michael V Holmes, George Davey Smith, Jonathan H Tobias

Faculty, Staff and Student Publications

OBJECTIVE: In this study, we aimed to establish the causal effects of lowering sclerostin, target of the antiosteoporosis drug romosozumab, on atherosclerosis and its risk factors.

METHODS: A genome-wide association study meta-analysis was performed of circulating sclerostin levels in 33,961 European individuals. Mendelian randomization (MR) was used to predict the causal effects of sclerostin lowering on 15 atherosclerosis-related diseases and risk factors.

RESULTS: We found that 18 conditionally independent variants were associated with circulating sclerostin. Of these, 1 cis signal in SOST and 3 trans signals in B4GALNT3, RIN3, and SERPINA1 regions showed directionally opposite signals for sclerostin levels and …


Metabolomic Signatures Of Sedentary Behavior And Cardiometabolic Traits In Us Hispanics/Latinos: Results From Hchs/Sol, Jee-Young Moon, Jin Choul Chai, Bing Yu, Rebecca J Song, Guo-Chong Chen, Mariaelisa Graff, Martha L Daviglus, Queenie Chan, Bharat Thyagarajan, Sheila F Castaneda, Megan L Grove, Jianwen Cai, Xiaonan Xue, Yasmin Mossavar-Rahmani, Ramachandran S Vasan, Eric Boerwinkle, Robert C Kaplan, Qibin Qi Oct 2023

Metabolomic Signatures Of Sedentary Behavior And Cardiometabolic Traits In Us Hispanics/Latinos: Results From Hchs/Sol, Jee-Young Moon, Jin Choul Chai, Bing Yu, Rebecca J Song, Guo-Chong Chen, Mariaelisa Graff, Martha L Daviglus, Queenie Chan, Bharat Thyagarajan, Sheila F Castaneda, Megan L Grove, Jianwen Cai, Xiaonan Xue, Yasmin Mossavar-Rahmani, Ramachandran S Vasan, Eric Boerwinkle, Robert C Kaplan, Qibin Qi

Faculty, Staff and Student Publications

PURPOSE: The aim of this study was to understand the serum metabolomic signatures of moderate-to-vigorous physical activity (MVPA) and sedentary behavior, and further associate their metabolomic signatures with incident cardiometabolic diseases.

METHODS: This analysis included 2711 US Hispanics/Latinos from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) aged 18-74 yr (2008-2011). An untargeted, liquid chromatography-mass spectrometry was used to profile the serum metabolome. The associations of metabolites with accelerometer-measured MVPA and sedentary time were examined using survey linear regressions adjusting for covariates. The weighted correlation network analysis identified modules of correlated metabolites in relation to sedentary time, and the modules …


Oral Pustular Lesions In The Setting Of Yersinia Enterocolitica Infection, Alberto D. Lopez Juarez, Kanisha Patel, Jordan Kishbaugh, Aaron Silva Oct 2023

Oral Pustular Lesions In The Setting Of Yersinia Enterocolitica Infection, Alberto D. Lopez Juarez, Kanisha Patel, Jordan Kishbaugh, Aaron Silva

School of Medicine Publications

Yersinia enterocolitica is a gram-negative, rod-shaped, pleomorphic bacteria that is a common source of infectious gastroenteritis. In the United States, Centers of Disease Control and Prevention note yearly 117,000 illnesses, 640 hospitalizations, and 35 deaths [1]. Termed Yersiniosis, the infection is most often acquired via fecal-oral transmission, with sources arising from contaminated pork and unpasteurized milk. Following the fecal-oral transmission, the pathogen invades the intestinal lumen and attaches to the brush border [2]. The clinical presentation includes low-grade fever, vomiting, and invasive diarrhea and further manifestations range from pseudoappendicitis and reactive arthritis [2-3]. Although well-known for its ability to cause …


Universal Health Coverage: A Basis For Pandemic Preparedness?, Merline Feero Oct 2023

Universal Health Coverage: A Basis For Pandemic Preparedness?, Merline Feero

Independent Study Project (ISP) Collection

Amid extensive research and reporting on the effects of COVID-19 on Universal Health Coverage (UHC) progress, this study explores an often neglected topic: the potential of UHC to contribute to the foundations of pandemic preparedness. Herein, quantitative analysis reveals that countries with higher UHC coverage tend to exhibit greater pandemic preparedness (as determined by the UHC Service Coverage Index and the Global Health Security Index). Complementary qualitative analysis is used to further illustrate and explain the correlation between UHC and pandemic preparedness using four case study countries, integrating literature reviews and relevant expert interviews. Through these methods, a clear tie …


The Global Survey Of Disease Burden And Stigma Among Patients With Nafld And Their Healthcare Providers, Zobair M. Younossi, Yusuf Yilmaz, Jian-Gao Fan, Ming-Hua Zheng, Khalid Aida Alswat, Saleh A. Alqahtani, Mohamed El-Kassas, Laurent Castera, Jesus Funuyet-Salas, Stuart C. Gordon Oct 2023

The Global Survey Of Disease Burden And Stigma Among Patients With Nafld And Their Healthcare Providers, Zobair M. Younossi, Yusuf Yilmaz, Jian-Gao Fan, Ming-Hua Zheng, Khalid Aida Alswat, Saleh A. Alqahtani, Mohamed El-Kassas, Laurent Castera, Jesus Funuyet-Salas, Stuart C. Gordon

