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The Effects Of Progesterone Induced Blocking Factor And 17-Hydroxyprogesterone Caproate On The Pathophysiology Of Preeclampsia, Kyleigh M. Comley 2021 University of Mississippi

The Effects Of Progesterone Induced Blocking Factor And 17-Hydroxyprogesterone Caproate On The Pathophysiology Of Preeclampsia, Kyleigh M. Comley

Honors Theses

Preeclampsia (PE) is responsible for about 20% of the 13 million preterm births each year worldwide, including 100,000 cases annually in the United States. Despite being a leading cause of maternal and perinatal morbidity, the mechanisms of pathogenesis are still largely unknown. PE is progesterone deficient state characterized by hypertension, chronic immune activation, endothelial dysfunction and severe forms can lead to seizures. Treatment of seizures includes the administration of magnesium sulfate (MgSO4) though not all PE patients are responsive, and it does not decrease PE-associated hypertension. To resolve these conditions, PE patients are delivered early thereby making PE the ...


Predictors Of Irritability Symptoms In Mildly Depressed Perimenopausal Women, Anouk E. de Wit, Erik J. Giltay, Marrit K. de Boer, Margo Nathan, Aleta Wiley, Sybil L. Crawford, Hadine Joffe 2021 Harvard Medical School

Predictors Of Irritability Symptoms In Mildly Depressed Perimenopausal Women, Anouk E. De Wit, Erik J. Giltay, Marrit K. De Boer, Margo Nathan, Aleta Wiley, Sybil L. Crawford, Hadine Joffe

Graduate School of Nursing Publications

OBJECTIVE: Irritability is a highly burdensome complaint, commonly, but not universally, linked with depressive symptoms. While increased variability in estradiol has been associated with depressive symptoms during perimenopause, more insight is needed into reproductive hormone dynamics and other factors that predispose perimenopausal women to irritable mood.

METHODS: Among 50 mildly depressed perimenopausal women (mean (SD) age 48.4 (3.9) years), severity of irritability symptoms (on Symptom Questionnaire Hostility subscale, range 0-23) was assessed weekly for eight weeks, concurrent with potential predictors. Associations between these were examined using generalized estimating equating models.

RESULTS: Most women (82.0%) reported having moderate ...


A Feed-Forward Regulatory Loop In Adipose Tissue Promotes Signaling By The Hepatokine Fgf21, Myoung Souk Han, Rachel J. Perry, Joao-Paulo Camporez, Philipp E. Scherer, Gerald I. Shulman, Guangping Gao, Roger J. Davis 2021 University of Massachusetts Medical School

A Feed-Forward Regulatory Loop In Adipose Tissue Promotes Signaling By The Hepatokine Fgf21, Myoung Souk Han, Rachel J. Perry, Joao-Paulo Camporez, Philipp E. Scherer, Gerald I. Shulman, Guangping Gao, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is activated by metabolic stress and promotes the development of metabolic syndrome, including hyperglycemia, hyperlipidemia, and insulin resistance. This integrated physiological response involves cross-talk between different organs. Here we demonstrate that JNK signaling in adipocytes causes an increased circulating concentration of the hepatokine fibroblast growth factor 21 (FGF21) that regulates systemic metabolism. The mechanism of organ crosstalk is mediated by a feed-forward regulatory loop caused by JNK-regulated FGF21 autocrine signaling in adipocytes that promotes increased expression of the adipokine adiponectin and subsequent hepatic expression of the hormone FGF21. The mechanism of organ cross-talk ...


Internet Transparency Of Local Men’S Health Clinics In Nebraska, Jinfeng Jiang, Jordan Stegman, Christopher M. Deibert 2020 University of Nebraska Medical Center, College of Medicine

Internet Transparency Of Local Men’S Health Clinics In Nebraska, Jinfeng Jiang, Jordan Stegman, Christopher M. Deibert

Graduate Medical Education Research Journal

An overview of Men’s Health Clinics offering Testosterone Therapy in a Midwest State.

Introduction/ Background – Since 2001, there has been a 300% increase in the use of Testosterone therapy. However, there remains limited published data on the demographics of facilities and providers that advertise this service. This study aims to look at such demographics of advertised Men’s health clinics in Nebraska.

