Digital Commons Network^™

Spatial And Temporal Organization Of The Genome: Current State And Future Aims Of The 4d Nucleome Project, Job Dekker, Frank Alber, Sarah Aufmkolk, Brian J Beliveau, Benoit G Bruneau, Andrew S Belmont, Lacramioara Bintu, Alistair Boettiger, Riccardo Calandrelli, Christine M Disteche, David M Gilbert, Thomas Gregor, Anders S Hansen, Bo Huang, Danwei Huangfu, Reza Kalhor, Christina S Leslie, Wenbo Li, Yun Li, Jian Ma, William S Noble, Peter J Park, Jennifer E Phillips-Cremins, Katherine S Pollard, Susanne M Rafelski, Bing Ren, Yijun Ruan, Yaron Shav-Tal, Yin Shen, Jay Shendure, Xiaokun Shu, Caterina Strambio-De-Castillia, Anastassiia Vertii, Huaiying Zhang, Sheng Zhong

Journal Articles

The four-dimensional nucleome (4DN) consortium studies the architecture of the genome and the nucleus in space and time. We summarize progress by the consortium and highlight the development of technologies for (1) mapping genome folding and identifying roles of nuclear components and bodies, proteins, and RNA, (2) characterizing nuclear organization with time or single-cell resolution, and (3) imaging of nuclear organization. With these tools, the consortium has provided over 2,000 public datasets. Integrative computational models based on these data are starting to reveal connections between genome structure and function. We then present a forward-looking perspective and outline current aims to …

Neurotropic Manifestations As A Potential Risk Factor For Schizophrenia Following In Utero Exposure To Sars-Cov-2, Mir Ali R Talpur, Omar H. Elsayed, Rif S. El-Mallakh

The University of Louisville Journal of Respiratory Infections

Background: COVID-19 infection is associated with neurologic and psychiatric morbidity that suggests a direct effect of the virus or secondary effect of an inflammatory process. These neuropsychiatric consequences may increase the likelihood of schizophrenia in the offspring of women who become infected with COVID-19 during their pregnancy.

Methods: We performed a directed narrative review of the literature focusing on the proposed pathophysiological processes that lead to schizophrenia and known pathological consequences of COVID-19 infection.

Results: Schizophrenia in adult offspring has been associated with maternal infections during pregnancy by a wide range of respiratory and neurotropic pathogens. Spikes in the incidence …

The Building Healthy Eating And Self-Esteem Together For University Students Mobile App To Treat Eating Disorders: User-Centered Research Design And Feasibility Study., Kelsie T. Forbush, Kara A. Christensen Pacella, Marianna L. Thomeczek, Sara R. Gould, Danielle A N Chapa, Brianne N. Richson, Victoria L. Perko, Joseph Ayres, Yiyang Chen, Sonakshi Negi

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: University students are an at-risk group for the development of eating disorders (EDs); however, many college campuses lack sufficient resources to provide ED specialty care. Students report unique reasons for not seeking ED treatment, including the desire to solve the problem on their own (eg, seeking help from friends, self-medicating, or waiting to see if their problems improve), inability to afford treatment, lack of time to participate in the treatment, fear of seeing their primary care physician, and lack of recognition of their issues as an ED. Mobile health (mHealth) apps may be a cost-effective, helpful adjunctive tool to …

The History Of Geriatric Emergency Medicine, Teresita M. Hogan Md, Lowell Gerson Phd, Aurthur B. Sanders Md

Journal of Geriatric Emergency Medicine

Abstract: Excellent emergency care does not happen by chance. The standard emergency approach that excels in the young, fails in older patients. Older adults experience unnecessary morbidity and excess mortality in our emergency departments. This article describes the pursuit of excellent emergency care in the historically challenging older adult population. A pivotal point occurred once emergency physicians recognized older patients as a distinct population in need of unique evaluation and treatment.

In the early 1990s a group of geriatricians, philanthropists, and emergency physicians joined forces to improve older patient care. Geriatric Emergency Medicine (GEM) emerged as a subspecialty as these …

Creating And Implementing A Principal Investigator Tool Kit For Enhancing Accrual To Late Phase Clinical Trials: Development And Usability Study., Kristin A Higgins, Alexandra Thomas, Nancy Soto, Rebecca Paulus, Thomas J George, Thomas B Julian, Sharon Hartson Stine, Merry Jennifer Markham, Maria Werner-Wasik

Kimmel Cancer Center Faculty Papers

BACKGROUND: Accrual to oncology clinical trials remains a challenge, particularly during the COVID-19 pandemic. For late phase clinical trials funded by the National Cancer Institute, the development of these research protocols is a resource-intensive process; however, mechanisms to optimize patient accrual after trial activation are underdeveloped across the National Clinical Trial Network (NCTN). Low patient accrual can lead to the premature closure of clinical trials and can ultimately delay the availability of new, potentially life-saving therapies in oncology.

