Medicine and Health Sciences Commons^™

Comprehensive Management Of Presbycusis: Central And Peripheral, Kourosh Parham

Articles - Patient Care

The prevailing otolaryngologic approach to treatment of age-related hearing loss (ARHL), presbycusis, emphasizes compensation of peripheral functional deficits (i.e., hearing aids and cochlear implants). This approach does not address adequately the needs of the geriatric population, one in five of whom is expected to consist of the “old old” in the coming decades. Aging affects both the peripheral and central auditory systems, and disorders of executive function become more prevalent with advancing age. Growing evidence supports an association between age-related hearing loss and cognitive decline. Thus, to facilitate optimal functional capacity in our geriatric patients, a more comprehensive management strategy …

Racial And Ethnic Disparities In Diabetes Complications In The Northeastern United States: The Role Of Socioeconomic Status, Julie A. Wagner

UCHC Articles - Research

The role of socioeconomic status (SES) in explaining racial/ethnic disparities in diabetes remains unclear. We investigated disparities in self-reported diabetes complications, and the role of macro (e.g., income, education) and micro (e.g., ‘owning a home’ or ‘having a checking account’) SES indicators in explaining these differences. The sample included individuals with a diagnosis of diabetes (N=795) who were on average 55 years old, and 55.6% non-Hispanic White, 25.0% African American, and 19.4% Hispanic. Approximately 8% reported nephropathy, 35% reported retinopathy, and 16% reported cardiovascular disease. There were significant disparities in the rates of complications among non-Hispanic White, African American and …

The Sh2 Domain Interaction Landscape, Kazuya Machida, Christopher M. Thompson, Bruce J. Mayer

UCHC Articles - Research

Members of the SH2 domain family modulate signal transduction by binding to short peptides containing phosphorylated tyrosines. Each domain displays a distinct preference for the sequence context of the phosphorylated residue. We have developed a new high-density peptide chip technology that allows probing the affinity of most SH2 domains for a large fraction of the entire complement of tyrosine phosphopeptides in the human proteome. Using this technique we have experimentally identified thousands of putative SH2- peptide interactions for more than 70 different SH2 domains. By integrating this rich data set with orthogonal context-specific information, we have assembled an SH2 mediated …

Computationally Designed Peptide Inhibitors Against The Ubiquitin E3 Ligase Scf Fbx4, Bing Hao

UCHC Articles - Research

Telomerase is a reverse transcriptase that maintains telomere length. Telomerase activity is suppressed in somatic cells such that telomere attrition triggers replicative senescence or apop-tosis. In cancer cells, telomerase is up-regulated or reactivated, effectively making the cell immortal. Previous studies have shown that telomerase activity positively correlates with unfavorable cancer prognosis. Since it was discovered that activation of telomerase is a rate-limiting step in carcinogenesis, telomerase has gained much interest as a drug target. Both screening and structure-based methods have been extensively employed to identify small molecule leads that can selectively disrupt telomerase activity. Strategies commonly used to target telomerase …

Healthnet News V.28:No.1 Spring 2013, Judith S. Kronick, Alberta Richetelle

Articles - Patient Care

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

Case Report And Review Of Esophageal Lichen Planus Treated With Fluticasone, Marie Lourdes Ynson, Faripour Forouhar, Haleh Vaziri

Articles - Patient Care

Lichen planus is a fairly common chronic idiopathic disorder of the skin, nails and mucosal surfaces. Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in literature. Given its rarity, it can be difficult to diagnose and may be easily misdiagnosed as reflux esophagitis. Currently, there are no clear recommendations on the optimal management of this disease and little is known about the best treatment approach. Systemic steroids are usually the first line treatment and offer a favorable response. In this report, we would like to present a novel approach …

A Potential New Pathway For Pd-L1 Costimulation Of The Cd8-T Cell Response To Listeria Monocytogenes Infection, Daqi Xu, Han-Hsuan Fu, Joshua J. Obar, Leo Lefrançois

UCHC Articles - Research

Programmed death ligand-1 (PD-L1) is an important negative regulator of T cell immune responses via interactions with PD-1 and CD80. However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor is not known. We analyzed the role of PD-L1 in CD8-T cell responses to infection with Listeria monocytogenes (LM) or vesicular stomatitis virus (VSV). PD-L1 blockade impaired antigen-specific CD8 effector T cell expansion in response to LM, but not to VSV infection, particularly limiting short-lived effector cell differentiation. Simultaneous CD4-T cell depletion and anti-PD-L1 blockade revealed that PD-L1 provided costimulation even in the absence of CD4-T cells. …

Resistive-Pulse Measurements With Nanopipettes: Detection Of Au Nanoparticles And Nanoparticle-Bound Anti-Peanut Igy†, Vigneshwaran Mani, Naimish Sardesai, James F. Rusling

