Medicine and Health Sciences Commons^™

Expression Of Phosphodiesterase 6 (Pde6) In Human Breast Cancer Cells, Hongli Dong, Kevin P. Claffey, Stefan Brocke, Paul M. Epstein

UCHC Articles - Research

Considerable epidemiological evidence demonstrates a positive association between artificial light at night (LAN) levels and incidence rates of breast cancer, suggesting that exposure to LAN is a risk factor for breast cancer. There is a 30-50% higher risk of breast cancer in the highest LAN exposed countries compared to the lowest LAN countries, and studies showing higher incidence of breast cancer among shift workers exposed to more LAN have led the International Agency for Research on Cancer to classify shift work as a probable human carcinogen. Nevertheless, the means by which light can affect breast cancer is still unknown. In …

Reproducibility Of Ambulatory Blood Pressure Changes From The Initial Values On Two Different Days, Garrett I. Ash

Open Access Author Fund Awardees' Articles

OBJECTIVE: We tested the reproducibility of changes in the ambulatory blood pressure (BP) from the initial values, an indicator of BP reactivity and cardiovascular health outcomes, in young, healthy adults. METHOD: The subjects wore an ambulatory BP monitor attached by the same investigator at the same time of day until the next morning on two different days (day 1 and day 2) separated by a week. We compared the ambulatory BP change from the initial values at hourly intervals over 24 waking and sleeping hours on days 1 and 2 using linear regression and repeated measures analysis of covariance. RESULTS: …

Highlights From The Functional Single Nucleotide Polymorphisms Associated With Human Muscle Size And Strength Or Famuss Study, Linda S. Pescatello, Paul D. Thompson

Open Access Author Fund Awardees' Articles

The purpose of the Functional Single Nucleotide Polymorphisms Associated with Human Muscle Size and Strength study or FAMuSS was to identify genetic factors that dictated the response of health-related fitness phenotypes to resistance exercise training (RT). The phenotypes examined were baseline muscle strength and muscle, fat, and bone volume and their response to RT. FAMuSS participants were 1300 young (24 years), healthy men (42%) and women (58%) that were primarily of European-American descent. They were genotyped for ~500 polymorphisms and completed the Paffenbarger Physical Activity Questionnaire to assess energy expenditure and time spent in light, moderate, and vigorous intensity habitual …

One-Day Treatment Of Small Molecule 8-Bromo-Cyclic Amp Analogue Induces Cell-Based Vegf Production For In Vitro Angiogenesis And Osteoblastic Differentiation, Kevin W.-H. Lo, Ho Man Kan, Keith A. Gagnon, Cato T. Laurencin

UCHC Articles - Research

Small molecule based regenerative engineering is emerging as a promising strategy for regenerating bone tissue. Small molecule cAMP analogues have been proposed as novel biofactors for bone repair and regeneration, and while promising, the effect that these small molecules have on angiogenesis, a critical requirement for successful bone regeneration, is still unclear. Our previous research demonstrated that the small molecule cAMP analogue 8-bromoadenosine-3’,5’-cyclic monophosphate (8-Br-cAMP) was able to promote initial osteoblast adhesion on a polymeric scaffold via cAMP signaling cascades. Here, we report that 8-Br-cAMP is capable of inducing in vitro cell-based VEGF production for angiogenesis promotion. We first demonstrated …

Microglial Responses After Ischemic Stroke And Intracerebral Hemorrhage, Roslyn A. Taylor, Lauren H. Sansing

UCHC Articles - Research

Stroke is a leading cause of death worldwide. Ischemic stroke is caused by blockage of blood vessels in the brain leading to tissue death, while intracerebral hemorrhage (ICH) occurs when a blood vessel ruptures, exposing the brain to blood components. Both are associated with glial toxicity and neuroinflammation. Microglia, as the resident immune cells of the central nervous system (CNS), continually sample the environment for signs of injury and infection. Under homeostatic conditions, they have a ramified morphology and phagocytose debris. After stroke, microglia become activated, obtain an amoeboid morphology, and release inflammatory cytokines (the M1 phenotype). However, microglia can …

Healthnet News V.28:No.3 Fall 2013, Judith S. Kronick, Alberta Richetelle

Articles - Patient Care

A newsletter for public librarians and others interested in consumer health information services.

