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P97/Vcp Is Highly Expressed In The Stem-Like Cells Of Breast Cancer And Controls Cancer Stemness Partly Through The Unfolded Protein Response, Chuang Li, Yongsheng Huang, Qianqian Fan, Hongyang Quan, Yeqing Dong, Meng Nie, Jiaqi Wang, Fucun Xie, Jiang Ji, Lan Zhou, Zhi Zheng, Lin Wang Mar 2021

P97/Vcp Is Highly Expressed In The Stem-Like Cells Of Breast Cancer And Controls Cancer Stemness Partly Through The Unfolded Protein Response, Chuang Li, Yongsheng Huang, Qianqian Fan, Hongyang Quan, Yeqing Dong, Meng Nie, Jiaqi Wang, Fucun Xie, Jiang Ji, Lan Zhou, Zhi Zheng, Lin Wang

2020-Current year OA Pubs

p97/VCP, an evolutionarily concerned ATPase, partakes in multiple cellular proteostatic processes, including the endoplasmic reticulum (ER)-associated protein degradation (ERAD). Elevated expression of p97 is common in many cancers and is often associated with poor survival. Here we report that the levels of p97 positively correlated with the histological grade, tumor size, and lymph node metastasis in breast cancers. We further examined p97 expression in the stem-like cancer cells or cancer stem cells (CSCs), a cell population that purportedly underscores cancer initiation, therapeutic resistance, and recurrence. We found that p97 was consistently at a higher level in the CD44


Neurological Manifestations As The Predictors Of Severity And Mortality In Hospitalized Individuals With Covid-19: A Multicenter Prospective Clinical Study, Man Amanat, Nima Rezaei, Mehrdad Roozbeh, Maziar Shojaei, Abbas Tafakhori, Anahita Zoghi, Ilad Alavi Darazam, Mona Salehi, Ehsan Karimialavijeh, Behnam Safarpour Lima, Amir Garakani, Alex R. Vaccaro, Mahtab Ramezani Mar 2021

Neurological Manifestations As The Predictors Of Severity And Mortality In Hospitalized Individuals With Covid-19: A Multicenter Prospective Clinical Study, Man Amanat, Nima Rezaei, Mehrdad Roozbeh, Maziar Shojaei, Abbas Tafakhori, Anahita Zoghi, Ilad Alavi Darazam, Mona Salehi, Ehsan Karimialavijeh, Behnam Safarpour Lima, Amir Garakani, Alex R. Vaccaro, Mahtab Ramezani

Department of Orthopaedic Surgery Faculty Papers

BACKGROUNDS: The reports of neurological symptoms are increasing in cases with coronavirus disease 2019 (COVID-19). This multi-center prospective study was conducted to determine the incidence of neurological manifestations in hospitalized cases with COVID-19 and assess these symptoms as the predictors of severity and death.

METHODS: Hospitalized males and females with COVID-19 who aged over 18 years were included in the study. They were examined by two neurologists at the time of admission. All survived cases were followed for 8 weeks after discharge and 16 weeks if their symptoms had no improvements.

RESULTS: We included 873 participants. Of eligible cases, 122 …


The Predictive Value Of Absolute Lymphocyte Counts On Tumor Progression And Pseudoprogression In Patients With Glioblastoma, Jing Xi, Bilal Hassan, Ruth G N Katumba, Karam Khaddour, Akshay Govindan, Jingqin Luo, Jiayi Huang, Jian L Campian Mar 2021

The Predictive Value Of Absolute Lymphocyte Counts On Tumor Progression And Pseudoprogression In Patients With Glioblastoma, Jing Xi, Bilal Hassan, Ruth G N Katumba, Karam Khaddour, Akshay Govindan, Jingqin Luo, Jiayi Huang, Jian L Campian

2020-Current year OA Pubs

BACKGROUND: Differentiating true glioblastoma multiforme (GBM) from pseudoprogression (PsP) remains a challenge with current standard magnetic resonance imaging (MRI). The objective of this study was to explore whether patients' absolute lymphocyte count (ALC) levels can be utilized to predict true tumor progression and PsP.

