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Alcohol And Its Long-Term Effects On Hearing Loss: A Systematic Review, Talia Sowalsky Jun 2021

Alcohol And Its Long-Term Effects On Hearing Loss: A Systematic Review, Talia Sowalsky

Dissertations, Theses, and Capstone Projects

Objective: To review the literature on potential permanent effects of long-term alcohol consumption on hearing status in adults 40 years of age and older.

Study Design: Systematic review of prospective and retrospective studies; meta-analysis of case-controlled studies.

Methods: One researcher independently reviewed MEDLINE (January 1, 2000-May 1, 2019), CINAHL (January 1, 2000-May 1, 2019), PubMed (January 1, 2000-May 1, 2019), and Web of Science (January 1, 2000-May 1, 2019). A manual reference search was additionally conducted. Randomized controlled trials, prospective cohort studies, consecutive/non-consecutive case series, and retrospective reviews in which a clear definition of hearing loss was stated were included …


Defining Vdr Expression In The Brain Using A Novel Vdrcre Mouse, Hailan Liu, Yang He, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Yong Xu, Stephanie Sisley Jun 2021

Defining Vdr Expression In The Brain Using A Novel Vdrcre Mouse, Hailan Liu, Yang He, Jessie Beck, Silvania Da Silva Teixeira, Keisha Harrison, Yong Xu, Stephanie Sisley

Children’s Nutrition Research Center Staff Publications

Vitamin D action has been linked to several diseases regulated by the brain including obesity, diabetes, autism, and Parkinson’s. However, the location of the vitamin D receptor (VDR) in the brain is not clear due to conflicting reports. We found that two antibodies previously published as specific in peripheral tissues are not specific in the brain. We thus created a new knockin mouse with cre recombinase expression under the control of the endogenous VDR promoter (VDRCre). We demonstrated that the cre activity in the VDRCre mouse brain (as reported by a cre-dependent tdTomato expression) is highly overlapping with endogenous VDR …


Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao Jun 2021

Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao

Publications

Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) …


Ube2i Deletion In Adipocytes Causes Lipoatrophy In Mice, Aaron R Cox, Natasha Chernis, Kang Ho Kim, Peter M Masschelin, Pradip K Saha, Shawn M Briley, Robert Sharp, Xin Li, Jessica B Felix, Zheng Sun, David D Moore, Stephanie A Pangas, Sean M Hartig Jun 2021

Ube2i Deletion In Adipocytes Causes Lipoatrophy In Mice, Aaron R Cox, Natasha Chernis, Kang Ho Kim, Peter M Masschelin, Pradip K Saha, Shawn M Briley, Robert Sharp, Xin Li, Jessica B Felix, Zheng Sun, David D Moore, Stephanie A Pangas, Sean M Hartig

Faculty, Staff and Students Publications

OBJECTIVE: White adipose tissue (WAT) expansion regulates energy balance and overall metabolic homeostasis. The absence or loss of WAT occurring through lipodystrophy and lipoatrophy contributes to the development of hepatic steatosis and insulin resistance. We previously demonstrated that sole small ubiquitin-like modifier (SUMO) E2-conjugating enzyme Ube2i represses human adipocyte differentiation. The role of Ube2i during WAT development remains unknown.

METHODS: To determine how Ube2i impacts body composition and energy balance, we generated adipocyte-specific Ube2i knockout mice (Ube2i

RESULTS: Surprisingly, Ube2i

CONCLUSIONS: Our results demonstrate that Ube2i expression in mature adipocytes allows WAT expansion during postnatal growth. Deletion of Ube2i in …


Cell Lineage Tracing Links Erα Loss In Erbb2-Positive Breast Cancers To The Arising Of A Highly Aggressive Breast Cancer Subtype, Yunfeng Ding, Yonghong Liu, Dong-Kee Lee, Zhangwei Tong, Xiaobin Yu, Yi Li, Yong Xu, Rainer B Lanz, Bert W O'Malley, Jianming Xu May 2021

Cell Lineage Tracing Links Erα Loss In Erbb2-Positive Breast Cancers To The Arising Of A Highly Aggressive Breast Cancer Subtype, Yunfeng Ding, Yonghong Liu, Dong-Kee Lee, Zhangwei Tong, Xiaobin Yu, Yi Li, Yong Xu, Rainer B Lanz, Bert W O'Malley, Jianming Xu

