Digital Commons Network^™

Phenotypical Characterization Of Human Rhinovirus Infections In Severely Premature Children, Geovanny F. Perez, Bassem Kurdi, Rosemary Megalaa, Krishna Pancham, Shehlanoor Huseni, Natalia Isaza, Carlos E. Rodriguez-Martinez, Dinesh Pillai, Gustavo Nino

Pediatrics Faculty Publications

Background: Human Rhinovirus (HRV) has been identified as the most common cause of acute respiratory infections and hospitalizations in premature children. It is unclear if premature children are more susceptible to HRV due to their decreased pulmonary reserve or because they have enhanced lower airway reactivity to HRV.

Methods: We conducted a retrospective analysis of the clinical respiratory presentation of all PCR-confirmed HRV infections in full-term and premature children aged ≤ 3 years in our institution. Standardized respiratory distress scores were developed to examine lower airway obstruction (i.e., wheezing, hyperinflation, and sub-costal retractions) along with markers of decreased pulmonary reserve …

Additive Drug-Specific And Sex-Specific Risks Associated With Co-Use Of Marijuana And Tobacco During Pregnancy: Evidence From 3 Recent Developmental Cohorts (2003-2015)., Suena H Massey, Daniel K Mroczek, David Reiss, Emily S Miller, Jessica A Jakubowski, Eileen K Graham, Shannon M Shisler, Meaghan Mccallum, Marilyn A. Huestis, Jody M Ganiban, Daniel S Shaw, Leslie D Leve, Rina D Eiden, Laura R Stroud, Jenae M Neiderhiser

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Methodologic challenges related to the concomitant use (co-use) of substances and changes in policy and potency of marijuana contribute to ongoing uncertainty about risks to fetal neurodevelopment associated with prenatal marijuana use. In this study, we examined two biomarkers of fetal neurodevelopmental risk-birth weight and length of gestation-associated with prenatal marijuana use, independent of tobacco (TOB), alcohol (ALC), other drug use (OTH), and socioeconomic risk (SES), in a pooled sample (N = 1191) derived from 3 recent developmental cohorts (2003-2015) with state-of-the-art substance use measures. We examined differential associations by infant sex, and multiplicative effects associated with co-use of …

Use Of International Classification Of Diseases, Ninth Revision Codes For Obesity: Trends In The United States From An Electronic Health Record-Derived Database., Michelle Mocarski, Ye Tian, B. Gabriel Smolarz, John Mcana, Albert Crawford

College of Population Health Faculty Papers

Obesity is a potentially modifiable risk factor for many diseases, and a better understanding of its impact on health care utilization, costs, and medical outcomes is needed. The ability to accurately evaluate obesity outcomes depends on a correct identification of the population with obesity. The primary objective of this study was to determine the prevalence and accuracy of International Classification of Diseases, Ninth Revision (ICD-9) coding for overweight and obesity within a US primary care electronic health record (EHR) database compared against actual body mass index (BMI) values from recorded clinical patient data; characteristics of patients with obesity who did …

Project Echo Telementoring Intervention For Managing Chronic Pain In Primary Care: Insights From A Qualitative Study, Leslie Carlin, Jane Zhao, Ruth Dubin, Paul Taenzer, Hannah Sidrak, Andrea Furlan

Project ECHO Bibliography

Objective: Family physicians in Canada receive little training in chronic pain management; concomitantly, they face increasing pressure to reduce their prescribing of opioids. Project ECHO Ontario Chronic Pain/Opioid Stewardship (ECHO) is a telementoring intervention for primary care practitioners that enhances their pain management skills. This qualitative study reports participants' experiences and assessment of ECHO.

Design: An opportunistic sample of multidisciplinary primary care providers attending one of three residential weekend workshops participated in focus group discussions.

Setting: University or hospital facilities in Toronto, Thunder Bay, and Kingston, Ontario, Canada.

Subjects: Seventeen physicians and 20 allied health professionals.