METHODS: Patients were considered eligible for the study if they had 1) GBM diagnosis, 2) a series of blood cell counts and clinical follow-ups, and 3) tumor progression documented by both MRI and pathology. Data analysis results include descriptive statistics, median (IQR) for continuous variables and count (%) for categorical variables, p values from Wilcoxon rank …


Obstetric Anesthesia Services In Israel Snapshot (Oasis) Study: A 72 Hour Cross-Sectional Observational Study Of Workforce Supply And Demand, Gal Schtrechman-Levi, Alexander Ioscovich, Jacob Hart, Jacob Bar, Ronit Calderon-Margalit, Eshel A Nir, Yehuda Ginosar Mar 2021

Obstetric Anesthesia Services In Israel Snapshot (Oasis) Study: A 72 Hour Cross-Sectional Observational Study Of Workforce Supply And Demand, Gal Schtrechman-Levi, Alexander Ioscovich, Jacob Hart, Jacob Bar, Ronit Calderon-Margalit, Eshel A Nir, Yehuda Ginosar

2020-Current year OA Pubs

BACKGROUND: We planned an observational study to assess obstetric anesthesia services nationwide. We aimed to assess the effect of the anesthesia workload/workforce ratio on quality and safety outcomes of obstetric anesthesia care.

METHODS: Observers prospectively collected data from labor units over 72 h (Wednesday, Thursday and Friday). Independent variables were workload (WL) and workforce (WF). WL was assessed by the Obstetric Anesthesia Activity Index (OAAI), which is the estimated time in a 24-h period spent on epidurals and all cesarean deliveries. Workforce (WF) was assessed by the number of anesthesiologists dedicated to the labor ward per week. Dependent variables were …


Severity Of Parkinsonism Associated With Environmental Manganese Exposure, Brad A Racette, Gill Nelson, Wendy W Dlamini, Pradeep Prathibha, Jay R Turner, Mwiza Ushe, Harvey Checkoway, Lianne Sheppard, Susan Searles Nielsen Mar 2021

Severity Of Parkinsonism Associated With Environmental Manganese Exposure, Brad A Racette, Gill Nelson, Wendy W Dlamini, Pradeep Prathibha, Jay R Turner, Mwiza Ushe, Harvey Checkoway, Lianne Sheppard, Susan Searles Nielsen

2020-Current year OA Pubs

BACKGROUND: Exposure to occupational manganese (Mn) is associated with neurotoxic brain injury, manifesting primarily as parkinsonism. The association between environmental Mn exposure and parkinsonism is unclear. To characterize the association between environmental Mn exposure and parkinsonism, we performed population-based sampling of residents older than 40 in Meyerton, South Africa (N = 621) in residential settlements adjacent to a large Mn smelter and in a comparable non-exposed settlement in Ethembalethu, South Africa (N = 95) in 2016-2020.

METHODS: A movement disorders specialist examined all participants using the Unified Parkinson Disease Rating Scale motor subsection part 3 (UPDRS3). Participants also completed an …


Whole-Genome Sequencing Of African Americans Implicates Differential Genetic Architecture In Inflammatory Bowel Disease, Hari K Somineni, Rodney D Newberry, Et Al. Mar 2021

Whole-Genome Sequencing Of African Americans Implicates Differential Genetic Architecture In Inflammatory Bowel Disease, Hari K Somineni, Rodney D Newberry, Et Al.

2020-Current year OA Pubs

Whether or not populations diverge with respect to the genetic contribution to risk of specific complex diseases is relevant to understanding the evolution of susceptibility and origins of health disparities. Here, we describe a large-scale whole-genome sequencing study of inflammatory bowel disease encompassing 1,774 affected individuals and 1,644 healthy control Americans with African ancestry (African Americans). Although no new loci for inflammatory bowel disease are discovered at genome-wide significance levels, we identify numerous instances of differential effect sizes in combination with divergent allele frequencies. For example, the major effect at PTGER4 fine maps to a single credible interval of 22 …


Association Of Blood Pressure Variability And Diuretics With Cardiovascular Events In Patients With Chronic Kidney Disease Stages 1-5, L Parker Gregg, S Susan Hedayati, Hui Yang, Peter N Van Buren, Subhash Banerjee, Sankar D Navaneethan, Salim S Virani, Wolfgang C Winkelmayer, Carlos A Alvarez Mar 2021

Association Of Blood Pressure Variability And Diuretics With Cardiovascular Events In Patients With Chronic Kidney Disease Stages 1-5, L Parker Gregg, S Susan Hedayati, Hui Yang, Peter N Van Buren, Subhash Banerjee, Sankar D Navaneethan, Salim S Virani, Wolfgang C Winkelmayer, Carlos A Alvarez

Faculty, Staff and Students Publications

Visit-to-visit blood pressure variability (BPV) is associated with cardiovascular events in the general population. Data are scarce in chronic kidney disease (CKD). We hypothesized that BPV would be associated with cardiovascular outcomes, death, and end-stage kidney disease (ESKD) and that diuretics would modify these associations in patients with CKD.