UCHC Articles - Research

Solid-state nanopores have been widely employed in sensing applications from Coulter counters to DNA sequencing devices. The analytical signal in such experiments is the change in ionic current flowing through the orifice caused by the large molecule or nanoparticle translocation through the pore. Conceptually similar nanopipette-based sensors can offer several advantages including the ease of fabrication and small physical size essential for local measurements and experiments in small spaces. This paper describes the first evaluation of nanopipettes with well characterized geometry for resistive-pulse sensing of Au nanoparticles (AuNP), nanoparticles coated with an allergen epitope peptide layer, and AuNP–peptide particles with …

Transient Receptor Potential (Trp) Channels And Cardiac Fibrosis, Zhichao Yue, Yanhui Zhang, Jia Xie, Jianmin Jiang, Lixia Yue

UCHC Articles - Research

Cardiac fibrosis is associated with most cardiac diseases. Fibrosis is an accumulation of excessive extracellular matrix proteins (ECM) synthesized by cardiac fibroblasts and myofibroblasts. Fibroblasts are the most prevalent cell type in the heart, comprising 75% of cardiac cells. Myofibroblasts are hardly present in healthy normal heart tissue, but appear abundantly in diseased hearts. Cardiac fibroblasts are activated by a variety of pathological stimuli, such as myocardial injury, oxidative stress, mechanical stretch, and elevated autocrine-paracrine mediators, thereby undergoing proliferation, differentiation to myofibroblasts, and production of various cytokines and ECM proteins. A number of signaling pathways and bioactive molecules are involved …

Predictors Of Adherence To Home Rehabilitation Exercises Following Anterior Cruciate Ligament Reconstruction, Howard A. Tennen

UCHC Articles - Research

Purpose/Objective

Although home exercises are commonly prescribed following anterior cruciate ligament (ACL) reconstruction and are considered important in obtaining successful rehabilitation outcomes, little is known about factors associated with the completion of such exercises. Consequently, this study was designed to identify predictors of adherence to home rehabilitation exercises after ACL surgery.

Research Method/Design

Participants (33 women, 58 men) completed indices of athletic identity, neuroticism, optimism, and pessimism before ACL surgery and measures of daily pain, negative mood, stress, and home exercise completion for 42 days postoperatively.

Results

Participants reported a high level of adherence to the prescribed regimen. Home exercise …

Membrane Association Via An N-Terminal Amphipathic Helix Is Required For The Cellular Organization And Function Of Rnase Ii, Feng Lu, Aziz Taghbalout

UCHC Articles - Research

The subcellular localization of the exoribonuclease RNase II is not known despite the advanced biochemical characterization of the enzyme. Here we report that RNase II is organized into cellular structures that appear to coil around the Escherichia coli cell periphery and that RNase II is associated with the cytoplasmic membrane by its aminoterminal amphipathic helix. The helix also acts as an autonomous transplantable membranebinding domain capable of directing normally cytoplasmic proteins to the membrane. Assembly of the organized cellular structures of RNase II required the RNase II amphipathic membrane-binding domain. Coimmunoprecipitation of the protein from cell extracts indicated that RNase …

Preconditioning Induces Sustained Neuroprotection By Down Regulation Of Ampk, Louise D. Mccullough, Venugopal Reddy Venna, Jun Li, Sharon E. Benashski, Sami Tarabishy

UCHC Articles - Research

Abstract Background and Purpose—Ischemic preconditioning (IPC) induces endogenous neuroprotection from a subsequent ischemic injury. IPC involves down-regulation of metabolic pathways. As Adenosine 5′-monophosphate-activated protein kinase (AMPK) is a critical sensor of energy balance and plays a major role in cellular metabolism, its role in IPC was investigated.

Methods—A brief 3 minute middle cerebral artery occlusion (MCAO) was employed to induce IPC in male mice 72 hours prior to 90 minute MCAO. Levels of AMPK and pAMPK, the active form of the kinase, were assessed after IPC. A pharmacological activator or inhibitor of AMPK was utilized to determine the …

Computational Analysis Of Rho Gtpase Cycling, Cibele Vieira Falkenberg, Leslie M. Loew

UCHC Articles - Research

The Rho family of GTPases control actin organization during diverse cellular responses (migration, cytokinesis and endocytosis). Although the primary members of this family (RhoA, Rac and Cdc42) have different downstream effects on actin remodeling, the basic mechanism involves targeting to the plasma membrane and activation by GTP binding. Our hypothesis is that the details of GTPase cycling between membrane and cytosol are key to the differential upstream regulation of these biochemical switches. Accordingly, we developed a modeling framework to analyze experimental data for these systems. This analysis can reveal details of GDI-mediated cycling and help distinguish between GDI-dependent and -independent …

Connecticut Guidelines For A Clinical Diagnosis Of Autism Spectrum Disorder, University Of Connecticut School Of Medicine And Dentistry

Articles - Patient Care

Overall, the number of children who are diagnosed with autism spectrum disorders (ASD) has increased. The Centers for Disease Control (CDC; CDC, 2012a) now estimates that 1 in 88 children have ASD (1 in 54 boys and 1 in 252 girls). This represents a 23% increase from data collected two years previously (CDC, 2009). This increased prevalence suggests that there is a growing need for screening and further referral, when indicated, for a diagnostic evaluation for children suspected of having ASD. To receive appropriate diagnostic services, a child must be able to obtain a comprehensive evaluation conducted by competent and …