Methods: Six focus group …

Age Adjusted Hematopoietic Stem Cell Transplant Comorbidity Index Predicts Survival In A T-Cell Depleted Cohort, Hayder Saeed, Swati Yalamanchi, Meng Liu, Emily Van Meter, Zartash Gul, Gregory Monohan, Dianna Howard, Gerhard C. Hildebrandt, Roger Herzig

Markey Cancer Center Faculty Publications

Objectives: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria.

Methods: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was …

Health Status Disparities By Sex, Race/Ethnicity, And Socioeconomic Status In Outpatients With Heart Failure., Yevgeniy Khariton, Michael E Nassif, Laine Thomas, Gregg C Fonarow, Xiaojuan Mi, Adam D Devore, Carol Duffy, Puza P Sharma, Nancy M Albert, J Herbert Patterson, Javed Butler, Adrian F Hernandez, Fredonia B Williams, Kevin Mccague, John A Spertus

Open Access Publications

OBJECTIVES: This study sought to describe the health status of outpatients with heart failure and reduced ejection fraction (HFrEF) by sex, race/ethnicity, and socioeconomic status (SES).

BACKGROUND: Although a primary goal in treating patients with HFrEF is to optimize health status, whether disparities by sex, race/ethnicity, and SES exist is unknown.

METHODS: In the CHAMP-HF (Change the Management of Patients with Heart Failure) registry, the associations among sex, race, and SES and health status, as measured by the Kansas City Cardiomyopathy Questionnaire-overall summary (KCCQ-os) score (range 0 to 100; higher scores indicate better health status) was compared among 3,494 patients …

New Insights Into Predictors Of Cardiac Implantable Electronic Device Infection, Hossein Sadeghi, Abolfath Alizadehdiz, Amirfarjam Fazelifar, Zahra Emkanjoo, Majid Haghjoo

The Texas Heart Institute Journal

Infection is an important complication of cardiac implantable electronic device procedures. To further study the factors associated with infection, we retrospectively reviewed the records of 3,205 consecutive patients who had undergone de novo or revision cardiac electronic device implantation at our institution from March 2011 through March 2015. We recorded all infections and specified whether they were related to the characteristics of the patient, device, or procedure. To identify predictors of infection, we performed multivariate analysis.

Device infections were identified in 85 patients (2.7%), at a mean follow-up time of 27 ± 11 months. The main predictors of device infection …

Molecular Gut Content Analysis Of Different Spider Body Parts, Nuria Macías-Hernández, Kacie J. Athey, Vanina Tonzo, Owen S. Wangensteen, Miquel Arnedo, James D Harwood

Entomology Faculty Publications

Molecular gut-content analysis has revolutionized the study of food webs and feeding interactions, allowing the detection of prey DNA within the gut of many organisms. However, successful prey detection is a challenging procedure in which many factors affect every step, starting from the DNA extraction process. Spiders are liquid feeders with branched gut diverticula extending into their legs and throughout the prosoma, thus digestion takes places in different parts of the body and simple gut dissection is not possible. In this study, we investigated differences in prey detectability in DNA extracts from different parts of the spider´s body: legs, prosoma …

Palladin Is A Neuron-Specific Translational Target Of Mtor Signaling That Regulates Axon Morphogenesis, Yusuke Umegaki, Antonio Martínez Brotons, Yui Nakanishi, Zhongyue Luo, Hanlu Zhang, Azad Bonni, Yoshiho Ikeuchi

Open Access Publications

The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates …

Internet And Social Media Access Among Youth Experiencing Homelessness: Mixed-Methods Study., Lauren A. Houdek Vonholtz, Rosemary Frasso, Jesse M. Golinkoff, Alicia J. Lozano, Alexandra Hanlon, Nadia Dowshen

College of Population Health Faculty Papers

BACKGROUND: Youth experiencing homelessness are at a risk for a variety of adverse outcomes. Given the widespread use of the internet and social media, these new technologies may be used to address their needs and for outreach purposes. However, little is known about how this group uses these resources.

OBJECTIVE: This study investigated how homeless adolescents use these technologies for general and health-related purposes, whether the scope of their use changes with housing status, and their interest in a website dedicated to youth experiencing homelessness.

