Publications by authors named "Eric Barbato"

7 Publications

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Circadian characteristics of the rest-activity rhythm, executive function, and glucose fluctuations in young adults with type 1 diabetes.

Chronobiol Int 2021 Jun 15:1-11. Epub 2021 Jun 15.

Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, Ohio, USA.

Circadian alignment is an important element in individual health, and one behavioral marker, rest-activity rhythm, could influence self-management in young adults with type 1 diabetes (T1D). Little is known about the rest-activity rhythms, executive function, and glycemia among young adults with type 1 diabetes (T1D). The purpose of this study was to evaluate parametric and nonparametric circadian characteristics of the rest-activity rhythm and the associations between these variables, sleep-wake behavior, executive function, and glycemia among young adults with T1D. Young adults with T1D, recruited from diabetes clinics, wore wrist actigraphs and a continuous glucose monitor (CGM) concurrently for 6-14 days. Participants completed a 3-minute Trail Making Test on paper and electronic questionnaires - 8-item PROMIS v1.0 Emotional Distress Scale, 17-item Diabetes Distress Scale, including twice-daily Pittsburgh sleep diaries. Cosinor and nonparametric analyses were used to compute the rest-activity rhythm parameters, and linear regression modeling procedures were performed to determine the associations among the study variables. The sample included 46 young adults (mean age 22.3 ± 3.2; 32.6% male; 84.8% non-Hispanic White, HbA1c mean 7.2 ± 1.1%, BMI mean 27.0 ± 4.4 kg/m). A number of parametric associations were observed between a stronger rhythm, better objective sleep-wake characteristics, and less daytime sleepiness. Nonparametric circadian parameters were significantly associated with several outcomes: a stronger rhythm adherence (higher inter-daily stability) with better objective sleep-wake characteristics, better executive function, lower diabetes distress, less hyperglycemia risk, and more time spent in hypoglycemia/hypoglycemia risk; and a more robust rhythm (higher relative amplitude) with better objective sleep-wake characteristics and more time spent in hypoglycemia/higher hypoglycemia risk. Future work should be directed at designs that test causality, such as interventions directed at the strength and stability of rest-activity rhythms, for the potential to improve glucoregulation and other diabetes outcomes.
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http://dx.doi.org/10.1080/07420528.2021.1932987DOI Listing
June 2021

Tubulin Polymerization Promoting Protein Affects the Circadian Timing System in C57Bl/6 Mice.

J Circadian Rhythms 2021 May 20;19. Epub 2021 May 20.

Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland Ohio, US.

The circadian timing system (CTS) is a complex set of cyclic cellular mechanisms which serve to synchronize discrete cell groups across multiple organ systems to adapt the bodys physiology to a (roughly) 24-hour clock. Many genes and hormones have been shown to be strongly associated with the CTS, some of which include the genes , and , and the hormone melatonin. Previous data suggest that microtubule dynamics play an important role in melatonin function as it relates to the CTS in vitro, though this relationship has never been explored in vivo. The purpose of this study was to determine whether disruption of microtubule regulation in C57Bl/6 mice results in measurable changes to the CTS. To study the potential effects of microtubule dynamics on the CTS in vivo, we utilized a mouse model of microtubule instability, knocked out for the tubulin polymerization promoting protein gene (), comparing them to their wild type (WT) littermates in three categories: locomotor activity (in light/dark and dark/dark photoperiods), serial clock gene expression, and serial serum melatonin concentration. These comparisons showed differences in all three categories, including significant differences in locomotor characteristics under dark/dark conditions. Our findings support and extend previous reports that microtubule dynamics are a modulator of circadian rhythm regulation likely through a mechanism involving melatonin induced phase shifting.
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http://dx.doi.org/10.5334/jcr.207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139294PMC
May 2021

Genetic Variation Near chrXq22-q23 Is Linked to Emotional Functioning in Cystic Fibrosis.

Biol Res Nurs 2020 07 11;22(3):319-325. Epub 2020 May 11.

Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA.

Introduction: Cystic fibrosis (CF) is an autosomal recessive disease that affects many organ systems, most notably the pulmonary and gastrointestinal systems. Through genome-wide association studies, multiple genetic regions modifying CF-related pulmonary and gastrointestinal symptoms have been identified, but translation of these findings to clinical benefit remains elusive. Symptom variation in CF patients has been associated with changes in health-related quality of life (HRQOL), but the relationship between CF symptom-modifying genetic loci and HRQOL has not been explored. The purpose of this study was to determine whether two previously identified genetic modifiers of CF-related pathology also modify the subscales of HRQOL.

Methods: HRQOL and genotype data were obtained and analyzed. Linear regressions were used to examine the amount of variance in HRQOL subscales that could be explained by genotype for each modifier locus.

Results: A significant regression equation was found between genotype for rs5952223, a variant near chrXq22-q23, and emotional functioning in a sample of 129 CF patients.

Discussion: These data suggest that genotype for this single-nucleotide polymorphism is associated with emotional functioning in CF patients and highlight this genetic region as a potential therapeutic target, irrespective of CF transmembrane conductance regulator genotype.
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http://dx.doi.org/10.1177/1099800420924125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492775PMC
July 2020

Dysregulation of Circadian Rhythm Gene Expression in Cystic Fibrosis Mice.

J Circadian Rhythms 2019 Apr 18;17. Epub 2019 Apr 18.

Case Western Reserve University, US.