We studied U.S. Veterans with non-dialysis CKD stages 1-5 and hypertension on non-diuretic antihypertensive monotherapy. At the time of second antihypertensive agent prescription, we propensity-matched for exposure to a loop or thiazide diuretic vs. any other antihypertensive. BPV was defined as the coefficient of variation of systolic blood pressure over …


Corneal Nonmyelinating Schwann Cells Illuminated By Single-Cell Transcriptomics And Visualized By Protein Biomarkers., Paola Bargagna-Mohan, Gwendolyn Schultz, Bruce Rheaume, Ephraim F Trakhtenberg, Paul Robson, Sonali Pal-Ghosh, Mary Ann Stepp, Katherine S Given, Wendy B Macklin, Royce Mohan Mar 2021

Corneal Nonmyelinating Schwann Cells Illuminated By Single-Cell Transcriptomics And Visualized By Protein Biomarkers., Paola Bargagna-Mohan, Gwendolyn Schultz, Bruce Rheaume, Ephraim F Trakhtenberg, Paul Robson, Sonali Pal-Ghosh, Mary Ann Stepp, Katherine S Given, Wendy B Macklin, Royce Mohan

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.


Estimation And Comparison Of Current And Future Racial/Ethnic Representation In The Us Health Care Workforce., Edward Salsberg, Chelsea Richwine, Sara Westergaard, Maria Portela Martinez, Toyese Oyeyemi, Anushree Vichare, Candice P. Chen Mar 2021

Estimation And Comparison Of Current And Future Racial/Ethnic Representation In The Us Health Care Workforce., Edward Salsberg, Chelsea Richwine, Sara Westergaard, Maria Portela Martinez, Toyese Oyeyemi, Anushree Vichare, Candice P. Chen

Fitzhugh Mullan Institute for Health Workforce Equity

No abstract provided.


Limitations Of Conventional Magnetic Resonance Imaging As A Predictor Of Death Or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy In The Late Hypothermia Trial, Abbot R. Laptook, Seetha Shankaran, Patrick Barnes, Nancy Rollins, Barbara T. Do, Nehal A. Parikh, Shannon Hamrick, Susan R. Hintz, Jon E. Tyson, Edward F. Bell, Namasivayam Ambalavanan, Ronald N. Goldberg, Athina Pappas, Carolyn Huitema, Claudia Pedroza, Aasma S. Chaudhary, Angelita M. Hensman, Abhik Das, Myra Wyckoff, Amir Khan, Michelle C. Walsh, Kristi L. Watterberg, Roger Faix, William Truog, Ronnie Guillet, Gregory M. Sokol, Brenda B. Poindexter, Rosemary D. Higgins, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network Mar 2021

Limitations Of Conventional Magnetic Resonance Imaging As A Predictor Of Death Or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy In The Late Hypothermia Trial, Abbot R. Laptook, Seetha Shankaran, Patrick Barnes, Nancy Rollins, Barbara T. Do, Nehal A. Parikh, Shannon Hamrick, Susan R. Hintz, Jon E. Tyson, Edward F. Bell, Namasivayam Ambalavanan, Ronald N. Goldberg, Athina Pappas, Carolyn Huitema, Claudia Pedroza, Aasma S. Chaudhary, Angelita M. Hensman, Abhik Das, Myra Wyckoff, Amir Khan, Michelle C. Walsh, Kristi L. Watterberg, Roger Faix, William Truog, Ronnie Guillet, Gregory M. Sokol, Brenda B. Poindexter, Rosemary D. Higgins, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Neonatal Research Network

Pediatrics Research and Scholarship

OBJECTIVE: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours.

STUDY DESIGN: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to …


Fatigue And Its Association With Social Participation, Functioning, And Quality Of Life In Systemic Sclerosis, Susan L. Murphy, Anna L. Kratz, Daniel Whibley, Janet L. Poole, Dinesh Khanna Mar 2021

Fatigue And Its Association With Social Participation, Functioning, And Quality Of Life In Systemic Sclerosis, Susan L. Murphy, Anna L. Kratz, Daniel Whibley, Janet L. Poole, Dinesh Khanna

Pediatrics Research and Scholarship

OBJECTIVE: Fatigue is consistently ranked as one of the most problematic symptoms of systemic sclerosis (SSc), but the impact of fatigue on daily life is not well characterized. The purpose of this study was to examine the contribution of fatigue to deficits in social participation, functioning, and quality of life.