OBJECTIVE: The purpose of this study is to formally create an easily implemented tool kit of resources for investigators of oncology clinical …

The Dangers Of Aces, Olivia Carey, Thea Forrest, Adna Abdi

MaineHealth Maine Medical Center

ACEs stands for Adverse Childhood Experiences, included (but not limited to) physical, emotional, and sexual abuse, substance abuse, neglect, dysfunctional families, and mental illness'. ACEs impacts childhood development and increases chances of future health implications.

Is Covid-19 Pushing Us To The Fifth Industrial Revolution (Society 5.0)?, Zouina Sarfraz, Azza Sarfraz, Hamza M. Iftikar, Ramsha Akhund

Department of Paediatrics and Child Health

The coronavirus disease 2019 (COVID-19) pandemic may further promote the development of Industry 4.0 leading to the fifth industrial revolution (Society 5.0). Industry 4.0 technology such as Big Data (BD) and Artificial Intelligence (AI) may lead to a personalized system of healthcare in Pakistan. The final bridge between humans and machines is Society 5.0, also known as the super-smart society that employs AI in healthcare manufacturing and logistics. In this communication, we review various Industry 4.0 and Society 5.0 technologies including robotics and AI being inspected to control the rate of transmission of COVID-19 globally. We demonstrate the applicability of …

Prolonged Environmental Enrichment Promotes Developmental Myelination., Evan Z Goldstein, Vera Pertsovskaya, Thomas A Forbes, Jeffrey L Dupree, Vittorio Gallo

Pediatrics Faculty Publications

Postnatal neurodevelopment is profoundly influenced by environmental experiences. Environmental enrichment is a commonly used experimental paradigm that has uncovered numerous examples of experience-dependent plasticity in health and disease. However, the role of environmental enrichment in normal development, especially glial development, is largely unexplored. Oligodendrocytes, the myelin-forming glia in the central nervous system, provide metabolic support to axons and establish efficient saltatory conduction by producing myelin. Indeed, alterations in myelin are strongly correlated with sensory, cognitive, and motor function. The timing of developmental myelination is uniquely positioned to be influenced by environmental stimuli, as peak myelination occurs postnatally and continues into …

Early Enteral Feeding In Preterm Infants: A Narrative Review Of The Nutritional, Metabolic, And Developmental Benefits, Melissa K. Thoene, Ann Anderson-Berry

Journal Articles: Pediatrics

Enteral feeding is the preferred method of nutrient provision for preterm infants. Though parenteral nutrition remains an alternative to provide critical nutrition after preterm delivery, the literature suggests that enteral feeding still confers significant nutritional and non-nutritional benefits. Therefore, the purpose of this narrative review is to summarize health and clinical benefits of early enteral feeding within the first month of life in preterm infants. Likewise, this review also proposes methods to improve enteral delivery in clinical care, including a proposal for decision-making of initiation and advancement of enteral feeding. An extensive literature review assessed enteral studies in preterm infants …

Manf Is Neuroprotective Against Ethanol-Induced Neurodegeneration Through Ameliorating Er Stress, Yongchao Wang, Wen Wen, Hui Li, Marco Clementino, Hong Xu, Mei Xu, Murong Ma, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are a spectrum of developmental disorders caused by prenatal alcohol exposure. Neuronal loss or neurodegeneration in the central nervous system (CNS) is one of the most devastating features in FASD. It is imperative to delineate the underlying mechanisms to facilitate the treatment of FASD. Endoplasmic reticulum (ER) stress is a hallmark and an underlying mechanism of many neurodegenerative diseases, including ethanol-induced neurodegeneration. Mesencephalic astrocyte-derived neurotrophic factor (MANF) responds to ER stress and has been identified as a protein upregulated in response to ethanol exposure during the brain development. To investigate the role of MANF in …

Screen Time Effects On Children And Adolescents In Both The United States And Australia, Marrisa Cox