Examining A Ripple Effect: Do Spouses’ Behavior Changes Predict Each Other’S Weight Loss?, Anna E. Schierberl-Scherr, Amy A. Gorin

Open Access Author Fund Awardees' Articles

Background. Including spouses in obesity treatment has been found to promote weight loss. We assessed whether spouses’ diet and activity changes impacted each other’s weight loss when both members attended an active weight loss program (TOGETHER) or only the primary participant attended treatment (ALONE).

Methods. Heterosexual couples (𝑁 = 132) enrolled in an 18-month randomized controlledweight loss trialwereweighed and completedmeasures of dietary intake and physical activity at baseline and 6 months. We conducted dyadic data analyses using the Actor-Partner Interdependence Model.

Results. Participants’ weight loss was not predicted by their partners’ behavior changes.However, partners’ weight loss was predicted by …

Semi-Automated Curation Of Metabolic Models Via Flux Balance Analysis: A Case Study With Mycoplasma Gallisepticum, Eddy J. Bautista, Joseph Zinski, Steven M. Szczepanek, Erik L. Johnson, Edan R. Tulman, Steven J. Geary, Ranjan Srivastava

Open Access Author Fund Awardees' Articles

Primarily used for metabolic engineering and synthetic biology, genome-scale metabolic modeling shows tremendous potential as a tool for fundamental research and curation of metabolism. Through a novel integration of flux balance analysis and genetic algorithms, a strategy to curate metabolic networks and facilitate identification of metabolic pathways that may not be directly inferable solely from genome annotation was developed. Specifically, metabolites involved in unknown reactions can be determined, and potentially erroneous pathways can be identified. The procedure developed allows for new fundamental insight into metabolism, as well as acting as a semi-automated curation methodology for genome-scale metabolic modeling. To validate …

Preosteocytes/Osteocytes Have The Potential To Dedifferentiate Becoming A Source Of Osteoblasts, Elena Torreggiani, Brya G. Matthews, Slavica Pejda, Igor Matic, Danka Grcevic, Mark C. Horowitz, Ivo Kalajzic

UCHC Articles - Research

Presently there is no clear evidence for the ability of mature osteogenic lineage cells to dedifferentiate. In order to identify and trace mature osteogenic lineage cells, we have utilized transgenic mouse models in which the dentin matrix protein 1 (Dmp1) promoter drives expression of GFP (active marker) or Cre recombinase (historic label) in preosteocytes/osteocytes. In long bone chip outgrowth cultures, in which cells on the bone surface were enzymatically removed, cells with previous activity of the Dmp1 promoter migrated onto plastic and down-regulated Dmp1-GFP expression. Dmp1Cre-labeled cells from these cultures had the potential to re-differentiate into the osteogenic lineage, while …

The Effect Of Robot-Child Interactions On Social Attention And Verbalization Patterns Of Typically Developing Children And Children With Autism Between 4 And 8 Years, Sudha Srinivasan, Anjana Bhat

Open Access Author Fund Awardees' Articles

Background: There is anecdotal evidence for the use of robots to facilitate prosocial behaviors such as joint attention and verbalization in children with Autism Spectrum Disorders (ASDs). However, there have been no normative data in typically developing children to evaluate the effects of robot-child interactions on social and communication skills. Objectives: The aim of our study was to evaluate the changes in social attention and verbalization skills of 15 typically developing (TD) children, using a structured 8-session imitation protocol within a robot-adult-child context. We further extended this imitation protocol to two children with ASDs. Methods: Pretest, session1, session 4, session …