METHODS: A convenience sample of youth aged 18 to 21 years was recruited from a …

Decreasing Recurrent Bowel Obstructions, Improving Quality Of Life With Physiotherapy: Controlled Study, Amanda D Rice, Kimberley Patterson, Evette D Reed, Belinda F Wurn, Kristen Robles, Bernhard Klingenberg, Leonard B Weinstock, Janey S. A. Pratt, C. Richard King Iii, Lawrence J Wurn

Open Access Publications

AIM: To compare (1) quality of life and (2) rate of recurrent small bowel obstructions (SBO) for patients treated with novel manual physiotherapy

METHODS: One hundred and three subjects (age 19-89) with a history of recurrent adhesive SBO were treated with a manual physiotherapy called the Clear Passage Approach (CPA) which focused on decreasing adhesive crosslinking in abdominopelvic viscera. Pre- and post-therapy data measured recurring obstructions and quality of life, using a validated test sent 90 d after therapy. Results were compared to 136 untreated control subjects who underwent the same measurements for subjects who did not receive any therapy, …

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Veterinary Science Faculty Publications

Background

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the …

Iron Isomaltoside Is Superior To Iron Sucrose In Increasing Hemoglobin In Gynecological Patients With Iron Deficiency Anemia., Richard Derman, Eloy Roman, Gioi N. Smith-Nguyen, Maureen M. Achebe, Lars L. Thomsen, Michael Auerbach

Global Health Articles

No abstract provided.

Analysis Of The Immunological Biomarker Profile During Acute Zika Virus Infection Reveals The Overexpression Of Cxcl10, A Chemokine Linked To Neuronal Damage., Felipe Gomes Naveca, Gemilson Soares Pontes, Aileen Yu-Hen Chang, George Allan Villarouco Da Silva, Valdinete Alves Do Nascimento, Dana Cristina Da Silva Monteiro, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications and little is known about Zika immunopathogenesis.

OBJECTIVES: To define the immunologic biomarkers that correlate with acute ZIKV infection.

METHODS: We characterized the levels of circulating cytokines, chemokines, and growth factors in 54 infected patients of both genders at five different time points after symptom onset using microbeads multiplex immunoassay; comparison to 100 age-matched controls was performed for statistical analysis and data mining.

FINDINGS: ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite …

Judith Jarvis Thomson On Abortion; A Libertarian Perspective, Walter E. Block

DePaul Journal of Health Care Law

Introduction:

Judith Jarvis Thompson, an eminent philosopher from MIT, has written the most widely cited article of all those ever written about abortion. She likens the fetus to a trespasser. Suppose you wake up in bed next to a famous violinist who is (innocently) connected to your kidney, through a sort of umbilical cord, without which he will die. What rights does he have? What obligations do you have? Using this brilliant analogy to pregnancy, she sheds light on the abortion controversy.

Method:

The method used in the present paper is to widely quote Thompson’s (1971) essay, and then to …

Exacerbation Recovery Patterns In Newly Diagnosed Or Maintenance Treatment-Naïve Patients With Copd: Secondary Analyses Of Ticari 1 Trial Data, David M. Mannino, Emmanuelle M. Clerisme-Beaty, Joanne Franceschina, Naitee Ting, Nancy K. Leidy

Preventive Medicine and Environmental Health Faculty Publications

Background: Little is known about the recovery patterns from acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in newly diagnosed or maintenance treatment-naïve patients with COPD. This study describes the course of AECOPD in these patients at the time of treatment for the symptoms of acute respiratory tract infection (RTI).