Honors Projects

Technology and screen time have become an essential part of everyday life in many countries across the world. Children in Australia and the United States are exposed to increasing hours of technology exceeding recommendations by pediatricians in both countries. Pediatricians suggest limiting screen time due to the research indicating possible impact on social development, and unhealthy emotional and physical outcomes in children. The objective of this paper was to review the mental and physical impacts of screen time on young and adolescent children and to compare and contrast policies regulating screen time in the United States and Australia. The information …

Corporeal Quintessence, Jordan Lamb, Michael Cyr

Akesis

In keeping with the theme of “Historia Habitus” this collection is meant to illustrate how the physical form is a living history, with every movement written into the striations of the human musculature. The old adage “you are what you eat” is easily extended to “you are what you do”. Contemplate the hours and repetitions that have gone into sculpting the highlighted regions of our model/athletes. We hope this collection stimulates reflection on what the body can tell you about your past and what your, or perhaps your patient’s, lifestyle can predict about the future.

Exploring Infant Leukemia Through Exome Sequencing And An In Vitro Model Of Hematopoietic Development, Mark Cannon Valentine

Arts & Sciences Electronic Theses and Dissertations

Cancer is a heterogeneous disease with myriad causes and outcomes. Many of the cancers that occur in adult populations have become increasingly well characterized with the advent of affordable high-throughput sequencing. These studies have revealed that cancer is largely a disease of somatic mutation in the adult population. In strong contrast to this, childhood cancers have an exceedingly low rate of somatic mutation. At the extreme end of this spectrum is Infant Leukemia (IL). Sequencing of IL has revealed that these tumors frequently have one or fewer somatic SNP. In the absence of a somatic explanation for IL, many other …

Screening For Developmental Delays During The Well-Child Visit, Ellen Walker Seyller

Family Medicine Clerkship Student Projects

Due to recent staffing transitions, family medicine physicians at Newtown Primary Care in Danbury, CT are now managing the care of an increasing number of pediatric patients. The goal of this project was to develop a screening tool to allow practitioners to assess for developmental delays during well-child visits. The tool includes 10-question surveys for ages 1mo, 2mo, 4mo, 6mo, 12mo, 15mo, 2yo, 3yo, or 4yo with a scoring guide and a list of some concerning signs at each stage.

Rates Of Developmental And Behavioral Screening Of Young Children: Implications For Health Care Policy And Practice, Shirley Berger

Dissertations and Theses

Background: The skills and capacities developed during early childhood are the foundation for a child’s future academic functioning, economic productivity, and lifelong health and mental health. When young children have developmental delays or disabilities, early identification and intervention lead to better outcomes; however, only a minority are identified before school entry. Primary care is an important setting for identification of developmental and behavioral conditions as most young children attend well-child visits regularly and parents expect developmental guidance from pediatricians. Two key pediatric preventive services are recommended: developmental monitoring/surveillance at every well-child visit and developmental screening at 9 months, 18 months, …

Innate Lymphoid Cells: Transcriptional Profiles And Cytokine Developmental Requirements, Michelle Lauren Robinette

Arts & Sciences Electronic Theses and Dissertations

Innate lymphoid cells (ILCs) are a recently discovered lineage of professional cytokine-producing cells that strikingly mirror T cells in transcriptional circuitry and effector functions, but derive from distinct progenitors and do not express recombined antigen-specific receptors. These cells include natural killer (NK) cells, which parallel cytotoxic CD8+ T cells, and three additional classes of ILCs enriched at mucosal surfaces that generate signature cytokines reminiscent of polarized CD4+ helper T cells subsets, called ILC1, ILC2, and ILC3. As ILCs have been implicated in the pathogenesis of colitis, cancer, allergy, and autoimmunity in both human and mouse, understanding the functional capacity of …

A Model For Investigating Developmental Eye Repair In Xenopus Laevis, Cindy X. Kha, Philip H. Son, Julia Lauper, Kelly Ai-Sun Tseng

Life Sciences Faculty Research

Vertebrate eye development is complex and requires early interactions between neuroectoderm and surface ectoderm during embryogenesis. In the African clawed frog, Xenopus laevis, individual eye tissues such as the retina and lens can undergo regeneration. However, it has been reported that removal of either the specified eye field at the neurula stage or the eye during tadpole stage does not induce replacement. Here we describe a model for investigating Xenopus developmental eye repair. We found that tailbud embryos can readily regrow eyes after surgical removal of over 83% of the specified eye and lens tissues. The regrown eye reached a …

Training Neurodegenerative Disease Support Group Leaders: A New Support Group Functioning Scale, Therese V. Cash, Christopher Kilbourn, Sarah K. Lageman