Can Stem Cells Be Used To Generate New Lungs? Ex Vivo Lung Bioengineering With Decellularized Whole Lung Scaffolds, Todd J. Jensen, Eric D. Girard, Christine M. Finck

UCHC Articles - Research

For patients with end-stage lung diseases, lung transplantation is the only available therapeutic option. However, the number of suitable donor lungs is insufficient and lung transplants are complicated by significant graft failure and complications of immunosuppressive regimens. An alternative to classic organ replacement is desperately needed. Engineering of bioartificial organs using either natural or synthetic scaffolds is an exciting new potential option for generation of functional pulmonary tissue for human clinical application. Natural organ scaffolds can be generated by decellularization of native tissues; these acellular scaffolds retain the native organ ultrastructure and can be seeded with autologous cells toward the …

Osterix-Cre Labeled Progenitor Cells Contribute To The Formation And Maintenance Of The Bone Marrow Stroma, Yaling Liu, Sara Strecker, Liping Wang, Mark S. Kronenberg, Wen Wang, David W. Rowe, Peter F. Maye

UCHC Articles - Research

We have carried out fate mapping studies using Osterix-EGFPCre and Osterix-CreERt animal models and found Cre reporter expression in many different cell types that make up the bone marrow stroma. Constitutive fate mapping resulted in the labeling of different cellular components located throughout the bone marrow, whereas temporal fate mapping at E14.5 resulted in the labeling of cells within a region of the bone marrow. The identity of cell types marked by constitutive and temporal fate mapping included osteoblasts, adipocytes, vascular smooth muscle, perineural, and stromal cells. Prolonged tracing of embryonic precursors labeled at E14.5dpc revealed the continued …

Utilization Of Transgenic Models In Evaluation Of Osteogenic Differentiation Of Embryonic Stem Cells, Dario Repic, Elena Torreggiani, Tiziana Franceschetti, Brya G. Matthews, Alexander C. Lichtler, Ivo Kalajzic

UCHC Articles - Research

Previous studies reported that embryonic stem cells (ESCs) can be induced to differentiate into cells showing a mature osteoblastic phenotype by culturing them under osteo-inductive conditions. It is probable that osteogenic differentiation requires that ESCs undergo differentiation through an intermediary step involving a mesenchymal lineage precursor. Based on our previous studies indicating that adult mesenchymal progenitor cells express αSMA, we have generated ESCs from transgenic mice in which an αSMA promoter directs the expression of red fluorescent protein (RFP) to mesenchymal progenitor cells. To track the transition of ESC-derived MSCs into mature osteoblasts, we have utilized a bone-specific fragment of …

The Effects Of Estrogen In Ischemic Stroke, Louise D. Mccullough, Edward C. Koellhoffer

UCHC Articles - Research

Stroke is a leading cause of death and the most common cause of long-term disability in the USA. Women have a lower incidence of stroke compared with men throughout most of the lifespan which has been ascribed to protective effects of gonadal steroids, most notably estrogen. Due to the lower stroke incidence observed in pre-menopausal women and robust preclinical evidence of neuroprotective and anti-inflammatory properties of estrogen, researchers have focused on the potential benefits of hormones to reduce ischemic brain injury. However, as women age, they are disproportionately affected by stroke, coincident with the loss of estrogen with menopause. The …

Knockout Of Vascular Early Response Gene Worsens Chronic Stroke Outcomes In Neonatal Mice, Mehwish A. Mirza, Lori A. Capozzi, Yan Xu, Louise D. Mccullough, Fudong Liu

UCHC Articles - Research

Vascular early response gene (Verge) is a novel immediate early gene that is highly expressed during developmental angiogenesis and after ischemic insults in adult brain. However, the role of Verge after neonatal injury is not known. In the present study, we investigated the hypothesis that Verge contributes to vascular remodeling and tissue repair after neonatal ischemic injury. The Rice–Vanucci model (RVM) was employed to induce neonatal stroke in both Verge knockout (KO) and wild-type (WT) postnatal day 10 (P10) mice. Histological and behavioral outcomes at acute (24 h), subacute (7 days) and chronic (30 days) phases were evaluated. Angiogenesis, neurogenesis, …