Conference Presentation Abstracts

Background: NAFLD can be associated with disease burden and stigma to patients and providers. Aims: To understand the disease burden and stigma related to NAFLD. Methods: Members of the Global NASH Council created two surveys (68-item patient and 41- items provider survey) about experiences and attitudes toward NAFLD and related terms. Results: The surveys were completed by 895 NAFLD patients (19 countries) and 629 providers (64% GI/hepatologists, 23 countries). Of all patients, 64% ever disclosed having NAFLD to family/friends; the main term used was “fatty liver” (82%) while “metabolic disease” or “MAFLD” were rarely used (never by 88%). 35% of …


Persistent Pruritus Associated With Worse Quality Of Life In Patients With Chronic Hepatitis, Mei Lu, Lora Rupp, Christina Melkonian, Sheri Trudeau, Yihe G. Daida, Mark A. Schmidt, Stuart C. Gordon Oct 2023

Persistent Pruritus Associated With Worse Quality Of Life In Patients With Chronic Hepatitis, Mei Lu, Lora Rupp, Christina Melkonian, Sheri Trudeau, Yihe G. Daida, Mark A. Schmidt, Stuart C. Gordon

Conference Presentation Abstracts

Background: Pruritus—itching—is common with liver disease, but its prevalence and severity among US patients with chronic hepatitis B and C (HBV, HCV) are not well-documented. A subset of patients from the Chronic Hepatitis Cohort Study (CHeCS) were surveyed to examine pruritus prevalence, persistence, and management, and the impact on patients’ quality of life (QoL). Methods: The validated Pruritus Numeric Rating Scale (NRS) was used to assess pruritus intensity; patients who reported a score ≥ 3 in the last 30 days were invited to participate in a 6-month study using the validated SF-36 questionnaire. A general regression model (univariate followed by …


Predictors Of Coronary Artery Disease In Heart Failure With Reduced Ejection Fraction At The Aga Khan University Hospital In Nairobi, Redemptar Kimeu, Jeilan Mohamed, Mzee Ngunga Oct 2023

Predictors Of Coronary Artery Disease In Heart Failure With Reduced Ejection Fraction At The Aga Khan University Hospital In Nairobi, Redemptar Kimeu, Jeilan Mohamed, Mzee Ngunga

Internal Medicine, East Africa

There appears to be an epidemiological transition in the etiology of heart failure in sub-Saharan Africa (SSA) in parallel with a steady increase in risk factors for coronary artery disease (CAD). SSA has limited access to heart failure and CAD diagnostics, limiting the number of patients who receive optimal care. Our objectives were to study the predictors of coronary artery disease among patients with heart failure with reduced ejection fraction (HFrEF) and develop a model to assist clinicians in determining the likelihood of CAD before cardiac catheterization.

Methodology: This was a retrospective study at the Aga Khan University Hospital, …


Normative Spatiotemporal Fetal Brain Maturation With Satisfactory Development At 2 Years, Ana I. L. Namburete, Bartłomiej W. Papież, Michelle Fernandes, Madeleine K. Wyburd, Linde S. Hesse, Felipe A. Moser, Leila Cheikh Ismail, Robert B. Gunier, Waney Squier, Maria Carvalho Oct 2023

Normative Spatiotemporal Fetal Brain Maturation With Satisfactory Development At 2 Years, Ana I. L. Namburete, Bartłomiej W. Papież, Michelle Fernandes, Madeleine K. Wyburd, Linde S. Hesse, Felipe A. Moser, Leila Cheikh Ismail, Robert B. Gunier, Waney Squier, Maria Carvalho

Obstetrics and Gynaecology, East Africa

Maturation of the human fetal brain should follow precisely scheduled structural growth and folding of the cerebral cortex for optimal postnatal function1 . We present a normative digital atlas of fetal brain maturation based on a prospective international cohort of healthy pregnant women2 , selected using World Health Organization recommendations for growth standards3 . Their fetuses were accurately dated in the first trimester, with satisfactory growth and neurodevelopment from early pregnancy to 2 years of age4,5 . The atlas was produced using 1,059 optimal quality, three dimensional ultrasound brain volumes from 899 of the fetuses and an automated analysis pipeline6–8 …


Utilizing Speech Analysis To Differentiate Progressive Supranuclear Palsy From Parkinson’S Disease, Kyurim Kang, Adonay S Nunes, Mansi Sharma, A J Hall, Ram Kinker Mishra, Jose Casado, Rylee Cole, Marc Derhammer, Gregory Barchard, Bijan Najafi, Ashkan Vaziri, Anne-Marie Wills, Alexander Pantelyat Oct 2023

Utilizing Speech Analysis To Differentiate Progressive Supranuclear Palsy From Parkinson’S Disease, Kyurim Kang, Adonay S Nunes, Mansi Sharma, A J Hall, Ram Kinker Mishra, Jose Casado, Rylee Cole, Marc Derhammer, Gregory Barchard, Bijan Najafi, Ashkan Vaziri, Anne-Marie Wills, Alexander Pantelyat

Center on Aging Staff Publications

Introduction: Distinguishing Parkinson's disease (PD) from Progressive supranuclear palsy (PSP) at early disease stages is important for clinical trial enrollment and clinical care/prognostication.

Methods: We recruited 21 participants with PSP(n = 11) or PD(n = 10) with reliable caregivers. Standardized passage reading, counting, and sustained phonation were recorded on the BioDigit Home tablet (BioSensics LLC, Newton, MA USA), and speech features from the assessments were analyzed using the BioDigit Speech platform (BioSensics LLC, Newton, MA USA). An independent t-test was performed to compare each speech feature between PSP and PD participants. We also performed Spearman's correlations to evaluate associations between …