Methods: This study was a secondary analysis of data from a 12-week, randomized clinical trial (TICARI 1) testing the efficacy and safety of once-daily tiotropium 18 µg maintenance therapy versus placebo in newly diagnosed or maintenance treatment-naïve COPD patients with acute RTI symptoms for ≤7 days. Patients received standard care …

Disruption Of Neonatal Cardiomyocyte Physiology Following Exposure To Bisphenol-A., Manelle Ramadan, Meredith Sherman, Rafael Jaimes, Ashika Chaluvadi, Luther Swift, Nikki Gillum Posnack

Pediatrics Faculty Publications

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat …

Examining Ecological Constraints On The Intergenerational Transmission Of Attachment Via Individual Participant Data Meta-Analysis, Marije L Verhage, R M Pasco Fearon, Carlo Schuengel, Marinus H Van Ijzendoorn, Marian J Bakermans-Kranenburg, Sheri Madigan, Glenn I Roisman, Mirjam Oosterman, Kazuko Y Behrens, Maria S Wong, Sarah Mangelsdorf, Lynn E. Priddis, Karl-Heinz Brisch, Collaboration On Attachment Transmission Synthesis

Research outputs 2014 to 2021

Parents' attachment representations and child-parent attachment have been shown to be associated, but these associations vary across populations (Verhage et al., 2016). The current study examined whether ecological factors may explain variability in the strength of intergenerational transmission of attachment, using individual participant data (IPD) meta-analysis. Analyses on 4,396 parent-child dyads (58 studies, child age 11-96 months) revealed a combined effect size of r = .29. IPD meta-analyses revealed that effect sizes for the transmission of autonomous-secure representations to secure attachments were weaker under risk conditions and weaker in adolescent parent-child dyads, whereas transmission was stronger for older children. Findings …

Protocol For A Randomised Trial Of Higher Versus Lower Intensity Patient-Provider Communication Interventions To Reduce Antibiotic Misuse In Two Paediatric Ambulatory Clinics In The Usa., Kathy Goggin, Andrea Bradley-Ewing, Angela Myers, Brian R. Lee, Emily A. Hurley, Kirsten B. Delay, Sarah Schlachter, Areli Ramphal, Kimberly Pina, David Yu, Kirsten Weltmer, Sebastian Linnemayr, Christopher C. Butler, Jason G. Newland

Manuscripts, Articles, Book Chapters and Other Papers

INTRODUCTION: Children with acute respiratory tract infections (ARTIs) are prescribed up to 11.4 million unnecessary antibiotic prescriptions annually. Inadequate parent-provider communication is a chief contributor, yet efforts to reduce overprescribing have only indirectly targeted communication or been impractical. This paper describes our multisite, parallel group, cluster randomised trial comparing two feasible interventions for enhancing parent-provider communication on the rate of inappropriate antibiotic prescribing (primary outcome) and revisits, adverse drug reactions and parent-rated quality of shared decision-making, parent-provider communication and visit satisfaction (secondary outcomes).

METHODS/ANALYSIS: We will attempt to recruit all eligible paediatricians and nurse practitioners (currently 47) at an academic …

Trpv1 And The Mcp-1/Ccr2 Axis Modulate Post-Uti Chronic Pain., John Rosen, Ryan E. Yaggie, Patrick J. Woida, Richard J. Miller, Anthony J. Schaeffer, David J. Klumpp

Manuscripts, Articles, Book Chapters and Other Papers

The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas …

Teens Implementing A Childhood Obesity Prevention Program In The Community: Feasibility And Perceptions Of A Partnership With Hsta And Icook 4-H., Rebecca L. Hagedorn, Jade A. White, Lisa Franzen-Castle, Sarah E. Colby, Kendra Kattelmann, Adrienne A. White, Melissa D. Olfert

Health and Nutritional Sciences Faculty Publications

High school student researchers and teen leaders from the Health Science Technology Academy (HSTA), under the supervision of HSTA teachers, led a childhood obesity prevention (COP) program (iCook 4-H). The objective was to evaluate the feasibility and perceptions of having teen leaders implement a COP program for dyads of youth (9⁻10 years old) and their primary adult food preparer. Behavior change and perceptions were assessed through surveys and open-ended interviews. Across eight HSTA organizations, 43 teen leaders participated in teaching the iCook 4-H program to 24 dyads. Increased frequency of culinary skills, physical activity and mealtime behavior were reported by …