Children’s Nutrition Research Center Staff Publications

HER2-positive (HER2+) breast cancers (BrCs) contain approximately equal numbers of ERα+HER2+ and ERα−HER2+ cases. An enduring obstacle is the unclear cell lineage-related characteristics of these BrCs. Although ERα+HER2+ BrCs could lose ERα to become ERα−HER2+ BrCs, direct evidence is missing. To investigate ERα dependencies and their implications during BrC growth and metastasis, we generated ERαCreRFP-T mice that produce an RFP-marked ERα+ mammary gland epithelial cell (MGEC) lineage. RCAS virus-mediated expression of Erbb2, a rodent Her2 homolog, first produced comparable numbers of ERα+RFP+Erbb2+ and ERα−RFP−Erbb2+ MGECs. Early hyperplasia developed mostly from ERα+RFP+Erbb2+ cells and ERα−RFP−Erbb2+ cells in these lesions were rare. …


Cancer-Associated Mutations Reveal A Novel Role For Epcam As An Inhibitor Of Cathepsin-L And Tumor Cell Invasion, Narendra V Sankpal, Taylor C Brown, Timothy P Fleming, John M Herndon, Anusha A Amaravati, Allison N Loynd, William E Gillanders May 2021

Cancer-Associated Mutations Reveal A Novel Role For Epcam As An Inhibitor Of Cathepsin-L And Tumor Cell Invasion, Narendra V Sankpal, Taylor C Brown, Timothy P Fleming, John M Herndon, Anusha A Amaravati, Allison N Loynd, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors.

METHODS: The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of …


Consumption Of High-Fructose Corn Syrup Compared With Sucrose Promotes Adiposity And Increased Triglyceridemia But Comparable Nafld Severity In Juvenile Iberian Pigs, Magdalena Maj, Brooke Harbottle, Payton A Thomas, Gabriella V Hernandez, Victoria A Smith, Mark S Edwards, Rob K Fanter, Hunter S Glanz, Chad Immoos, Douglas G Burrin, Tasha M Santiago-Rodriguez, Michael R La Frano, Rodrigo Manjarín May 2021

Consumption Of High-Fructose Corn Syrup Compared With Sucrose Promotes Adiposity And Increased Triglyceridemia But Comparable Nafld Severity In Juvenile Iberian Pigs, Magdalena Maj, Brooke Harbottle, Payton A Thomas, Gabriella V Hernandez, Victoria A Smith, Mark S Edwards, Rob K Fanter, Hunter S Glanz, Chad Immoos, Douglas G Burrin, Tasha M Santiago-Rodriguez, Michael R La Frano, Rodrigo Manjarín

Children’s Nutrition Research Center Staff Publications

Background: Fructose consumption has been linked to nonalcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) compared with sucrose in pediatric NAFLD has not been investigated.

Objectives: We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, SCFA production, and microbial diversity.

Methods: Iberian pigs, 53-d-old and pair-housed in pens balanced for weight and sex, were randomly assigned to receive a mash diet top-dressed with increasing amounts of sucrose (SUC; n = …


The Impact Of Erythropoietin On Short- And Long-Term Kidney-Related Outcomes In Neonates Of Extremely Low Gestational Age. Results Of A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial, David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Patrick Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani, Jean Lowe, Penut Trial Consortium May 2021

The Impact Of Erythropoietin On Short- And Long-Term Kidney-Related Outcomes In Neonates Of Extremely Low Gestational Age. Results Of A Multicenter, Double-Blind, Placebo-Controlled Randomized Clinical Trial, David J. Askenazi, Patrick J. Heagerty, Robert H. Schmicker, Patrick Brophy, Sandra E. Juul, Stuart L. Goldstein, Sangeeta Hingorani, Jean Lowe, Penut Trial Consortium

Pediatrics Research and Scholarship

OBJECTIVE: To evaluate whether extremely low gestational age neonates (ELGANs) randomized to erythropoietin have better or worse kidney-related outcomes during hospitalization and at 22-26 months of corrected gestational age (cGA) compared with those randomized to placebo.

STUDY DESIGN: We performed an ancillary study to a multicenter double-blind, placebo-controlled randomized clinical trial of erythropoietin in ELGANs.