Cystic fibrosis (CF) is autosomal recessive disease that affects multiple body systems. CF patients often experience sleep disturbances, altered sleep patterns, and sleep apnea. Sleep in mammals is controlled in part by circadian clock genes, including and . The purpose of this study was to gain a better understanding of the biological underpinnings of disordered sleep experienced in CF. To accomplish this, we evaluated circadian clock gene expression profiles in CF and wildtype mice, divided into two subgroups each based on sleep condition. One subgroup of each genotype was permitted to maintain their sleep-wake cycle while the other was deprived of sleep for six hours prior to sacrifice. Brain, skeletal muscle, jejunum, colon, lung and adipose tissues were collected from each mouse. Quantitative polymerase chain reaction (PCR) was used to quantify expression of and and expression levels were compared between study groups. Our comparisons showed distinct differences between the CF groups and the wildtype groups under both sleep conditions. Additionally, we found the CF mice that had been sleep deprived had severely dysregulated expression of all measured genes in the lung apart from . Our findings suggest that (1) disordered sleep in CF may be caused by circadian system dysregulation and (2) the loss of the cystic fibrosis transmembrane conductance regulator (CFTR) is a causative factor in the dysregulated circadian clock gene expression profiles of CF mice.
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http://dx.doi.org/10.5334/jcr.175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484366PMC
April 2019

Educating Nursing Scientists: Integrating Genetics and Genomics into PhD Curricula.

J Prof Nurs 2019 Mar - Apr;35(2):89-92. Epub 2018 Sep 6.

Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, United States of America; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, United States of America.

Nursing science is a diverse field of study, the scope of which has broadened to more fully incorporate genetics and genomics. In recent years, these topics have become focus areas for many nursing researchers. However, recent evidence suggests that doctoral level nursing students and nursing faculty may be underprepared to conduct independent research using genomic approaches. Furthermore, genetics and genomics are severely underrepresented in doctoral level nursing curricula across the United States. This article suggests a thorough, yet manageable three-part curriculum designed to educate doctoral level nursing students on genetics, genomics, and their use in nursing science. Recommendations are then given for the integration of the curriculum into existing nursing PhD programs.
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http://dx.doi.org/10.1016/j.profnurs.2018.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612370PMC
April 2019

AGTR2 absence or antagonism prevents cystic fibrosis pulmonary manifestations.

J Cyst Fibros 2019 01 22;18(1):127-134. Epub 2018 Jun 22.

Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA.

Background: Pulmonary disease remains the primary cause of morbidity and mortality for individuals with cystic fibrosis (CF). Variants at a locus on the X-chromosome containing the type 2 angiotensin II receptor gene (AGTR2) were identified by a large GWAS as significantly associating with lung function in CF patients. We hypothesized that manipulating the angiotensin-signaling pathway may yield clinical benefit in CF.

Methods: Genetic subset analysis was conducted on a local CF cohort to extend the GWAS findings. Next, we evaluated pulmonary function in CF mice with a deleted AGTR2 gene, and in those who were given subcutaneous injections of PD123,319, a selective AGTR2 antagonist for 12 weeks beginning at weaning.

Results: The genetic subset analysis replicated the initial GWAS identified association, and confirmed the association of this locus with additional lung function parameters. Studies in genetically modified mice established that absence of the AGTR2 gene normalized pulmonary function indices in two independent CF mouse models. Further, we determined that pharmacologic antagonism of AGTR2 improved overall pulmonary function in CF mice to near wild-type levels.

Conclusions: These results identify that reduced AGTR2 signaling is beneficial to CF lung function, and suggest the potential of manipulating the angiotensin-signaling pathway for treatment and/or prevention of CF pulmonary disease. Importantly, the beneficial effects were not CF gene mutation dependent, and were able to be reproduced with pharmacologic antagonism. As there are clinically approved drugs available to target the renin-angiotensin signaling system, these findings may be quickly translated to human clinical trials.
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http://dx.doi.org/10.1016/j.jcf.2018.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6830504PMC
January 2019

Early pulmonary disease manifestations in cystic fibrosis mice.

J Cyst Fibros 2016 11 24;15(6):736-744. Epub 2016 May 24.

Department of Medicine, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Medicine, Louis Stokes Cleveland VA Medical Center, Cleveland, OH 44106, United States.

Background: Altered pulmonary function is present early in the course of cystic fibrosis (CF), independent of documented infections or onset of pulmonary symptoms. New initiatives in clinical care are focusing on detection and characterization of preclinical disease. Thus, animal models are needed which recapitulate the pulmonary phenotype characteristic of early stage CF.

Methods: We investigated young CF mice to determine if they exhibit pulmonary pathophysiology consistent with the early CF lung phenotype. Lung histology and pulmonary mechanics were examined in 12- to 16-week-old congenic C57bl/6 F508del and R117H CF mice using a forced oscillation technique (flexiVent).

Results: There were no significant differences in the resistance of the large airways. However, in both CF mouse models, prominent differences in the mechanical properties of the peripheral lung compartment were identified including decreased static lung compliance, increased elastance and increased tissue damping. CF mice also had distal airspace enlargement with significantly increased mean linear intercept distances.

Conclusions: An impaired ability to stretch and expand the peripheral lung compartment, as well as increased distances between gas exchange surfaces, were present in young CF mice carrying two independent Cftr mutations. This altered pulmonary histopathophysiology in the peripheral lung compartment, which develops in the absence of infection, is similar to the early lung phenotype of CF patients.
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http://dx.doi.org/10.1016/j.jcf.2016.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121081PMC
November 2016
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