Transgenic Sickle Cell Disease Mice Have High Mortality And Dysregulated Immune Responses After Vaccination, Steven M. Szczepanek, Eric R. Secor Jr, Sonali J. Bracken, Linda Guernsey, Ektor Rafti, Adam Matson, Roger S. Thrall

UCHC Articles - Research

Background

Children with sickle cell disease (SCD) are susceptible to recurrent infections, which are often life threatening and necessitate frequent vaccinations. Given the altered baseline immunity and proinflammatory state associated with SCD, we sought to determine the relative safety and efficacy of vaccination in transgenic SCD mice.

Methods

Eight week-old SCD mice were vaccinated with ovalbumin (OVA) and aluminum hydroxide weekly for three weeks by the intraperitoneal (IP) or intramuscular (IM) route. One week after the third vaccination, serum cytokines/chemokines, immunoglobulins, and bronchoalveolar lavage (BAL) fluid cytokines were measured.

Results

Only SCD mice were prone to mortality associated with vaccination …

Ptpn11 Deletion In A Novel Cartilage Cell Causes Metachondromatosis By Activating Hedgehog Signaling, Qian Wu

UCHC Articles - Research

SHP2, encoded by PTPN11, is required for survival, proliferation and differentiation of various cell types^1,2. Germ line activating mutations in PTPN11 cause Noonan Syndrome, while somatic PTPN11 mutations cause childhood myeloproliferative disease and contribute to some solid tumors. Recently, heterozygous inactivating mutations in PTPN11 were found in metachondromatosis, a rare inherited disorder featuring multiple exostoses, endochondromas, joint destruction and bony deformities^3,4. The detailed pathogenesis of this disorder has remained unclear. Here, we used a conditional knockout allele (Ptpn11^fl) and Cre recombinase (Cre) transgenic mice to delete Ptpn11 specifically in …

Healthnet News V.28:No.2 Summer 2013, Judith S. Kronick, Alberta Richetelle

Articles - Patient Care

A newsletter for public librarians and others interested in consumer health information services.

The Transcriptomics To Proteomics Of Hair Cell Regeneration: Looking For A Hair Cell In A Haystack, Gopinath Rajadinakaran

UCHC Articles - Research

Mature mammals exhibit very limited capacity for regeneration of auditory hair cells, while all non-mammalian vertebrates examined can regenerate them. In an effort to find therapeutic targets for deafness and balance disorders, scientists have examined gene expression patterns in auditory tissues under different developmental and experimental conditions. Microarray technology has allowed the large-scale study of gene expression profiles (transcriptomics) at whole-genome levels, but since mRNA expression does not necessarily correlate with protein expression, other methods, such as microRNA analysis and proteomics, are needed to better understand the process of hair cell regeneration. These technologies and some of the results of …

Novel Space Alters Theta And Gamma Synchrony Across The Longitudinal Axis Of The Hippocampus., Stephanie C. Penley, James R. Hinman, Lauren L. Long, Etan J. Markus, Monty A. Escabí, James J. Chrobak

Open Access Author Fund Awardees' Articles

Hippocampal theta (6–10 Hz) and gamma (25–50 Hz and 65–100 Hz) local field potentials (LFPs) reflect the dynamic synchronization evoked by inputs impinging upon hippocampal neurons. Novel experience is known to engage hippocampal physiology and promote successful encoding. Does novelty synchronize or desynchronize theta and/or gamma frequency inputs across the septotemporal (long) axis of the hippocampus (HPC)? The present study tested the hypothesis that a novel spatial environment would alter theta power and coherence across the long axis. We compared theta and gamma LFP signals at individual (power) and millimeter distant electrode pairs (coherence) within the dentate gyrus (DG) and …