Neurology Publications

Support group leaders play pivotal roles in maintaining healthy community support groups; however, these leaders also have personal support needs and typically lack formal training in managing complex behaviors of neurodegenerative disorders. A support group well-being questionnaire, assessing support group functioning, was developed and piloted among participants of an educational training program designed for support group leaders of various neurodegenerative disorder-specific support groups. An exploratory factor analysis evaluated the questionnaire’s psychometric properties and identified a reliable single factor five-item solution, which was titled the Support Group Functioning Scale (SGFS). Preliminary interpretation guidelines were proposed. Development of this scale is a …

Tissue Specific Origin, Development, And Pathological Perspectives Of Pericytes., Tomoko Yamazaki, Yoh-Suke Mukouyama

Articles, Abstracts, and Reports

Pericytes are mural cells surrounding blood vessels, adjacent to endothelial cells. Pericytes play critical roles in maturation and maintenance of vascular branching morphogenesis. In the central nervous system (CNS), pericytes are necessary for the formation and regulation of the blood-brain barrier (BBB) and pericyte deficiency accompanies CNS diseases including multiple sclerosis, diabetic retinopathy, neonatal intraventricular hemorrhage, and neurodegenerative disorders. Despite the importance of pericytes, their developmental origins and phenotypic diversity remain incompletely understood. Pericytes express multiple markers and the origin of pericytes differs by tissue, which may cause difficulty for the identification and understanding of the ontogeny of pericytes. Also, …

Bone Fracture Incidence, Measurement And Adaptation: An Exploration Through The Continuum From Incidence To Measurement And Adaptation, Mark Jenkins

Theses: Doctorates and Masters

This research encompasses four studies exploring bone adaptation, fracture incidence, and preventative measures to decrease fracture risk and increase bone health. Study one was a clinical audit exploring incidence rates for appendicular fractures in children in Western Australia over ten years. Diagnostic and remedial approaches were explored in studies two, three and four by examining the between-day reliability of upper limb scans; reliability of the osteogenic index (OI) for upper-body strength and power exercises; and the diagnostic value or utility of using pQCT in disease profiling, respectively. Fracture rates in the limbs of children were found to be increasing each …

Update On The Notochord Including Its Embryology, Molecular Development, And Pathology: A Primer For The Clinician., Tushar Ramesh, Sai V Nagula, Gabrielle G Tardieu, Erfanul Saker, Mohammadali Shoja, Marios Loukas, Rod J Oskouian, R Shane Tubbs

Articles, Abstracts, and Reports

The notochord is a rod-like embryological structure, which plays a vital role in the development of the vertebrate. Though embryological, remnants of this structure have been observed in the nucleus pulposus of the intervertebral discs of normal adults. Pathologically, these remnants can give rise to slow-growing and recurrent notochord-derived tumors called chordomas. Using standard search engines, the literature was reviewed regarding the anatomy, embryology, molecular development, and pathology of the human notochord. Clinicians who interpret imaging or treat patients with pathologies linked to the notochord should have a good working knowledge of its development and pathology.

Inhibition Of P73 Function By Pifithrin-Α As Revealed By Studies In Zebrafish Embryos, William R Davidson, Qing Ren, Gabor Kari, Ori Kashi, Adam Dicker Md, Phd, Ulrich Rodeck

Bodine Journal

The p53 family of proteins contains two members that have been implicated in sensitization of cells and organisms to genotoxic stress, i.e., p53 itself and p73. In vitro, lack of either p53 or p73 can protect certain cell types in the adult organism against death upon exposure to DNA damaging agents. The present study was designed to assess the relative contribution of p53 to radiation resistance of an emerging vertebrate model organism, i.e., zebrafish embryos. Consistent with previous reports, suppressing p53 protein expression using antisense morpholino oligonucleotides (MOs) increased survival and reduced gross morphological alterations in zebrafish embryos exposed to …

Acth Prevents Deficits In Fear Extinction Associated With Early Life Seizures, Andrew T. Massey, David K. Lerner, Gregory L. Holmes, Rod C. Scott, Amanda Hernan

Dartmouth Scholarship

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action.

Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish …

Retinoic Acid And The Development Of The Endoderm, Gregory M. Kelly, Thomas A. Drysdale

Paediatrics Publications

Retinoic acid (RA) is an important signaling molecule in the development of the endoderm and an important molecule in protocols used to generate endodermal cell types from stem cells. In this review, we describe the RA signaling pathway and its role in the patterning and specification of the extra embryonic endoderm and different endodermal organs. The formation of endoderm is an ancient evolutionary feature and RA signaling appears to have coevolved with the vertebrate lineage. Towards that end, we describe how RA participates in many regulatory networks required for the formation of extraembryonic structures as well as the organs of …

Hypothyroidism And The Development Of Hypertension, Kaleb Short

All Graduate Theses, Dissertations, and Other Capstone Projects

Low thyroid hormone (TH) in adulthood is associated with increased risk of cardiovascular disease, including risk of hypertension. The Spontaneously Hypertensive Rat (SHR), exhibits alterations in thyroid function when compared to normotensive controls. Interestingly, inhibiting thyroid gland function before 4 weeks of age prevented hypertension in the SHR, indicating that TH is involved in the etiology of SHR hypertension. However, these studies utilized tail-cuff photoplethysmography (PPG), which is known to have stress-induced artifacts, and did not compare effects in the normotensive parent strain Wistar Kyoto (WKY) rat. Therefore, it is uncertain whether TH is responsible for an elevation in baseline …

Cochlear Development And Auditory Function In The Absence Of Thyroid Hormone Transporters Mct8 And Oatp1c1, Richard Sinn

All Graduate Theses, Dissertations, and Other Capstone Projects

Thyroid hormone (TH) is essential for the development and maturation of the nervous system. The thyroid gland secretes an active form of TH, triiodothyronine, and a prohormone, thyroxine, into the blood. TH is charged, which prevents it from passively diffusing across cell membranes and thus requires cell membrane transporters to facilitate its movement into and out of cells. However, whether TH transporters are required for TH-mediated developmental events, including the auditory system, is largely unknown.

The purpose of the present study was to investigate two specific TH transporters, monocarboxylate transporter 8 (Mct8) and organic anion transporting polypeptide 1c1 (Oatp1c1), and …

Withanolide Compounds As Inhibitors Of Fibrosis And Identification Of Molecular Targets For Anti-Fibrotic Drug Development, Royce Mohan, Paola Bargagna-Mohan

Ophthalmology and Visual Science Faculty Patents

Provided are methods for screening for drugs effective for treating fibrotic conditions. One screening method comprises exposing a cell to a test compound, monitoring the effect of the test compound on the amount or form of a cell molecule, comparing the amount or form of the cell molecule with the result obtained by treatment of the cell with an anti-fibrotic -effective amount of a withanolide compound, and selecting a drug effective for treating a fibrotic disease based on the ability of the test compound to provide the effect obtained by the withanolide compound on the cell molecule. Also provided is …

Primary School Vision Screening Involving Teachers In Nampula, Mozambique, Aoife Phelan, Lisa O'Donoghue, Kathryn Saunders, Stephen Thompson, Vivien Ocampo, Kevin Naidoo, James Loughman

Conference Papers

Purpose: There is no plan for a national child eye care programme or existing human resource infrastructure to address the immediate challenge of child eye health in Mozambique.This study aims to design, implement and evaluate a school based pediatric vision screening service, to identify those in need of eye care services, among Mozambique’s 11,561,000 children.

Methods: Primary School Screening took place in three schools in Nampula, Mozambique in September 2010 and March 2011. The children’s vision was screened by an optometry student, optometrist or teacher with Log MAR ETDRS letters at 4 Meters. Ophthalmoscopy was performed on all children by …

Prenatal Maternal Stress Programs Infant Stress Regulation, Elyssia Poggi Davis, Laura M. Glynn, Feizal Waffarn, Curt A. Sandman

Psychology Faculty Articles and Research

Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.

Methods: The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36 + weeks' gestational age. Infant cortisol and behavioral responses to the painful stress of a heel-stick blood draw were evaluated at 24 hours after …

Como Mujer…Yo Decido: El Derecho De Salud Sexual Y Reproductiva En Mujeres Aymara De Putre, Chile, Alice Manos

Independent Study Project (ISP) Collection

The human right to sexual and reproductive health, as defined at the International United Nations Conference on Population and Development (Cairo, 1994), continues to be a pending issue in Chile. The sexual and reproductive health of indigenous women emerges as a crucial issue within this field due to Chile’s history of cultural ignorance and a dictatorial healthcare system. Studies of women’s sexual and reproductive healthcare within indigenous communities in Chile have focused on the Cosmo vision and traditional medicine of the Aymara due to their distinct concepts of reproduction, gender roles, and family planning. Studies conducted by Maria Soledad Pérez …