Dancing In The Airfield: The Women Of The 46th Taman Guards Aviation Regiment And Their Journey Through War And Womanhood, Yasmine L. Vaughan

Senior Honors Projects, 2010-2019

During the Second World War, the Soviet Union became the first country in the world to allow women to join the Air Force. Three regiments were formed, comprised of all female personnel. The three regiments flew over 30,000 combat missions and produced thirty Heroes of the Soviet Union (HSUs) in their three years of service. The 588^th, later renamed the 46^th, was the most successful and well-known of the female regiments, famous for its combat record and stunning achievements.This paper seeks to put into context the unique social constructions that allowed for the recruitment, training, and …

Understanding The Relationship Between The Neurologic Pupil Index And Constriction Velocity Values., Ifeoluwa Shoyombo, Venkatesh Aiyagari, Sonja E Stutzman, Folefac Atem, Michelle Hill, Stephen A Figueroa, Chad Miller, Amber Howard, Daiwai M Olson

Neuroscience Articles

The pupillary light reflex (PLR) describes the response when light hits the retina and sends a signal (cranial nerve II) to the Edinger-Westphal Nucleus which via cranial nerve III results in pupillary constriction. The Neurological Pupil indexTM (NPi) and pupil constriction velocity (CV) are two distinct variables that can be observed and measured using a pupillometer. We examine NPi and CV in 27,462 pupil readings (1,617 subjects). NPi values < 3.0 and a CV < 0.8 mm/sec were considered abnormal. Regression was used to clarify the effect of pupil size and repeated measures. An odds ratio of abnormal CV given normal NPi (and vice versa) was computed using the glimmixed (SAS) regression. Of 27,462 readings, 49.2% revealed bilaterally normal NPi wtih brisk CV, and 10.8% revealed bilaterally abnormal NPi and slow CV; 9.1% with unilaterally normal NPi and brisk CV where the opposite pupil had an abnormal NPi and slow CV. The remaining 30.9% revealed that one or both PLR had either a normal NPi with slow CV, or abnormal NPi with brisk CV. Brisk CV does not rule out an abnormal PLR; slow CV does not rule in abnormal PLR. Practitioners should consider these implications when interpreting pupillometry readings.

Parabiosis And Single-Cell Rna Sequencing Reveal A Limited Contribution Of Monocytes To Myofibroblasts In Kidney Fibrosis, Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K Schneider, Benjamin D Humphreys

Open Access Publications

Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney …

Dietary Diversity Predicts The Adequacy Of Micronutrient Intake In Pregnant Adolescent Girls And Women In Bangladesh, But Use Of The 5-Group Cutoff Poorly Identifies Individuals With Inadequate Intake, Phuong Hong Nguyen, Lieven Huybregts, Tina G. Sanghvi, Lan Mai Tran, Edward A. Frongillo Jr., Purnima Menon, Marie T. Ruel

Faculty Publications

Background: The Minimum Dietary Diversity for Women (MDD-W) indicator based on a 10-food group women dietary diversity score (WDDS-10) has been validated to assess dietary quality in nonpregnant women. Little is known about its applicability in pregnant women, and specifically pregnant adolescent girls with higher nutrient requirements. Objectives: This study aimed to 1) compare the adequacy of micronutrient intakes between pregnant adolescent girls and women, 2) examine the performance of WDDS-10 in predicting the mean probability of adequacy (MPA) of 11 micronutrients, and 3) assess how well the MDD-W cutoff of 5 groups performed in pregnant adolescent girls and women. …

Type-2 Diabetes Mellitus Reduces Cortical Thickness And Decreases Oxidative Metabolism In Sensorimotor Regions After Stroke., Jennifer K Ferris, Sue Peters, Katlyn E Brown, Katherine Tourigny, Lara A Boyd