Subtelomeric Hotspots Of Aberrant 5-Hydroxymethylcytosine-Mediated Epigenetic Modifications During Reprogramming To Pluripotency, Stormy J. Chamberlain, I-Ping Chen

UCHC Articles - Research

Mammalian somatic cells can be directly reprogrammed into induced pluripotent stem cells (iPSCs) by introducing defined sets of transcription factors. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem cells (ESCs). Human ES cells contain 5-hydroxymethylcytosine (5hmC), which is generated through the oxidation of 5-methylcytosine by the TET enzyme family. Here we show that 5hmC levels increase significantly during reprogramming to human iPSCs mainly due to TET1 activation, and this hydroxymethylation change is critical for optimal epigenetic reprogramming, but does not compromise primed pluripotency. Compared with hES cells, we find iPS cells tend to form …

Self-Medication Practices Of Adults With Sickle Cell Disease: Design And Methodology, Courtney Marie Beyers

Honors Scholar Theses

Aim of study

To survey the self-medication practices of adults with Sickle Cell Disease (SCD) using NIH-validated ActualMeds™ Medication Management System via Apple iPad®, in order to improve individual medication management (adherence).

Rationale and Significance

Adults with SCD are a significant population to study when considering self-medication behaviors. Because individuals with SCD are now outgrowing the speciality care of pediatricians, and often find themselves left to manage multiple medications and self-care interventions.

This research is important in understanding medication management, such as high-risk medication adherence behaviors, prescription drug interactions, and over-the-counter drug interactions with prescription drugs in the UCHC patient …

Self-Medication Practices Of Undergraduate College Students: Non-Medical Prescriptive Stimulant Use, Kim M. Vo

Honors Scholar Theses

Purpose: The purpose of this study was to determine self-medication practices of undergraduate students enrolled at the University of Connecticut in attempt to inform future educational efforts on drug misconceptions in order to encourage safe medication practices among incoming undergraduate students.

Background: Non-medical use of stimulants prescribed for attention-deficit/hyperactivity disorder (ADHD) treatment has gained attention due to non-medical prevalence rates in U.S. colleges. Current literature investigates circumstances, demographics and motives in sample populations that increase student misuse of these prescription medications.

Methods:

Design: Multi-method research strategy investigating the perceived focus group coded data to the actual self-reported Adhere Tx Know …

Limited English Proficient Patient's Use Of Family Members And Interpreters: A Pilot Study, Brittany T. Histing

Honors Scholar Theses

The purpose of this study is to explore and describe the experiences of “Spanish speaking, Spanish dominant and Limited English Proficient Latino patients” accessing health care in the United States (Parés-Avila, Sobralske, & Katz). This will be a descriptive study addressing caring for LEP patients accessing the healthcare setting using interpreters. The goal of the study is to describe LEP patient’s familiarity of interpreter services available via the CLAS standards, describe LEP patient’s experiences accessing healthcare in the United States, and describe LEP patient’s experiences in the United States health care system using or not using an interpreter.

Defining Late Onset Occult Asymptomatic Cardiotoxicity In Childhood Cancer Survivors Exposed To Anthracycline Therapy: A Cardiac Magnetic Resonance Imaging Study, Olga H. Toro-Salazar, Michael O'Loughlin, Georgine Burke, Eileen Gillan, Bruce T. Liang, Michael Taylor

Presentations - Patient Care

There are over 270,000 childhood cancer survivors in the US. Of these survivors, more than 50% have been treated with anthracyclines and are at risk of developing progressive cardiotoxicity. Novel cardiac magnetic resonance imaging (CMRI) techniques are now able to reliably detect diffuse myocardial fibrosis and changes in regional myocardial function. We hypothesized that these novel CMRI techniques will identify occult asymptomatic cardiotoxicity in a cohort of childhood cancer survivors with normal global systolic function.