METHODS: Baseline data from a sample undertaking a clinical trial were utilized (n = 267). Fatigue, pain interference, depressive symptoms, physical function, and social participation were assessed by measures from the Patient-Reported Outcomes Measurement Information System. Hierarchical linear regressions were performed to determine the unique contribution of fatigue to social …


New Mexico's Covid-19 Experience, Nicole R. Jackson, Karen Zeigler, Mary Torrez, Yohsuke Makino, Natalie L. Adolphi, Sarah Lathrop, Lauren Decker, Lauren Dvorscak, Lori Proe, Ian D. Paul, Ross Zumwalt, Heather Jarrell Mar 2021

New Mexico's Covid-19 Experience, Nicole R. Jackson, Karen Zeigler, Mary Torrez, Yohsuke Makino, Natalie L. Adolphi, Sarah Lathrop, Lauren Decker, Lauren Dvorscak, Lori Proe, Ian D. Paul, Ross Zumwalt, Heather Jarrell

Pathology Research and Scholarship

The 2019 novel coronavirus disease (COVID-19) has spread worldwide, infiltrating, infecting, and devastating communities in all locations of varying demographics. An overwhelming majority of published literature on the pathologic findings associated with COVID-19 is either from living clinical cohorts or from autopsy findings of those who died in a medical care setting, which can confound pure disease pathology. A relatively low initial infection rate paired with a high biosafety level enabled the New Mexico Office of the Medical Investigator to conduct full autopsy examinations on suspected COVID-19-related deaths. Full autopsy examination on the first 20 severe acute respiratory syndrome coronavirus …


Surveillance Systems For Monitoring Cervical Cancer Elimination Efforts: Focus On Hpv Infection, Cervical Dysplasia, Cervical Screening And Treatment., Julia M L Brotherton, Cosette Wheeler, Gary M. Clifford, Miriam Elfström, Marion Saville, John Kaldor, Dorothy A. Machalek Mar 2021

Surveillance Systems For Monitoring Cervical Cancer Elimination Efforts: Focus On Hpv Infection, Cervical Dysplasia, Cervical Screening And Treatment., Julia M L Brotherton, Cosette Wheeler, Gary M. Clifford, Miriam Elfström, Marion Saville, John Kaldor, Dorothy A. Machalek

Pathology Research and Scholarship

In order to achieve the global elimination of cervical cancer as a public health problem, close surveillance of progress in public health and clinical activities and outcomes across the three pillars of vaccination, screening and treatment will be required. Surveillance should ideally occur within an integrated system that is planned, funded, and regularly evaluated to ensure it is providing timely, accurate and relevant feedback for action. In this paper, we conceptualise the main public health surveillance objectives as process and outcome measures in each of the three pillars. Process measures include coverage/participation measures for vaccination, screening and treatment alongside the …


A Brazilian National Preparedness Survey Of Anesthesiologists During The Coronavirus Pandemic, Vinícius Caldeira Quintão, Claudia Marquez Simões, Gibran Elias Harcha Munoz, Paul Barach, Maria José Carvalho Carmona, Brazilian Network For Research On Complications In Anesthesia Branca Mar 2021

A Brazilian National Preparedness Survey Of Anesthesiologists During The Coronavirus Pandemic, Vinícius Caldeira Quintão, Claudia Marquez Simões, Gibran Elias Harcha Munoz, Paul Barach, Maria José Carvalho Carmona, Brazilian Network For Research On Complications In Anesthesia Branca

College of Population Health Faculty Papers

No abstract provided.


Pancreatic Cancer Is Marked By Complement-High Blood Monocytes And Tumor-Associated Macrophages, Samantha B. Kemp, Nina G. Steele, Eileen S. Carpenter, Katelyn L. Donahue, Grace G. Bushnell, Aaron H. Morris, Stephanie The, Sophia M. Orbach, Veerin R. Sirihorachai, Zeribe C. Nwosu, Carlos Espinoza, Fatima Lima, Kristee Brown, Alexander A. Girgis, Valerie Gunchick, Yaqing Zhang, Costas A. Lyssiotis, Timothy L. Frankel, Filip Bednar, Arvind Rao, Vaibhav Sahai, Lonnie D. Shea, Howard C. Crawford, Marina Pasca Di Magliano Mar 2021

Pancreatic Cancer Is Marked By Complement-High Blood Monocytes And Tumor-Associated Macrophages, Samantha B. Kemp, Nina G. Steele, Eileen S. Carpenter, Katelyn L. Donahue, Grace G. Bushnell, Aaron H. Morris, Stephanie The, Sophia M. Orbach, Veerin R. Sirihorachai, Zeribe C. Nwosu, Carlos Espinoza, Fatima Lima, Kristee Brown, Alexander A. Girgis, Valerie Gunchick, Yaqing Zhang, Costas A. Lyssiotis, Timothy L. Frankel, Filip Bednar, Arvind Rao, Vaibhav Sahai, Lonnie D. Shea, Howard C. Crawford, Marina Pasca Di Magliano