Methods/ Materials – An internet search was conducted with the phrases “Nebraska Male health clinics, Nebraska Low T/testosterone, Nebraska Hormone Replacement Therapy”. All clinics that were found offering Testosterone therapy with Men’s health in their mission ...


Evaluating The Association Between Vasopressin Use And In-Hospital Mortality In Patients With Septic Shock, Michael Pasqualicchio, Heidi Clarke, Jonathan Kline, Payal Patel 2020 Baptist Hospital of Miami

Evaluating The Association Between Vasopressin Use And In-Hospital Mortality In Patients With Septic Shock, Michael Pasqualicchio, Heidi Clarke, Jonathan Kline, Payal Patel

All Publications

No abstract provided.


Characterization Of Viral Insulins Reveals White Adipose Tissue-Specific Effects In Mice, Martina Chrudinova, Francois Moreau, Hye Lim Noh, Terezie Panikova, Lenka Zakova, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis 2020 Boston College

Characterization Of Viral Insulins Reveals White Adipose Tissue-Specific Effects In Mice, Martina Chrudinova, Francois Moreau, Hye Lim Noh, Terezie Panikova, Lenka Zakova, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis

Open Access Publications by UMMS Authors

OBJECTIVE: Members of the insulin/insulin-like growth factor (IGF) superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single-chain (sc), i.e., IGF-1-like, forms of the viral insulin/IGF-1-like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e., more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis ...


Roles Of Adipokines In Digestive Diseases: Markers Of Inflammation, Metabolic Alteration And Disease Progression, Ming-Ling Chang, Zinger Yang, Sien-Sing Yang 2020 Chang Gung University

Roles Of Adipokines In Digestive Diseases: Markers Of Inflammation, Metabolic Alteration And Disease Progression, Ming-Ling Chang, Zinger Yang, Sien-Sing Yang

Open Access Publications by UMMS Authors

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related ...


Myxedema Coma: A Life-Threatening Condition In Patients Using Pembrolizumab, Sangeetha Gummalla, Madhura Manjunath, Brian Phillips 2020 Berkshire Medical Center

Myxedema Coma: A Life-Threatening Condition In Patients Using Pembrolizumab, Sangeetha Gummalla, Madhura Manjunath, Brian Phillips

Open Access Publications by UMMS Authors

The advent of immune checkpoint inhibitors has significantly improved the prognosis of patients with advanced malignancies. As we begin to understand these medications, multiple immune-related adverse effects (irAEs) have been found with these drugs, including endocrinopathies. Understanding the treatment-related adverse events of these medications is critical for clinical practice. Thyroid-related adverse effects usually occur within the first three months of treatment and rarely after eight months. It can manifest as an early onset of thyrotoxicosis, which is largely asymptomatic, followed by a rapid transition to hypothyroidism, requiring long-term levothyroxine substitution. We present a case in which our patient was found ...


Coxsackievirus B Type 4 Infection In Beta Cells Downregulates The Chaperone Prefoldin Uri To Induce A Mody4-Like Diabetes Via Pdx1 Silencing, Hugo Bernard, Ana Teijeiro, Almudena Chaves-Perez, Cristian Perna, Basanthi Satish, Anna Novials, Jennifer P. Wang, Nabil Djouder 2020 National Cancer Research Center

Coxsackievirus B Type 4 Infection In Beta Cells Downregulates The Chaperone Prefoldin Uri To Induce A Mody4-Like Diabetes Via Pdx1 Silencing, Hugo Bernard, Ana Teijeiro, Almudena Chaves-Perez, Cristian Perna, Basanthi Satish, Anna Novials, Jennifer P. Wang, Nabil Djouder

University of Massachusetts Medical School Faculty Publications

Enteroviruses are suspected to contribute to insulin-producing beta cell loss and hyperglycemia-induced diabetes. However, mechanisms are not fully defined. Here, we show that coxsackievirus B type 4 (CVB4) infection in human islet-engrafted mice and in rat insulinoma cells displays loss of unconventional prefoldin RPB5 interactor (URI) and PDX1, affecting beta cell function and identity. Genetic URI ablation in the mouse pancreas causes PDX1 depletion in beta cells. Importantly, diabetic PDX1 heterozygous mice overexpressing URI in beta cells are more glucose tolerant. Mechanistically, URI loss triggers estrogen receptor nuclear translocation leading to DNA methyltransferase 1 (DNMT1) expression, which induces Pdx1 promoter ...


Beta-Cell Specific Insulin Resistance Promotes Glucose-Stimulated Insulin Hypersecretion [Preprint], Søs Skovsø, Hye Lim Noh, Sujin Suk, Brian Gablaski, Jason K. Kim, James D. Johnson 2020 University of British Columbia

Beta-Cell Specific Insulin Resistance Promotes Glucose-Stimulated Insulin Hypersecretion [Preprint], Søs Skovsø, Hye Lim Noh, Sujin Suk, Brian Gablaski, Jason K. Kim, James D. Johnson

University of Massachusetts Medical School Faculty Publications

Insulin receptor (Insr) protein can be found at higher levels in pancreatic β-cells than in most other cell types, but the consequences of β-cell insulin resistance remain enigmatic. Ins1cre allele was used to delete Insr specifically in β-cells of both female and male mice which were compared to Ins1cre-containing littermate controls at multiple ages and on multiple diets. RNA-seq of recombined β-cells revealed significant differences in multiple pathways previously implicated in insulin secretion and cellular fate, including rewired Ras and NFκB signaling. Male, but not female, βInsrKO mice had reduced oxygen consumption rate, while action ...


Crispr-Enhanced Human Adipocyte 'Browning' As Cell Therapy For Metabolic Disease [Preprint], Emmanouela Tsagkaraki, Sarah M. Nicoloro, Tiffany DeSouza, Javier Solivan-Rivera, Anand Desai, Yuefei Shen, Mark Kelly, Adilson L. Guilherme, Felipe Henriques, Raed Ibraheim, Nadia Amrani, Kevin Luk, Stacy Maitland, Randall H. Friedline, Lauren Tauer, Xiaodi Hu, Jason K. Kim, Scot A. Wolfe, Erik J. Sontheimer, Silvia Corvera, Michael P. Czech 2020 University of Massachusetts Medical School

Crispr-Enhanced Human Adipocyte 'Browning' As Cell Therapy For Metabolic Disease [Preprint], Emmanouela Tsagkaraki, Sarah M. Nicoloro, Tiffany Desouza, Javier Solivan-Rivera, Anand Desai, Yuefei Shen, Mark Kelly, Adilson L. Guilherme, Felipe Henriques, Raed Ibraheim, Nadia Amrani, Kevin Luk, Stacy Maitland, Randall H. Friedline, Lauren Tauer, Xiaodi Hu, Jason K. Kim, Scot A. Wolfe, Erik J. Sontheimer, Silvia Corvera, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

Obesity and type 2 diabetes (T2D) are associated with poor tissue responses to insulin [1,2], disturbances in glucose and lipid fluxes [3-5] and comorbidities including steatohepatitis [6] and cardiovascular disease [7,8]. Despite extensive efforts at prevention and treatment [9,10], diabetes afflicts over 400 million people worldwide [11]. Whole body metabolism is regulated by adipose tissue depots [12-14], which include both lipid-storing white adipocytes and less abundant 'brown' and 'brite/beige' adipocytes that express thermogenic uncoupling protein UCP1 and secrete factors favorable to metabolic health [15-18]. Application of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing [19 ...


Caenorhabditis Elegans Methionine/S-Adenosylmethionine Cycle Activity Is Sensed And Adjusted By A Nuclear Hormone Receptor, Gabrielle E. Giese, Melissa D. Walker, Olga Ponomarova, Hefei Zhang, Xuhang Li, Gregory Minevich, Albertha J. M. Walhout 2020 University of Massachusetts Medical School

Caenorhabditis Elegans Methionine/S-Adenosylmethionine Cycle Activity Is Sensed And Adjusted By A Nuclear Hormone Receptor, Gabrielle E. Giese, Melissa D. Walker, Olga Ponomarova, Hefei Zhang, Xuhang Li, Gregory Minevich, Albertha J. M. Walhout

Open Access Publications by UMMS Authors

Vitamin B12 is an essential micronutrient that functions in two metabolic pathways: the canonical propionate breakdown pathway and the methionine/S-adenosylmethionine (Met/SAM) cycle. In Caenorhabditis elegans, low vitamin B12, or genetic perturbation of the canonical propionate breakdown pathway results in propionate accumulation and the transcriptional activation of a propionate shunt pathway. This propionate-dependent mechanism requires nhr-10 and is referred to as 'B12-mechanism-I'. Here, we report that vitamin B12 represses the expression of Met/SAM cycle genes by a propionate-independent mechanism we refer to as 'B12-mechanism-II'. This mechanism is activated by perturbations in the Met/SAM cycle, genetically or due ...


Contraceptive Methods In The United States: The Question Of Abortive Mechanisms, Tara Ferenczy 2020 Liberty University

Contraceptive Methods In The United States: The Question Of Abortive Mechanisms, Tara Ferenczy

Senior Honors Theses

This thesis reviews the many methods of contraception available in the United States. Although society’s understanding of women’s health has become a major topic, there is still a significant deficit of information regarding how the accessible methods affect women’s bodies, specifically reproductive tissue. The thesis analyzes numerous contraceptive options focusing specifically on the mechanisms of action to determine whether options have abortifacient properties so that readers may develop educated opinions regarding medical and ethical uses. Information involving strengths and limitations of each technique and the effects on both the female body and the reproductive material assist in ...


Melatonin Patterns And Levels During The Human Menstrual Cycle And After Menopause, Gail A. Greendale, Paula Witt-Enderby, Arun S. Karlamangla, Fahima Munmun, Sybil L. Crawford, MeiHua Huang, Nanette Santoro 2020 University of California, Los Angeles

Melatonin Patterns And Levels During The Human Menstrual Cycle And After Menopause, Gail A. Greendale, Paula Witt-Enderby, Arun S. Karlamangla, Fahima Munmun, Sybil L. Crawford, Meihua Huang, Nanette Santoro

Graduate School of Nursing Publications

Context: Melatonin may play a role in the regulation of the human menstrual cycle and may decline with menopause and/or aging.

Objective: The objective of this work is to investigate the relations between melatonin and the menstrual cycle, menopause, and aging.

Methods: This was a cross-sectional and longitudinal analysis of 20 participants from the Study of Women's Health Across the Nation (SWAN) Daily Hormone Study (DHS). The outcome measure was first-morning urine assay of 6-sulfatoxymelatonin (aMT6s), a gauge of melatonin. For each participant, aMT6s was measured daily during one premenopausal cycle with evidence of luteal activity (ELA) and ...


Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice [Preprint], Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis 2020 Boston College

Characterization Of Viral Insulins Reveals White Adipose Tissue Specific Effects In Mice [Preprint], Martina Chrudinová, Francois Moreau, Hye Lim Noh, Terezie Páníková, Lenka Žáková, Randall H. Friedline, Francisco A. Valenzuela, Jason K. Kim, Jiri Jiracek, C. Ronald Kahn, Emrah Altindis

University of Massachusetts Medical School Faculty Publications

Members of the insulin/IGF superfamily are well conserved across the evolutionary tree. We recently showed that four viruses in the Iridoviridae family possess genes that encode proteins highly homologous to human insulin/IGF-1. Using chemically synthesized single chain (sc), i.e. IGF-1-like, forms of the viral insulin/IGF-1 like peptides (VILPs), we previously showed that they can stimulate human receptors. Because these peptides possess potential cleavage sites to form double chain (dc), i.e. more insulin-like, VILPs, in this study, we have characterized dc forms of VILPs for Grouper iridovirus (GIV), Singapore grouper iridovirus (SGIV) and Lymphocystis disease virus-1 ...


Luteinizing Hormone Action In Human Oocyte Maturation And Quality: Signaling Pathways, Regulation, And Clinical Impact, Armando Arroyo, Beomsu Kim, John Yeh 2020 SUNY Upstate Medical University

Luteinizing Hormone Action In Human Oocyte Maturation And Quality: Signaling Pathways, Regulation, And Clinical Impact, Armando Arroyo, Beomsu Kim, John Yeh

Open Access Publications by UMMS Authors

The ovarian follicle luteinizing hormone (LH) signaling molecules that regulate oocyte meiotic maturation have recently been identified. The LH signal reduces preovulatory follicle cyclic nucleotide levels which releases oocytes from the first meiotic arrest. In the ovarian follicle, the LH signal reduces cyclic nucleotide levels via the CNP/NPR2 system, the EGF/EGF receptor network, and follicle/oocyte gap junctions. In the oocyte, reduced cyclic nucleotide levels activate the maturation promoting factor (MPF). The activated MPF induces chromosome segregation and completion of the first and second meiotic divisions. The purpose of this paper is to present an overview of the ...


Control Of Adipocyte Thermogenesis And Lipogenesis Through Beta3-Adrenergic And Thyroid Hormone Signal Integration, Adilson L. Guilherme, Batuhan Yenilmez, Alexander H. Bedard, Felipe Henriques, Dianxin Liu, Alexandra Lee, Lauren Goldstein, Mark Kelly, Sarah M. Nicoloro, Min Chen, Lee Weinstein, Sheila Collins, Michael P. Czech 2020 University of Massachusetts Medical School

Control Of Adipocyte Thermogenesis And Lipogenesis Through Beta3-Adrenergic And Thyroid Hormone Signal Integration, Adilson L. Guilherme, Batuhan Yenilmez, Alexander H. Bedard, Felipe Henriques, Dianxin Liu, Alexandra Lee, Lauren Goldstein, Mark Kelly, Sarah M. Nicoloro, Min Chen, Lee Weinstein, Sheila Collins, Michael P. Czech

Open Access Publications by UMMS Authors

Here, we show that beta adrenergic signaling coordinately upregulates de novo lipogenesis (DNL) and thermogenesis in subcutaneous white adipose tissue (sWAT), and both effects are blocked in mice lacking the cAMP-generating G protein-coupled receptor Gs (Adipo-GsalphaKO) in adipocytes. However, UCP1 expression but not DNL activation requires rapamycin-sensitive mTORC1. Furthermore, beta3-adrenergic agonist CL316243 readily upregulates thermogenic but not lipogenic genes in cultured adipocytes, indicating that additional regulators must operate on DNL in sWAT in vivo. We identify one such factor as thyroid hormone T3, which is elevated locally by adrenergic signaling. T3 administration to wild-type mice enhances both thermogenesis and DNL ...


The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers 2020 University of San Diego

The Role Of Dopamine In Decision Making Processes In Drosophila Melanogaster, Michelle C. Bowers

Undergraduate Honors Theses

Understanding the neural processes that mediate decision making is a relatively new field of investigation in the scientific community. With the ultimate goal of understanding how humans decide between one path and another, simpler models such as Drosophila Melanogaster, the common fruit fly, are often utilized as a way of determining the neural circuits involved in these decision-making processes. One of the most important decisions flies make is the decision of where to lay their eggs (oviposit). Choosing the proper substrate upon which to lay eggs is a crucial decision that can ultimately impact their fecundity. This paper investigates the ...


Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech 2020 University of Massachusetts Medical School

Mechanisms Of Insulin Resistance Related To White, Beige, And Brown Adipocytes, Michael P. Czech

Open Access Publications by UMMS Authors

BACKGROUND: The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with glucose intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses on the molecular and cellular disruptions that contribute to the syndrome. However, significant uncertainty remains on the mechanisms of its initiation and long-term maintenance.

SCOPE OF REVIEW: To simplify insulin resistance analysis, this review focuses on the unifying concept that adipose tissue is a central regulator of systemic glucose homeostasis by controlling liver and skeletal muscle metabolism. Key aspects of adipose function related to insulin resistance ...


Exogenous Gdf11, But Not Gdf8, Reduces Body Weight And Improves Glucose Homeostasis In Mice, Ryan G. Walker, Hye Lim Noh, Taekyoon Kim, Jason K. Kim, Richard T. Lee 2020 Harvard University

Exogenous Gdf11, But Not Gdf8, Reduces Body Weight And Improves Glucose Homeostasis In Mice, Ryan G. Walker, Hye Lim Noh, Taekyoon Kim, Jason K. Kim, Richard T. Lee

Open Access Publications by UMMS Authors

Insulin resistance is associated with aging in mice and humans. We have previously shown that administration of recombinant GDF11 (rGDF11) to aged mice alters aging phenotypes in the brain, skeletal muscle, and heart. While the closely related protein GDF8 has a role in metabolism, limited data are available on the potential metabolic effects of GDF11 or GDF8 in aging. To determine the metabolic effects of these two ligands, we administered rGDF11 or rGDF8 protein to young or aged mice fed a standard chow diet, short-term high-fat diet (HFD), or long-term HFD. Under nearly all of these diet conditions, administration of ...


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