In this study we demonstrate that changes in T1 mapping-derived relaxation time and left ventricular myocardial peak circumference strain are present in asymptomatic post-chemotherapy childhood …

Mmp-3 Mediates Psychosine-Induced Globoid Cell Formation: Implications For Leukodystrophy Pathology, Kumiko Ijichi, Graham D. Brown, Craig S. Moore, Paige N. Winokur, Roberto Pagarigan, Stephen J. Crocker

UCHC Articles - Research

Globoid cell leukodystrophy (GLD) or Krabbe disease, is a fatal demyelinating disease attributed to mutations in the galactocerebrosidase (GALC) gene. Loss of function mutations in GALC result in accumulation of the glycolipid intermediate, galactosylsphingosine (psychosine). Due to the cytotoxicity of psychosine, it has been hypothesized that accumulated psychosine underlie the pathophysiology of GLD. However, the cellular mechanisms of GLD pathophysiology remain unclear. Globoid cells, multinucleated microglia/macrophages in the central nervous system (CNS), are a defining characteristic of GLD. Here we report that exposure of primary glial cultures to psychosine induces the expression and the production of matrix metalloproteinase …

In Vitro Characterization Of Avian Influenza Virus Isolates With A Truncated Ns1 Gene Segment, Aaron Dick

Honors Scholar Theses

Avian Influenza Virus represents a significant threat to the world poultry population, and is a potential threat to humans due to the possibility of cross-species AIV infection. Our approach is to characterize a number of avian virus populations with respect to their content of biologically active particles that include hemagglutinating particles (HAP), plaque forming particles (PFP), interferon inducing particles (IFP), interferon induction-suppressing particles (ISP), defective-interfering particles (DIP), cell-killing particles (CKP) and non-infectious cell killing particles (niCKP) using unique in vitro assays developed for avian influenza virus in the Marcus-Sekellick Laboratory. Specifically, we will use a strain of Avian influenza virus, …

Restoring Effort-Related Functions In Models Of Depression Symptoms: Reversing Fatigue Symptoms Induced By Catecholamine Depleting Agent Tetrabenazine With The Adenosine A2a Antagonist Msx-3, Charlotte Freeland

Honors Scholar Theses

Motivational symptoms related to effort expenditure have been associated with major depression and other disorders that afflict millions of individuals worldwide. In an effort to identify potential therapeutic agents and characterize the underlying biochemical mechanisms related to these behaviors, recent research has utilized animal models to study and characterize such behavior. Previous work in the Salamone lab produced evidence that rats with impaired dopamine (DA) transmission show changes in response allocation in tasks that measure effort-related choice behavior, which are characterized by a decrease in selection of the high-effort choice but increased selection of the low-effort alternative. The present work …

Anxiety Symptoms In Individuals With High Functioning Autism, Jane C. Kelleher

Honors Scholar Theses

Research indicates a complicated relationship between anxiety disorders and autism spectrum disorders (ASDs). The current study examined the relationship between anxiety symptoms and ASD in 30 Optimal Outcome (OO) individuals, 33 High Functioning Autism (HFA) individuals, and 34 Typically Developing (TD) individuals. The groups were compared on the K-SADS measure of anxiety symptoms. The HFA group presented greater anxiety than both the OO and TD groups, and the OO and TD groups only differed on one anxiety symptom. Across all three groups, there was a significant association between greater anxiety symptoms and a higher level of social and communicative impairment. …

A Review Of “Music And Movement” Therapies For Children With Autism: Embodied Interventions For Multisystem Development, Sudha M. Srinivasan, Anjana N. Bhat

Open Access Author Fund Awardees' Articles

The rising incidence of Autism Spectrum Disorders (ASDs) has led to a surge in the number of children needing autism interventions. This paper is a call to clinicians to diversify autism interventions and to promote the use of embodied music-based approaches to facilitate multisystem development. Approximately 12% of all autism interventions and 45% of all alternative treatment strategies in schools involve music-based activities. Musical training impacts various forms of development including communication, social-emotional, and motor development in children with ASDs and other developmental disorders as well as typically developing children. In this review, we will highlight the multisystem impairments of …