Healthnet News V.28:No.4 Winter 2013, Judith S. Kronick, Alberta Richetelle

Articles - Patient Care

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

Coordinated Activation Of The Rac-Gap Β2-Chimaerin By An Atypical Proline-Rich Domain And Diacylglcercol, Bruce J. Mayer

UCHC Articles - Research

Chimaerins, a family of GTPase activating proteins (GAPs) for the small G-protein Rac, have been implicated in development, neuritogenesis, and cancer. These Rac-GAPs are regulated by the lipid second messenger diacylglycerol (DAG) generated by tyrosine-kinases such as the epidermal growth factor receptor (EGFR). Here we identify an atypical Pro-rich motif in chimaerins that binds to the adaptor protein Nck1. Unlike most Nck1 partners, chimaerins bind to the third SH3 domain of Nck1. This association is mediated by electrostatic interactions of basic residues within the Pro-rich motif with acidic clusters in the SH3 domain. EGF promotes the binding of β2-chimaerin to …

Neurogenesis Continues In The Third Trimester Of Pregnancy And Is Suppressed By Premature Birth, Nada Zecevic

UCHC Articles - Research

Premature infants exhibit neurodevelopmental delay and reduced growth of the cerebral cortex. However, the underlying mechanisms have remained elusive. Therefore, we hypothesized that neurogenesis in the ventricular and subventricular zones of the cerebral cortex would continue in the third trimester of pregnancy, and that preterm birth would suppress neurogenesis. To test our hypotheses, we evaluated autopsy materials from human fetuses and preterm infants of 16–35 gestational weeks (gw). We noted that both cycling and non-cycling Sox2⁺ radial glial cells as well as Tbr2⁺ intermediate progenitors were abundant in human preterm infants until 28 gw. However, their densities consistently …

Retrospective Study Of Microorganisms Associated With Vascular Access Infections In Hemodialysis Patients, Andre A. Kaplan, Richard S. Feinn, Rajesh V. Lalla

UCHC Articles - Research

Objective

To assess microorganisms associated with vascular access-associated infections (VAIs) in hemodialysis patients, with respect to possible origin from the mouth.

Study Design

A retrospective and comparative analysis of the microbes associated with VAI in hemodialysis patients treated during a 10-year period was performed using the Human Oral Microbiome Database (HOMD).

Results

Of 218 patient records identified, 65 patients collectively experienced 115 VAI episodes. The most common microorganisms involved were Staphylococcus aureus (49.6% of infections), Staphylococcus epidermidis (10.4%), Serratia marcescens (10.4%), Pseudomonas aeruginosa (9.6%), and Enterococcus faecalis / fecum (8.7%). None of these was found in 1% or more of …

Copper Signaling In The Mammalian Nervous System: Synaptic Effects, Eric D. Gaier, Betty A. Eipper, Richard E. Mains

UCHC Articles - Research

Copper (Cu) is an essential metal present at high levels in the CNS. Its role as a co-factor in mitochondrial ATP production and in other essential cuproenzymes is well defined. Menkes and Wilson’s diseases are severe neurodegenerative conditions that demonstrate the importance of Cu transport into the secretory pathway. Brain levels of Cu, which is almost entirely protein bound, exceed extracellular levels by more than a hundred-fold. Cu stored in the secretory pathway is released in a Ca²⁺-dependent manner and can transiently reach concentrations over 100 µM at synapses. The ability of low µM levels of Cu to …

Variation In Mu-Opioid Receptor Gene (Oprm1) As A Moderator Of Naltrexone Treatment To Reduce Heavy Drinking In A High Functioning Cohort, Jonathan M. Covault

UCHC Articles - Research

Background

It is well known that naltrexone, an FDA-approved medication for treatment of alcohol dependence, is effective for only a subset of individuals. Recent studies have examined the utility of a functional A118G single nucleotide polymorphism (SNP) of the mu-opioid receptor gene (OPRM1) as a predictor of naltrexone treatment response. Although the findings to date have generally been consistent with a moderating effect of the SNP, further evaluation of this hypothesis is warranted.

Objective

To evaluate whether problem drinkers with one or two copies of the 118G allele respond better to naltrexone treatment. The treatment goal in this cohort of …

Millon Behavioral Medicine Diagnostic (Mbmd) Predicts Health-Related Quality Of Life (Hrqol) Over Time Among Men Treated For Localized Prostate Cancer, Dean G. Cruess

UCHC Articles - Research

Prostate cancer treatment presents multiple challenges that can negatively affect health-related quality of life (HrQoL), and which may be further compromised by maladaptive personality styles and psychological adjustment difficulties. This study examined the utility of a comprehensive psychosocial screening tool to identify psychosocial traits that prospectively predict HrQoL status among men treated for localized prostate cancer. The Millon Behavioral Medicine Diagnostic (MBMD) was administered to 66 men (mean age 68 years, 59% Caucasian) treated by either radical prostatectomy or radiotherapy along with standard measures of general and prostate cancer-specific quality of life assessed at a 12-month follow-up. Higher scores on …