RESULTS: The prevalence of severe (stage 2 or 3) acute kidney injury (AKI) was 18.2%. We did not find a statistically significant difference between those randomized to erythropoietin vs placebo for in-hospital primary (severe AKI) or secondary outcomes (any AKI and serum creatinine/cystatin C values …


Effectiveness Of Diet/Exercise In Prevention Of Gestational Diabetes Mellitus And Associated Cesarean Section Delivery, Jonathyn Andrew Marx May 2021

Effectiveness Of Diet/Exercise In Prevention Of Gestational Diabetes Mellitus And Associated Cesarean Section Delivery, Jonathyn Andrew Marx

Physician Assistant Scholarly Project Papers

Gestational diabetes mellitus (GDM) is becoming a more common diagnosis during pregnancy. GDM is defined as glucose intolerance diagnosed during pregnancy. Women diagnosed with GDM during pregnancy are at an increased risk for emergent or planned cesarean section delivery and the development of overt diabetes mellitus post pregnancy. Complications related to GDM include eclampsia, macrosomia, shoulder dystocia, stillbirth, and cesarean section delivery. Initial treatment consists of diet and exercise and if glucose can not be controlled then pharmacotherapy is introduced. A literature review was performed utilizing scientific databases, mesh terms, and keywords to gather statistically relevant research to analyze the …


Umbilical Cord Milking Vs Delayed Cord Clamping And Associations With In-Hospital Outcomes Among Extremely Premature Infants, Neha Kumbhat, Barry Eggleston, Alexis S. Davis, Sara B. Demauro, Krisa P. Van Meurs, Elizabeth E. Foglia, Satyan Lakshminrusimha, Michele C. Walsh, Kristi L. Watterberg, Myra H. Wyckoff, Abhik Das, Sara C. Handley, Generic Database Subcommittee Of The Nichd Neonatal Research Network May 2021

Umbilical Cord Milking Vs Delayed Cord Clamping And Associations With In-Hospital Outcomes Among Extremely Premature Infants, Neha Kumbhat, Barry Eggleston, Alexis S. Davis, Sara B. Demauro, Krisa P. Van Meurs, Elizabeth E. Foglia, Satyan Lakshminrusimha, Michele C. Walsh, Kristi L. Watterberg, Myra H. Wyckoff, Abhik Das, Sara C. Handley, Generic Database Subcommittee Of The Nichd Neonatal Research Network

Pediatrics Research and Scholarship

OBJECTIVE: To compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infantsgestation.

STUDY DESIGN: Multicenter retrospective study of infants born(grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-24

RESULTS: Among 1834 infants, 23.6% were exposed to umbilical cord milking …


Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne May 2021

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne

Faculty, Staff and Students Publications

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels …


Gardnerella Vaginalis Promotes Group B Streptococcus Vaginal Colonization, Enabling Ascending Uteroplacental Infection In Pregnant Mice, Nicole M Gilbert, Lynne R Foster, Bin Cao, Yin Yin, Indira U Mysorekar, Amanda L Lewis May 2021

Gardnerella Vaginalis Promotes Group B Streptococcus Vaginal Colonization, Enabling Ascending Uteroplacental Infection In Pregnant Mice, Nicole M Gilbert, Lynne R Foster, Bin Cao, Yin Yin, Indira U Mysorekar, Amanda L Lewis

2020-Current year OA Pubs

BACKGROUND: Group B Streptococcus is a common vaginal bacterium and the leading cause of invasive fetoplacental infections. Group B Streptococcus in the vagina can invade through the cervix to cause ascending uteroplacental infections or can be transmitted to the neonate during vaginal delivery. Some studies have found that women with a "dysbiotic" polymicrobial or Lactobacillus-depleted vaginal microbiota are more likely to harbor group B Streptococcus. Gardnerella vaginalis is often the most abundant bacteria in the vaginas of women with dysbiosis, while being detected at lower levels in most other women, and has been linked with several adverse pregnancy outcomes. Mouse …


T-Cell Activation Profiles Distinguish Hemophagocytic Lymphohistiocytosis And Early Sepsis, Vandana Chaturvedi, Rebecca A Marsh, Adi Zoref-Lorenz, Erika Owsley, Vijaya Chaturvedi, Trung C Nguyen, Jordana R Goldman, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Jeng, Ahmed Naqvi, Carl E Allen, Hector R Wong, Michael B Jordan Apr 2021