Physical Therapy Publications

Individuals with type-2 diabetes mellitus experience poor motor outcomes after ischemic stroke. Recent research suggests that type-2 diabetes adversely impacts neuronal integrity and function, yet little work has considered how these neuronal changes affect sensorimotor outcomes after stroke. Here, we considered how type-2 diabetes impacted the structural and metabolic function of the sensorimotor cortex after stroke using volumetric magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). We hypothesized that the combination of chronic stroke and type-2 diabetes would negatively impact the integrity of sensorimotor cortex as compared to individuals with chronic stroke alone. Compared to stroke alone, individuals with …

Trunk Motion Visual Feedback During Walking Improves Dynamic Balance In Older Adults: Assessor Blinded Randomized Controlled Trial., Eric Anson, Lei Ma, Tippawan Meetam, Elizabeth Thompson, Roshita Rathore, Victoria Dean, John Jeka

Department of Physical Therapy Faculty Papers

BACKGROUND: Virtual reality and augmented feedback have become more prevalent as training methods to improve balance. Few reports exist on the benefits of providing trunk motion visual feedback (VFB) during treadmill walking, and most of those reports only describe within session changes.

RESEARCH QUESTION: To determine whether trunk motion VFB treadmill walking would improve over-ground balance for older adults with self-reported balance problems.

METHODS: 40 adults (75.8 years (SD 6.5)) with self-reported balance difficulties or a history of falling were randomized to a control or experimental group. Everyone walked on a treadmill at a comfortable speed 3×/week for 4 weeks …

Population-Specific Genetic Modification Of Huntington's Disease In Venezuela., Michael J Chao, Kyung-Hee Kim, Jun Wan Shin, Diane Lucente, Vanessa C Wheeler, Hong Li, Jared C Roach, Leroy Hood, Nancy S Wexler, Laura B Jardim, Peter Holmans, Lesley Jones, Michael Orth, Seung Kwak, Marcy E Macdonald, James F Gusella, Jong-Min Lee

Articles, Abstracts, and Reports

Modifiers of Mendelian disorders can provide insights into disease mechanisms and guide therapeutic strategies. A recent genome-wide association (GWA) study discovered genetic modifiers of Huntington's disease (HD) onset in Europeans. Here, we performed whole genome sequencing and GWA analysis of a Venezuelan HD cluster whose families were crucial for the original mapping of the HD gene defect. The Venezuelan HD subjects develop motor symptoms earlier than their European counterparts, implying the potential for population-specific modifiers. The main Venezuelan HD family inherits HTT haplotype hap.03, which differs subtly at the sequence level from European HD hap.03, suggesting a different ancestral origin …

Amylin And Diabetic Cardiomyopathy – Amylin-Induced Sarcolemmal Ca2+ Leak Is Independent Of Diabetic Remodeling Of Myocardium, Miao Liu, Amanda Hoskins, Nirmal Verma, Donald M. Bers, Sanda Despa, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Amylin is a pancreatic β-cell hormone co-secreted with insulin, plays a role in normal glucose homeostasis, and forms amyloid in the pancreatic islets of individuals with type-2 diabetes. Aggregated amylin is also found in blood and extra-pancreatic tissues, including myocardium. Myocardial amylin accumulation is associated with myocyte Ca²⁺ dysregulation in diabetic rats expressing human amylin. Whether deposition of amylin in the heart is a consequence of or a contributor to diabetic cardiomyopathy remains unknown. We used amylin knockout (AKO) mice intravenously infused with either human amylin (i.e, the aggregated form) or non-amyloidogenic (i.e., monomeric) rodent amylin to test the …

Potent Immune Modulation By Medi6383, An Engineered Human Ox40 Ligand Igg4p Fc Fusion Protein., Michael D Oberst, Catherine Augé, Chad Morris, Stacy Kentner, Kathy Mulgrew, Kelly Mcglinchey, James Hair, Shino Hanabuchi, Qun Du, Melissa Damschroder, Hui Feng, Steven Eck, Nicholas Buss, Lolke De Haan, Andrew J Pierce, Haesun Park, Andrew Sylwester, Michael K Axthelm, Louis Picker, Nicholas P Morris, Andrew D Weinberg, Scott A Hammond

Articles, Abstracts, and Reports

Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced …