Medicine and Health Sciences Commons^™

The Feigned Annoyance And Frustration Test To Activate The Sympathoadrenal Medullary System, Ted W. Gehrig Iii, Lee S. Berk, Robert I. Dudley, Jo A. Smith, Lida Gharibvand, Everett B. Lohman Iii

Physical Therapy Faculty Articles and Research

When perceived as threatening, social interactions have been shown to trigger the sympathoadrenal medullary system as well as the hypothalamic-pituitary-adrenal axis resulting in a physiologic stress response. The allostatic load placed on human health and physiology in the context of acute and chronic stress can have profound health consequences. The purpose of this study was to develop a protocol for a lab-based stress stimulus using social-evaluative threat. While several valid, stress-stimulating protocols exist, we sought to develop one that triggered a physiologic response, did not require significant lab resources, and could be completed in around 10 min. We included 53 …

Targeted Next-Generation Sequencing Of Congenital Hypothyroidism-Causative Genes Reveals Unexpected Thyroglobulin Gene Variants In Patients With Iodide Transport Defect, Carlos Eduardo Bernal Barquero, Romina Celeste Geysels, Virginie Jacques, Gerardo Hérnan Carro, Mariano Martín, Victoria Peyret, María Celeste Abregú, Patricia Papendieck, Ana María Masini-Repiso, Frédérique Savagner, Ana Elena Chiesa, Cintia E. Citterio, Juan Pablo Nicola

Pharmacy Faculty Articles and Research

Congenital iodide transport defect is an uncommon autosomal recessive disorder caused by loss-of-function variants in the sodium iodide symporter (NIS)-coding SLC5A5 gene and leading to dyshormonogenic congenital hypothyroidism. Here, we conducted a targeted next-generation sequencing assessment of congenital hypothyroidism-causative genes in a cohort of nine unrelated pediatric patients suspected of having a congenital iodide transport defect based on the absence of 99mTc-pertechnetate accumulation in a eutopic thyroid gland. Although, unexpectedly, we could not detect pathogenic SLC5A5 gene variants, we identified two novel compound heterozygous TG gene variants (p.Q29* and c.177-2A>C), three novel heterozygous TG gene variants (p.F1542Vfs*20, p.Y2563C, and …

Endocrine-Disrupting Chemicals And Breast Cancer: Disparities In Exposure And Importance Of Research Inclusivity, Ashlie Santaliz Casiano, Annah Lee, Dede Teteh, Zeynep Madak Erdogan, Lindsey Trevino

Health Sciences and Kinesiology Faculty Articles

Endocrine-disrupting chemicals (EDCs) are known contributors to breast cancer development. EDC exposures commonly occur through food packaging, cookware, fabrics, and personal care products as well as through the environment. Increasing evidence highlights disparities in EDC exposure across racial/ethnic groups, yet breast cancer research continues to lack the inclusion necessary to positively impact treatment response and overall survival in these socially disadvantaged populations. Additionally, the inequity in environmental exposures has yet to be remedied. Exposure to EDCs due to structural racism poses an unequivocal risk to marginalized communities. In this review, we summarize recent epidemiological and molecular studies on two lesser-studied …

Thyroid Hormone Synthesis Continues Despite Biallelic Thyroglobulin Mutation With Cell Death, Xiaohan Zhang, Aaron P. Kellogg, Cintia E. Citterio, Hao Zhang, Dennis Larkin, Yoshiaki Morishita, Héctor M. Targovnik, Viviana A. Balbi, Peter Arvan

Pharmacy Faculty Articles and Research

Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe …

Actividades Profesionales Reservadas En Argentina: Orígenes Y Actualidad / Reserved Professional Activities In Argentina: Origins And Current Situation, Cintia E. Citterio, Héctor Targovnik

Pharmacy Faculty Articles and Research

En Argentina, la Ley de Educación Superior (LES; Ley 24.521, 1995) establece que hay profesiones cuyo ejercicio puede comprometer el interés público poniendo en riesgo de modo directo la salud, la seguridad, los derechos, los bienes o la formación de los habitantes, y las mismas están contempladas en el artículo 43 de la LES. Sólo aquellas actividades que realicen estos profesionales y que implican un riesgo rigurosamente directo, se denominan actividades profesionales reservadas. Pero… ¿Cuál es la diferencia entre actividades profesionales reservadas y alcances de los títulos? ¿Y cómo se establecen? El objetivo de este trabajo es analizar el significado …

The Role Of Thyroglobulin In Thyroid Hormonogenesis, Cintia E. Citterio, Héctor M. Targovnik, Peter Arvan

Pharmacy Faculty Articles and Research

In humans, the thyroid hormones T₃ and T₄ are synthesized in the thyroid gland in a process that crucially involves the iodoglycoprotein thyroglobulin. The overall structure of thyroglobulin is conserved in all vertebrates. Upon thyroglobulin delivery from thyrocytes to the follicular lumen of the thyroid gland via the secretory pathway, multiple tyrosine residues can become iodinated to form mono-iodotyrosine (MIT) and/or di-iodotyrosine (DIT); however, selective tyrosine residues lead to preferential formation of T₄ and T₃ at distinct sites. T₄ formation involves oxidative coupling between two DIT side chains, and de novo T₃ formation involves …

Relationship Between The Dimerization Of Thyroglobulin And Its Ability To Form Triiodothyronine, Cintia E. Citterio, Yoshiaki Morishita, Nada Dakka, Balaji Veluswamy, Peter Arvan

Pharmacy Faculty Articles and Research

Thyroglobulin (TG) is the most abundant thyroid gland protein, a dimeric iodoglycoprotein (660 kDa). TG serves as the protein precursor in the synthesis of thyroid hormones tetraiodothyronine (T₄) and triiodothyronine (T₃). The primary site for T₃ synthesis in TG involves an iodotyrosine acceptor at the antepenultimate Tyr residue (at the extreme carboxyl terminus of the protein). The carboxyl-terminal region of TG comprises a cholinesterase-like (ChEL) domain followed by a short unique tail sequence. Despite many studies, the monoiodotyrosine donor residue needed for the coupling reaction to create T₃ at this evolutionarily conserved …

Chronic Hypobaric Hypoxia Modulates Primary Cilia Differently In Adult And Fetal Ovine Kidneys, Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T. Sherpa, Rajasekharreddy Pala, Kimberly F. Atkinson, William J. Pearce, Lubo Zhang, Surya M. Nauli

Pharmacy Faculty Articles and Research

Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function. Our results show that although long-term hypoxia induces renal fibrosis in both fetal and adult kidneys, fetal kidneys are more susceptible to …

De Novo Triiodothyronine Formation From Thyrocytes Activated By Thyroid-Stimulating Hormone, Cintia E. Citterio, Balaji Veluswamy, Sarah J. Morgan, Valerie A. Galton, J. Paul Banga, Stephen Atkins, Yoshiaki Morishita, Susanne Neumann, Rauf Latif, Marvin C. Gershengorn, Terry J. Smith, Peter Arvan

Pharmacy Faculty Articles and Research

The thyroid gland secretes primarily tetraiodothyronine (T₄), and some triiodothyronine (T₃). Under normal physiological circumstances, only one-fifth of circulating T₃ is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T₃ toxicosis. Thyroidal T₄ production results from iodination of thyroglobulin (TG) at residues Tyr⁵ and Tyr¹³⁰, whereas thyroidal T₃ production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T₃ is formed …

Actionable Patient Safety Solution (Apss) #3c: Improve Prevention Of Severe Hypoglycemia, Jerika Lam, Steven Barker, Michael Ramsay, Ariana Longley, Joe Kiani

Pharmacy Faculty Articles and Research

This report presents a plan of action for introducing a "program to reduce errors in the recognition and treatment of [severe hypoglycemia]".

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta

Pharmacy Faculty Articles and Research

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5 Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749 residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG gene have been identified and characterized, originating structural changes in the protein that alter the normal protein folding, assembly and …

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siff, Carina M. Rivolta

Pharmacy Faculty Articles and Research

"Congenital hypothyroidism (CH) is the most frequent endocrine disease in infants, affects about 1 in 3,000 newborns and is characterized by elevated levels of thyroidstimulating hormone (TSH) as a consequence of reduced thyroid function. It is also one of the most common preventable causes of cognitive and motor deficits. Prevention of CH is based on carrier identification, genetic counseling and prenatal diagnosis. In neonates a complete diagnosis of CH should include clinical examination, biochemical thyroid tests, thyroid ultrasound, radioiodine or technetium scintigraphy and perchlorate discharge test (PDT). In the last two decades, considerable progress has been made in identifying the …

Regulation Of Polycystin-1 Function By Calmodulin Binding, Nicholas Doerr, Yidi Wang, Kevin R. Kipp, Guangyi Liu, Jesse J. Benza, Vladimir Pletnev, Tengis S. Pavlov, Alexander Staruschenko, Ashraf M. Mohieldin, Maki Takahashi, Surya M. Nauli, Thomas Weimbs