T-Cell Activation Profiles Distinguish Hemophagocytic Lymphohistiocytosis And Early Sepsis, Vandana Chaturvedi, Rebecca A Marsh, Adi Zoref-Lorenz, Erika Owsley, Vijaya Chaturvedi, Trung C Nguyen, Jordana R Goldman, Michael M Henry, Jay N Greenberg, Stephan Ladisch, Michelle L Hermiston, Michael Jeng, Ahmed Naqvi, Carl E Allen, Hector R Wong, Michael B Jordan

Faculty, Staff and Students Publications

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disorder of immune hyperactivation that has been described as a cytokine storm. Sepsis due to known or suspected infection has also been viewed as a cytokine storm. Although clinical similarities between these syndromes suggest similar immunopathology and may create diagnostic uncertainty, distinguishing them is critical as treatments are widely divergent. We examined T-cell profiles from children with either HLH or sepsis and found that HLH is characterized by acute T-cell activation, in clear contrast to sepsis. Activated T cells in patients with HLH were characterized as CD38high/HLA-DR+ effector cells, with activation of CD8+ T …


Oncolytic Hsv-1 G207 Immunovirotherapy For Pediatric High-Grade Gliomas, Gregory K Friedman, Mohamed S Abdelbaki, Et Al Apr 2021

Oncolytic Hsv-1 G207 Immunovirotherapy For Pediatric High-Grade Gliomas, Gregory K Friedman, Mohamed S Abdelbaki, Et Al

Open Access Publications

BACKGROUND: Outcomes in children and adolescents with recurrent or progressive high-grade glioma are poor, with a historical median overall survival of 5.6 months. Pediatric high-grade gliomas are largely immunologically silent or "cold," with few tumor-infiltrating lymphocytes. Preclinically, pediatric brain tumors are highly sensitive to oncolytic virotherapy with genetically engineered herpes simplex virus type 1 (HSV-1) G207, which lacks genes essential for replication in normal brain tissue.

METHODS: We conducted a phase 1 trial of G207, which used a 3+3 design with four dose cohorts of children and adolescents with biopsy-confirmed recurrent or progressive supratentorial brain tumors. Patients underwent stereotactic placement …


A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al Apr 2021

A Microbiota-Directed Food Intervention For Undernourished Children, Robert Y Chen, Matthew C Hibberd, Arjun S Raman, Daniel Webber, Cyrus Zhou, Vinaik Sundaresan, Kazi Ahsan, Martin F Meier, Michael J Barratt, Jeffrey I Gordon, Et Al

Open Access Publications

BACKGROUND: More than 30 million children worldwide have moderate acute malnutrition. Current treatments have limited effectiveness, and much remains unknown about the pathogenesis of this condition. Children with moderate acute malnutrition have perturbed development of their gut microbiota.

METHODS: In this study, we provided a microbiota-directed complementary food prototype (MDCF-2) or a ready-to-use supplementary food (RUSF) to 123 slum-dwelling Bangladeshi children with moderate acute malnutrition between the ages of 12 months and 18 months. The supplementation was given twice daily for 3 months, followed by 1 month of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age z scores and mid-upper-arm circumference …


Optimized Polyepitope Neoantigen Dna Vaccines Elicit Neoantigen-Specific Immune Responses In Preclinical Models And In Clinical Translation, Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W Kim, John M Herndon, Michelle K Becker-Hapak, Beatriz M Carreno, Nancy B Myers, Mark A Sturmoski, Michael D Mclellan, Christopher A Miller, Tanner M Johanns, Benjamin R Tan, Gavin P Dunn, Timothy P Fleming, Ted H Hansen, S Peter Goedegebuure, William E Gillanders Apr 2021

Optimized Polyepitope Neoantigen Dna Vaccines Elicit Neoantigen-Specific Immune Responses In Preclinical Models And In Clinical Translation, Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W Kim, John M Herndon, Michelle K Becker-Hapak, Beatriz M Carreno, Nancy B Myers, Mark A Sturmoski, Michael D Mclellan, Christopher A Miller, Tanner M Johanns, Benjamin R Tan, Gavin P Dunn, Timothy P Fleming, Ted H Hansen, S Peter Goedegebuure, William E Gillanders

2020-Current year OA Pubs

BACKGROUND: Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation.

METHODS: We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer …


Dorsal Anterior Cingulate Cortex Encodes The Integrated Incentive Motivational Value Of Cognitive Task Performance, Debbie M Yee, Jennifer L Crawford, Bidhan Lamichhane, Todd S Braver Apr 2021

Dorsal Anterior Cingulate Cortex Encodes The Integrated Incentive Motivational Value Of Cognitive Task Performance, Debbie M Yee, Jennifer L Crawford, Bidhan Lamichhane, Todd S Braver

2020-Current year OA Pubs

Humans can seamlessly combine value signals from diverse motivational incentives, yet it is not well understood how these signals are "bundled" in the brain to modulate cognitive control. The dorsal ACC (dACC) is theorized to integrate motivational value dimensions in the service of goal-directed action, although this hypothesis has yet to receive rigorous confirmation. In the present study, we examined the role of human dACC in motivational incentive integration. Healthy young adult men and women were scanned with fMRI while engaged in an experimental paradigm that quantifies the combined effects of liquid (e.g., juice, neutral, saltwater) and monetary incentives on …


Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon Apr 2021

Functional Interpretation Of Atad3a Variants In Neuro-Mitochondrial Phenotypes, Zheng Yie Yap, Yo Han Park, Saskia B Wortmann, Adam C Gunning, Shlomit Ezer, Sukyeong Lee, Lita Duraine, Ekkehard Wilichowski, Kate Wilson, Johannes A Mayr, Matias Wagner, Hong Li, Usha Kini, Emily Davis Black, Kristin G Monaghan, James R Lupski, Sian Ellard, Dominik S Westphal, Tamar Harel, Wan Hee Yoon

Faculty, Staff and Students Publications

BACKGROUND: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

METHODS: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. A Drosophila Atad3a Gal4 …


Dietary Intake Is Associated With Neuropsychological Impairment In Women With Hiv, Leah H. Rubin, Deborah R. Gustafson, Lakshmi Warrior, Lila Sheira, Kathryn C. Fitzgerald, Raha Dastgheyb, Kathleen M. Weber, Phyllis C. Tien, Audrey French, Amanda B. Spence, Anjali Sharma, Dionna W. Williams, Cory J. White, Eric C. Seaberg, Edward A. Frongillo Jr., Sheri D. Weiser Apr 2021

Dietary Intake Is Associated With Neuropsychological Impairment In Women With Hiv, Leah H. Rubin, Deborah R. Gustafson, Lakshmi Warrior, Lila Sheira, Kathryn C. Fitzgerald, Raha Dastgheyb, Kathleen M. Weber, Phyllis C. Tien, Audrey French, Amanda B. Spence, Anjali Sharma, Dionna W. Williams, Cory J. White, Eric C. Seaberg, Edward A. Frongillo Jr., Sheri D. Weiser

Faculty Publications

Background

Diet is a modifiable risk factor that may influence cognition in people with HIV.

Objectives

We examined the association between dietary intake and cognition in women with HIV (WWH) and HIV-seronegative women.

Methods

An 18-item dietary National Cancer Institute screener was completed by 729 WWH and 346 HIV-seronegative Women's Interagency HIV Study participants. Daily intake frequencies of processed meats, sweet beverages, fish, whole milk, and vegetables were calculated. Participants completed biennial neuropsychological (NP) testing. NP domains included attention/working memory, executive function, processing speed, memory, learning, fluency, and motor function. NP impairment was defined as demographically adjusted T-scores (mean = …


The Structure, Function And Evolution Of A Complete Human Chromosome 8, Glennis A Logsdon, Milinn Kremitzki, Tina A Graves-Lindsay, Et Al Apr 2021

The Structure, Function And Evolution Of A Complete Human Chromosome 8, Glennis A Logsdon, Milinn Kremitzki, Tina A Graves-Lindsay, Et Al

Open Access Publications

The complete assembly of each human chromosome is essential for understanding human biology and evolution


Uterine Contractions In Rodent Models And Humans, Manasi Malik, Michelle Roh, Sarah K England Apr 2021

Uterine Contractions In Rodent Models And Humans, Manasi Malik, Michelle Roh, Sarah K England

2020-Current year OA Pubs

Aberrant uterine contractions can lead to preterm birth and other labour complications and are a significant cause of maternal morbidity and mortality. To investigate the mechanisms underlying dysfunctional uterine contractions, researchers have used experimentally tractable small animal models. However, biological differences between humans and rodents change how researchers select their animal model and interpret their results. Here, we provide a general review of studies of uterine excitation and contractions in mice, rats, guinea pigs, and humans, in an effort to introduce new researchers to the field and help in the design and interpretation of experiments in rodent models.


Hypoxia-Inducible Factor–1Α–Dependent Induction Of Mir122 Enhances Hepatic Ischemia Tolerance, Cynthia Ju, Meng Wang, Eunyoung Tak, Boyun Kim, Christoph Emontzpohl, Yang Yang, Xiaoyi Yuan, Huban Kutay, Yafen Liang, David R Hall, Wasim A Dar, J Steve Bynon, Peter Carmeliet, Kalpana Ghoshal, Holger K Eltzschig Apr 2021

Hypoxia-Inducible Factor–1Α–Dependent Induction Of Mir122 Enhances Hepatic Ischemia Tolerance, Cynthia Ju, Meng Wang, Eunyoung Tak, Boyun Kim, Christoph Emontzpohl, Yang Yang, Xiaoyi Yuan, Huban Kutay, Yafen Liang, David R Hall, Wasim A Dar, J Steve Bynon, Peter Carmeliet, Kalpana Ghoshal, Holger K Eltzschig

Faculty, Staff and Student Publications

Hepatic ischemia and reperfusion (IR) injury contributes to the morbidity and mortality associated with liver transplantation. microRNAs (miRNAs) constitute a family of noncoding RNAs that regulate gene expression at the posttranslational level through the repression of specific target genes. Here, we hypothesized that miRNAs could be targeted to enhance hepatic ischemia tolerance. A miRNA screen in a murine model of hepatic IR injury pointed us toward the liver-specific miRNA miR122. Subsequent studies in mice with hepatocyte-specific deletion of miR122 (miR122loxP/loxP Alb-Cre+ mice) during hepatic ischemia and reperfusion revealed exacerbated liver injury. Transcriptional studies implicated hypoxia-inducible factor-1α (HIF1α) in the induction …


Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun Apr 2021

Rev-Erb In Gabaergic Neurons Controls Diurnal Hepatic Insulin Sensitivity, Guolian Ding, Xin Li, Xinguo Hou, Wenjun Zhou, Yingyun Gong, Fuqiang Liu, Yanlin He, Jia Song, Jing Wang, Paul Basil, Wenbo Li, Sichong Qian, Pradip Saha, Jinbang Wang, Chen Cui, Tingting Yang, Kexin Zou, Younghun Han, Christopher I Amos, Yong Xu, Li Chen, Zheng Sun

Faculty, Staff and Students Publications

Systemic insulin sensitivity shows diurnal rhythm with a peak at wakening1,2. The molecular mechanism underlying such a temporal pattern is unclear. Here we demonstrate that nuclear receptors Rev-erbα/β in the GABAergic neurons in the suprachiasmatic nucleus (SCNGABA) control the diurnal rhythm of insulin-mediated suppression of hepatic glucose production in mice, without affecting diurnal eating or locomotor behaviors under the regular light-dark cycles. Rev-erb regulates the rhythmic expression of genes involved in neurotransmission in the SCN and modulates the oscillatory firing activity of SCNGABA neurons. Chemogenetic stimulation of SCNGABA neurons at wakening causes glucose intolerance, while restoration …


Myocardial T1 And T2 Mapping By Magnetic Resonance In Patients With Immune Checkpoint Inhibitor-Associated Myocarditis., Paaladinesh Thavendiranathan, Lili Zhang, Amna Zafar, Zsofia D Drobni, Syed S Mahmood, Marcella Cabral, Magid Awadalla, Anju Nohria, Daniel A Zlotoff, Franck Thuny, Lucie M Heinzerling, Ana Barac, Ryan J Sullivan, Carol L Chen, Dipti Gupta, Michael C Kirchberger, Sarah E Hartmann, Jonathan W Weinsaft, Hannah K Gilman, Muhammad A. Rizvi Md, Bojan Kovacina, Caroline Michel, Gagan Sahni, Ana González-Mansilla, Antonio Calles, Francisco Fernández-Avilés, Michael Mahmoudi, Kerry L Reynolds, Sarju Ganatra, Juan José Gavira, Nahikari Salterain González, Manuel García De Yébenes Castro, Raymond Y Kwong, Michael Jerosch-Herold, Otavio R Coelho-Filho, Jonathan Afilalo, Eduardo Zataraín-Nicolás, A John Baksi, Bernd J Wintersperger, Oscar Calvillo-Arguelles, Stephane Ederhy, Eric H Yang, Alexander R Lyon, Michael G Fradley, Tomas G Neilan Mar 2021

Myocardial T1 And T2 Mapping By Magnetic Resonance In Patients With Immune Checkpoint Inhibitor-Associated Myocarditis., Paaladinesh Thavendiranathan, Lili Zhang, Amna Zafar, Zsofia D Drobni, Syed S Mahmood, Marcella Cabral, Magid Awadalla, Anju Nohria, Daniel A Zlotoff, Franck Thuny, Lucie M Heinzerling, Ana Barac, Ryan J Sullivan, Carol L Chen, Dipti Gupta, Michael C Kirchberger, Sarah E Hartmann, Jonathan W Weinsaft, Hannah K Gilman, Muhammad A. Rizvi Md, Bojan Kovacina, Caroline Michel, Gagan Sahni, Ana González-Mansilla, Antonio Calles, Francisco Fernández-Avilés, Michael Mahmoudi, Kerry L Reynolds, Sarju Ganatra, Juan José Gavira, Nahikari Salterain González, Manuel García De Yébenes Castro, Raymond Y Kwong, Michael Jerosch-Herold, Otavio R Coelho-Filho, Jonathan Afilalo, Eduardo Zataraín-Nicolás, A John Baksi, Bernd J Wintersperger, Oscar Calvillo-Arguelles, Stephane Ederhy, Eric H Yang, Alexander R Lyon, Michael G Fradley, Tomas G Neilan

Hematology-Medical Oncology Division

BACKGROUND: Myocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited.

OBJECTIVES: This study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis.

METHODS: In this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major …


Opioids Are Not A Major Cause Of Death Of Patients With Sickle Cell Disease., Samir K. Ballas Mar 2021

Opioids Are Not A Major Cause Of Death Of Patients With Sickle Cell Disease., Samir K. Ballas

Cardeza Foundation for Hematologic Research

According to the Center of Disease Control and Prevention (CDC) database, the total number of deaths due to opioid overdose from 1999 through 2018 was 840,629. Given the alarming nature of these statistics, patients who requested prescription for opioids became targets of suspicion and possible accusation of maladaptive behavior. Patients with sickle cell disease (SCD) were often not exempt from such accusations and became guilty by association. In order to clarify the effect of opioids on the mortality of patients with SCD, the mortality rates for children and adults with SCD were investigated using the CDC Wide-ranging Online Data for …


Characteristics And Comparative Clinical Outcomes Of Prisoner Versus Non-Prisoner Populations Hospitalized With Covid-19, Ahmed M. Altibi, Bhargava Pallavi, Hassan Liaqat, Alexander A. Slota, Radhika Sheth, Lama N. Al Jebbawi, Matt E. George, Allison Leduc, Enas Abdallah, Luke R. Russell, Saniya Jain, Nariné Shirvanian, Ahmad Masri, Vivek Kak Mar 2021

Characteristics And Comparative Clinical Outcomes Of Prisoner Versus Non-Prisoner Populations Hospitalized With Covid-19, Ahmed M. Altibi, Bhargava Pallavi, Hassan Liaqat, Alexander A. Slota, Radhika Sheth, Lama N. Al Jebbawi, Matt E. George, Allison Leduc, Enas Abdallah, Luke R. Russell, Saniya Jain, Nariné Shirvanian, Ahmad Masri, Vivek Kak

Internal Medicine Articles

Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were …


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


Insulinase-Like Protease 1 Contributes To Macrogamont Formation In Cryptosporidium Parvum, Rui Xu, Yaoyu Feng, Lihua Xiao, L David Sibley Mar 2021

Insulinase-Like Protease 1 Contributes To Macrogamont Formation In Cryptosporidium Parvum, Rui Xu, Yaoyu Feng, Lihua Xiao, L David Sibley

Open Access Publications

The apicomplexan parasite


The Transcription Factor Pdr802 Regulates Titan Cell Formation And Pathogenicity Of Cryptococcus Neoformans, Julia C V Reuwsaat, Daniel P Agustinho, Heryk Motta, Andrew L Chang, Holly Brown, Michael R Brent, Livia Kmetzsch, Tamara L Doering Mar 2021

The Transcription Factor Pdr802 Regulates Titan Cell Formation And Pathogenicity Of Cryptococcus Neoformans, Julia C V Reuwsaat, Daniel P Agustinho, Heryk Motta, Andrew L Chang, Holly Brown, Michael R Brent, Livia Kmetzsch, Tamara L Doering

Open Access Publications

No abstract provided.


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.