Research Administration Articles

Pancreatic ductal adenocarcinoma (PDA) is accompanied by reprogramming of the local microenvironment, but changes at distal sites are poorly understood. We implanted biomaterial scaffolds, which act as an artificial premetastatic niche, into immunocompetent tumor-bearing and control mice, and identified a unique tumor-specific gene expression signature that includes high expression of C1qa, C1qb, Trem2, and Chil3 Single-cell RNA sequencing mapped these genes to two distinct macrophage populations in the scaffolds, one marked by elevated C1qa, C1qb, and Trem2, the other with high Chil3, Ly6c2 and Plac8 In mice, expression of these genes in the corresponding populations was elevated in tumor-associated macrophages …


Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer Mar 2021

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …


Prematurity Blunts The Insulin- And Amino Acid-Induced Stimulation Of Translation Initiation And Protein Synthesis In Skeletal Muscle Of Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Barbara Stoll, Candace C Style, Mariatu A Verla, Oluyinka O Olutoye, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis Mar 2021

Prematurity Blunts The Insulin- And Amino Acid-Induced Stimulation Of Translation Initiation And Protein Synthesis In Skeletal Muscle Of Neonatal Pigs, Marko Rudar, Jane K Naberhuis, Agus Suryawan, Hanh V Nguyen, Barbara Stoll, Candace C Style, Mariatu A Verla, Oluyinka O Olutoye, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Children’s Nutrition Research Center Staff Publications

Extrauterine growth restriction in premature infants is largely attributed to reduced lean mass accretion and is associated with long-term morbidities. Previously, we demonstrated that prematurity blunts the feeding-induced stimulation of translation initiation signaling and protein synthesis in skeletal muscle of neonatal pigs. The objective of the current study was to determine whether the blunted feeding response is mediated by reduced responsiveness to insulin, amino acids, or both. Pigs delivered by cesarean section preterm (PT; 103 days,


Perfluorooctanoic Acid (Pfoa) Or Perfluorooctane Sulfonate (Pfos) And Dna Methylation In Newborn Dried Blood Spots In The Upstate Kids Cohort, Sonia L Robinson, Xuehuo Zeng, Weihua Guan, Rajeshwari Sundaram, Pauline Mendola, Diane L Putnick, Robert A Waterland, Chathura J Gunasekara, Kurunthachalam Kannan, Chongjing Gao, Erin M Bell, Edwina H Yeung Mar 2021

Perfluorooctanoic Acid (Pfoa) Or Perfluorooctane Sulfonate (Pfos) And Dna Methylation In Newborn Dried Blood Spots In The Upstate Kids Cohort, Sonia L Robinson, Xuehuo Zeng, Weihua Guan, Rajeshwari Sundaram, Pauline Mendola, Diane L Putnick, Robert A Waterland, Chathura J Gunasekara, Kurunthachalam Kannan, Chongjing Gao, Erin M Bell, Edwina H Yeung

Children’s Nutrition Research Center Staff Publications

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are persistent organic pollutants which may alter prenatal development, potentially through epigenetic modifications. Prior studies examining PFOS/PFOA and DNA methylation have relatively few subjects (n < 200) and inconsistent results. We examined relations of PFOA/PFOS with DNA methylation among 597 neonates in the Upstate KIDS cohort study. PFOA/PFOS were quantified in newborn dried blood spots (DBS) using high-performance liquid chromatography/tandem mass spectrometry. DNA methylation was measured using the Infinium MethylationEPIC BeadChip with DNA extracted from DBS. Robust linear regression was used to examine the associations of PFOA/PFOS with DNA methylation at individual CpG sites. Covariates included sample plate, estimated cell type, epigenetically derived ancestry, infant sex and plurality, indicators of maternal socioeconomic status, and prior pregnancy loss. In supplemental analysis, we restricted the analysis to 2242 CpG sites previously identified as Correlated Regions of Systemic Interindividual Variation (CoRSIVs) which include metastable epialleles. At FDR90th percentile was related to DNA methylation at cg15557840, near SCRT2, SRXN1; PFOS>90th percentile was related to 2 CpG sites in a sex-specific manner (cg19039925 in GVIN1 in boys and cg05754408 in ZNF26 in girls). When analysis was restricted to CoRSIVs, log-scaled, continuous PFOS concentration was related to DNA methylation at cg03278866 within PTBP1. In conclusion, there was limited evidence of an association between high concentrations of PFOA/PFOS and DNA methylation in newborn DBS in the Upstate KIDS cohort. These …


The Association Between Overnight Fasting And Body Mass Index In Older Adults: The Interaction Between Duration And Timing, Qian Xiao, Cici Bauer, Tracy Layne, Mary Playdon Mar 2021

The Association Between Overnight Fasting And Body Mass Index In Older Adults: The Interaction Between Duration And Timing, Qian Xiao, Cici Bauer, Tracy Layne, Mary Playdon

Faculty, Staff and Student Publications

BACKGROUND: Circadian rhythms play an important role in the regulation of eating and fasting, and mistimed dietary intakes may be detrimental to metabolic health. Extended overnight fasting has been proposed as a strategy to better align the eating-fasting cycle with the internal circadian clock, and both observational and experimental studies have linked longer overnight fasting with lower body weight. However, it remains unclear if the timing of overnight fasting modifies the relationship between fasting duration and weight outcomes.