Pharmacy Faculty Articles and Research

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common genetic disease that leads to progressive renal cyst growth and loss of renal function, and is caused by mutations in the genes encoding polycystin-1 (PC1) and polycystin-2 (PC2), respectively. The PC1/PC2 complex localizes to primary cilia and can act as a flow-dependent calcium channel in addition to numerous other signaling functions. The exact functions of the polycystins, their regulation and the purpose of the PC1/PC2 channel are still poorly understood. PC1 is an integral membrane protein with a large extracytoplasmic N-terminal domain and a short, ~200 amino acid C-terminal cytoplasmic tail. …

Antenatal Glucocorticoid Treatment Is Associated With Diurnal Cortisol Regulation In Term-Born Children, M. N. Edelmann, Curt A. Sandman, Laura M. Glynn, D. A. Wing, Elyssia Poggi Davis

Psychology Faculty Articles and Research

Due to the rapid developmental changes that occur during the fetal period, prenatal influences can affect the developing central nervous system with lifelong consequences for physical and mental health. Glucocorticoids are one of the proposed mechanisms by which fetal programing occurs. Glucocorticoids pass through the blood-brain barrier and target receptors throughout the central nervous system. Unlike endogenous glucocorticoids, synthetic glucocorticoids readily pass through the placental barrier to reach the developing fetus. The synthetic glucocorticoid, betamethasone, is routinely given prenatally to mothers at risk for preterm delivery. Over 25% of the fetuses exposed to betamethasone will be born at term. Few …

Intra-Individual Consistency In Endocrine Profiles Across Successive Pregnancies, Molly Fox, Curt A. Sandman, Elyssia Poggi Davis, Laura M. Glynn

Psychology Faculty Articles and Research

Context: It is yet unknown how similar women’s hormone levels are during successive pregnancies, and very little is known about the degree to which siblings experience similar prenatal environments. Given the importance of understanding how women’s reproductive life-histories exert cumulative effects on health via hormone exposure, and the importance of understanding how fetal programming via endocrine signaling affects sibling trait concordance, here we address this important lacuna in the literature.

Objective: To investigate how consistent are women’s hormone profiles across two successive pregnancies.

Design and Main Outcome Measures: This longitudinal, prospective study followed a cohort of 28 …

The Cell's Antenna And Bending With The Flow, Surya M. Nauli, Kimberly F. Atkinson, Sarmed H. Kathem

Pharmacy Faculty Articles and Research

Polycystic kidney disease (PKD) is the most common life-threatening genetic disease worldwide – affecting about 12.5 million people. Patients with the condition have multiple fluid-filled cysts in their kidneys that lead to a massive enlargement of the organ and gradual worsening of its function, as well as complete failure in many cases. The lack of available treatment means patients may eventually require regular dialysis or a kidney transplant.

The Prospective Association Between Positive Psychological Well-Being And Diabetes, Julia K. Boehm, Claudia Trudel-Fitzgerald, Mika Kivimaki, Laura D. Kubzansky

Psychology Faculty Articles and Research

Objective: Positive psychological well-being has protective associations with cardiovascular outcomes, but no studies have considered its association with diabetes. This study investigated links between well-being and incident diabetes.

Methods: At study baseline (1991-1994), 7,800 middle-aged British men and women without diabetes indicated their life satisfaction, emotional vitality, and optimism. Diabetes status was determined by self-reported physician diagnosis and oral glucose tolerance test (screen detection) at baseline and through 2002-2004. Incident diabetes was defined by physician-diagnosed and screen-detected cases combined and separately. Logistic regression estimated the odds of developing diabetes controlling for relevant covariates (e.g., demographics, depressive symptoms). Models …

Is Postpartum Depression A Disease Of Modern Civilization?, Jennifer Hahn-Holbrook, Martie Haselton

Psychology Faculty Articles and Research

Access to calorie-dense foods, medicine, and other comforts has made modern humans healthier than our prehistoric ancestors in many respects. However, the epidemics of obesity, diabetes, and cardiovascular disease suggest that there are also drawbacks to modern living. Here, we address the question of whether the dramatic cultural changes that have occurred over the past century have inflated rates of postpartum depression, adding postpartum depression to the list of diseases of modern civilization. We review evidence from cross-cultural, epidemiological, and experimental studies documenting associations between postpartum depression and modern patterns of early weaning, diets deficient in essential fatty acids, low …