METHODS: The current study included 495 men and 499 women age 50-74 years. Dietary intake over 12 months was assessed by 24-h …


Increased Functional Coupling Between Vta And Hippocampus During Rest In First-Episode Psychosis, David F Gregory, Jane M Rothrock, Maria Jalbrzikowski, William Foran, David F Montez, Beatriz Luna, Vishnu P Murty Mar 2021

Increased Functional Coupling Between Vta And Hippocampus During Rest In First-Episode Psychosis, David F Gregory, Jane M Rothrock, Maria Jalbrzikowski, William Foran, David F Montez, Beatriz Luna, Vishnu P Murty

Open Access Publications

Animal models suggest that interactions between the hippocampus and ventral tegmental area (VTA) underlie the onset and etiology of psychosis. While a large body of research has separately characterized alterations in hippocampal and VTA function in psychosis, alterations across the VTA and hippocampus have not been characterized in first-episode psychosis (FEP). As the phase of psychosis most proximal to conversion, studies specifically focused on FEP are valuable to psychosis research. Here, we characterize alterations in VTA-hippocampal interactions across male and female human participants experiencing their first episode of psychosis using resting state functional magnetic resonance imaging (rsfMRI). In comparison to …


Correlation Of Pd-L1 Expression, Clinicopathologic And Molecular Characteristics In An Array Of Solid Tumors: A Large-Scale Real World Study, Kanika Arora, Harshita Mehrotra, Kasturi Saikia, Rand Abou Shaar, Mohamed Alhamar, Dhananjay A. Chitale Mar 2021

Correlation Of Pd-L1 Expression, Clinicopathologic And Molecular Characteristics In An Array Of Solid Tumors: A Large-Scale Real World Study, Kanika Arora, Harshita Mehrotra, Kasturi Saikia, Rand Abou Shaar, Mohamed Alhamar, Dhananjay A. Chitale

Pathology Meeting Abstracts

Background: Programmed death ligand-1 (PD-L1) is a predictive marker of anti-programmed death protein 1 (PD- 1)/PD-L1 therapies for solid tumors. Limited literature exists correlating PD-L1 expression, clinicopathological & molecular profiles. We aimed to 1) correlate PD-L1 immunohistochemistry (IHC) results with these profile across multiple solid tumors & 2) assess clinical outcomes (overall survival (OS) & disease-free survival (DFS)) of PD-L1 status with / without anti-PD-L1 immunotherapy (IT).

Design: All cases tested for PD-L1 IHC over 2 years (Aug 2019-Sep 2020) were retrieved for this study. Clinicopathological variables recorded included age, race, tumor type, type of PD-L1 clone, PD-L1 status (Tumor …


Hepatotoxicity Following Administration Of Onasemnogene Abeparvovec (Avxs-101) For The Treatment Of Spinal Muscular Atrophy, Deepa Chand, Franziska Mohr, Hugh Mcmillan, Francis Fonyuy Tukov, Kyle Montgomery, Aaron Kleyn, Rui Sun, Sitra Tauscher-Wisniewski, Petra Kaufmann, Gerd Kullak-Ublick Mar 2021

Hepatotoxicity Following Administration Of Onasemnogene Abeparvovec (Avxs-101) For The Treatment Of Spinal Muscular Atrophy, Deepa Chand, Franziska Mohr, Hugh Mcmillan, Francis Fonyuy Tukov, Kyle Montgomery, Aaron Kleyn, Rui Sun, Sitra Tauscher-Wisniewski, Petra Kaufmann, Gerd Kullak-Ublick

2020-Current year OA Pubs

BACKGROUND & AIMS: Spinal muscular atrophy (SMA) is an autosomal recessive, childhood-onset motor neuron disease. Onasemnogene abeparvovec (OA) is a gene therapy designed to address SMA's root cause. In pivotal mouse toxicology studies, the liver was identified as a major site of OA toxicity. Clinical data reflect elevations in serum aminotransferase concentrations, with some reports of serious acute liver injury. Prophylactic prednisolone mitigates these effects. Herein, we aim to provide pragmatic, supportive guidance for identification, management, and risk mitigation of potential drug-induced liver injury.

METHODS: Data from 325 patients with SMA who had received OA through 31 December 2019, in …


A Biallelic Pathogenic Variant In The Ogdh Gene Results In A Neurological Disorder With Features Of A Mitochondrial Disease, Zheng Yie Yap, Klaudia Strucinska, Satoshi Matsuzaki, Sukyeong Lee, Yue Si, Kenneth Humphries, Mark A Tarnopolsky, Wan Hee Yoon Mar 2021

A Biallelic Pathogenic Variant In The Ogdh Gene Results In A Neurological Disorder With Features Of A Mitochondrial Disease, Zheng Yie Yap, Klaudia Strucinska, Satoshi Matsuzaki, Sukyeong Lee, Yue Si, Kenneth Humphries, Mark A Tarnopolsky, Wan Hee Yoon

Faculty, Staff and Students Publications

2-Oxoglutarate dehydrogenase (OGDH) is a rate-limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α-Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in …


Tbx5-Encoded T-Box Transcription Factor 5 Variant T223m Is Associated With Long Qt Syndrome And Pediatric Sudden Cardiac Death, Alexandra M Markunas, Perathu K R Manivannan, Jordan E Ezekian, Agnim Agarwal, William Eisner, Katherina Alsina, Hugh D Allen, Gregory A Wray, Jeffrey J Kim, Xander H T Wehrens, Andrew P Landstrom Mar 2021

Tbx5-Encoded T-Box Transcription Factor 5 Variant T223m Is Associated With Long Qt Syndrome And Pediatric Sudden Cardiac Death, Alexandra M Markunas, Perathu K R Manivannan, Jordan E Ezekian, Agnim Agarwal, William Eisner, Katherina Alsina, Hugh D Allen, Gregory A Wray, Jeffrey J Kim, Xander H T Wehrens, Andrew P Landstrom

Faculty, Staff and Students Publications

Long QT syndrome (LQTS) is a genetic disease resulting in a prolonged QT interval on a resting electrocardiogram, predisposing affected individuals to polymorphic ventricular tachycardia and sudden death. Although a number of genes have been implicated in this disease, nearly one in four individuals exhibiting the LQTS phenotype are genotype-negative. Whole-exome sequencing identified a missense T223M variant in TBX5 that cosegregates with prolonged QT interval in a family with otherwise genotype-negative LQTS and sudden death. The TBX5-T223M variant was absent among large ostensibly healthy populations (gnomAD) and predicted to be pathogenic by in silico modeling based on Panther, PolyPhen-2, Provean, …


Pegylated Arginine Deiminase Depletes Plasma Arginine But Maintains Tissue Arginine Availability In Young Pigs, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Trung C Nguyen, Juan C Marini Mar 2021

Pegylated Arginine Deiminase Depletes Plasma Arginine But Maintains Tissue Arginine Availability In Young Pigs, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Trung C Nguyen, Juan C Marini

Faculty, Staff and Students Publications

Pegylated arginine deiminase (ADI-PEG20) results in the depletion of arginine with the production of isomolar amounts of citrulline. This citrulline has the potential to be utilized by the citrulline recycling pathway regenerating arginine and sustaining tissue arginine availability. The goal of this research was to test the hypothesis that ADI-PEG20 depletes circulating arginine in pigs but maintains tissue arginine concentration and function, and to characterize the kinetics of citrulline and arginine. Two multitracer approaches (bolus dose and primed-continuous infusion) were used to investigate the metabolism of arginine and citrulline in Control (


Deficiency Of Stat1 In Cd11c+ Cells Alters Adipose Tissue Inflammation And Improves Metabolic Dysfunctions In Mice Fed A High-Fat Diet, Antu Antony, Zeqin Lian, Xiaoyuan Dai Perrard, Jerry Perrard, Hua Liu, Aaron R Cox, Pradip Saha, Lothar Hennighausen, Sean M Hartig, Christie M Ballantyne, Huaizhu Wu Mar 2021

Deficiency Of Stat1 In Cd11c+ Cells Alters Adipose Tissue Inflammation And Improves Metabolic Dysfunctions In Mice Fed A High-Fat Diet, Antu Antony, Zeqin Lian, Xiaoyuan Dai Perrard, Jerry Perrard, Hua Liu, Aaron R Cox, Pradip Saha, Lothar Hennighausen, Sean M Hartig, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

CD11c+ macrophages/dendritic cells (MDCs) are increased and display the classically activated M1-like phenotype in obese adipose tissue (AT) and may contribute to AT inflammation and insulin resistance. Stat1 is a key transcription factor for MDC polarization into the M1-like phenotype. Here, we examined the role of Stat1 in obesity-induced AT MDC polarization and inflammation and insulin resistance using mice with specific knockout of Stat1 in MDCs (cKO). Stat1 was upregulated and phosphorylated, indicating activation, early and persistently in AT and AT MDCs of wild-type mice fed a high-fat diet (HFD). Compared with littermate controls, cKO mice fed an HFD (16 …


Effect Of Aspirin On Cancer Incidence And Mortality In Older Adults, John J Mcneil, Yin Cao, Et Al. Mar 2021

Effect Of Aspirin On Cancer Incidence And Mortality In Older Adults, John J Mcneil, Yin Cao, Et Al.

2020-Current year OA Pubs

BACKGROUND: ASPirin in Reducing Events in the Elderly, a randomized, double-blind, placebo-controlled trial of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast, prior randomized controlled trials, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality.

METHODS: 19 114 Australian and US community-dwelling participants aged 70 years and older (US minorities 65 years and older) without cardiovascular disease, dementia, or physical disability were randomly assigned and followed for a median of 4.7 years. Fatal and nonfatal …


The Structure And Diversity Of Strain-Level Variation In Vaginal Bacteria, Brett A Tortelli, Amanda L Lewis, Justin C Fay Mar 2021

The Structure And Diversity Of Strain-Level Variation In Vaginal Bacteria, Brett A Tortelli, Amanda L Lewis, Justin C Fay

2020-Current year OA Pubs

The vaginal microbiome plays an important role in human health and species of vaginal bacteria have been associated with reproductive disease. Strain-level variation is also thought to be important, but the diversity, structure and evolutionary history of vaginal strains is not as well characterized. We developed and validated an approach to measure strain variation from metagenomic data based on SNPs within the core genomes for six species of vaginal bacteria:


Covid-19 In Solid Organ Transplantation: Disease Severity And Clinical Update., Akanksha Arya, Michael Li, Nana Aburjania, Pooja Singh, Tricia. Royer, Sean Moss, Katherine A. Belden Feb 2021

Covid-19 In Solid Organ Transplantation: Disease Severity And Clinical Update., Akanksha Arya, Michael Li, Nana Aburjania, Pooja Singh, Tricia. Royer, Sean Moss, Katherine A. Belden

Department of Medicine Faculty Papers

BACKGROUND: Solid organ transplant (SOT) recipients are a complex, immunocompromised population in whom greater coronavirus disease 2019 (COVID-19) mortality has been reported compared with the general population.

METHODS: We examined a retrospective cohort of 58 SOT recipients with first-wave COVID-19, comparing patients with severe and nonsevere illness. Additionally, SOT recipients are compared with general patients with first-wave COVID-19.

RESULTS: Organs transplanted included 38 kidneys, 8 livers, 5 hearts, and 3 pancreases. Average SOT recipient age was 57.4 years; 62% were male; 46.6% were African American 36.2% were white. Comorbidities included hypertension (86%), chronic kidney disease (86%), diabetes mellitus (50%), coronary …


Drug Susceptibility Patterns Of Mycobacterium Tuberculosis From Adults With Multidrug-Resistant Tuberculosis And Implications For A Household Contact Preventive Therapy Trial, Anne-Marie Demers, Soyeon Kim, Sara Mccallum, Kathleen Eisenach, Michael Hughes, Linda Naini, Alberto Mendoza-Ticona, Neeta Pradhan, Kim Narunsky, Selvamuthu Poongulali, Sharlaa Badal-Faesen, Caryn Upton, Elizabeth Smith, N Sarita Shah, Gavin Churchyard, Amita Gupta, Anneke Hesseling, Susan Swindells, Actg A5300/Impaact I2003 Phoenix Feasibility Study Team Feb 2021

Drug Susceptibility Patterns Of Mycobacterium Tuberculosis From Adults With Multidrug-Resistant Tuberculosis And Implications For A Household Contact Preventive Therapy Trial, Anne-Marie Demers, Soyeon Kim, Sara Mccallum, Kathleen Eisenach, Michael Hughes, Linda Naini, Alberto Mendoza-Ticona, Neeta Pradhan, Kim Narunsky, Selvamuthu Poongulali, Sharlaa Badal-Faesen, Caryn Upton, Elizabeth Smith, N Sarita Shah, Gavin Churchyard, Amita Gupta, Anneke Hesseling, Susan Swindells, Actg A5300/Impaact I2003 Phoenix Feasibility Study Team

Journal Articles: Internal Medicine

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs).

METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations …