Publications by authors named "Douglas A Granger"

249 Publications

Mission, Organization, and Future Direction of the Serological Sciences Network for COVID-19 (SeroNet) Epidemiologic Cohort Studies.

Open Forum Infect Dis 2022 Jun 27;9(6):ofac171. Epub 2022 Apr 27.

Department of Family and Community Medicine, Ohio State University College of Medicine, Columbus, Ohio, USA.

Background: Global efforts are needed to elucidate the epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the underlying cause of coronavirus disease 2019 (COVID-19), including seroprevalence, risk factors, and long-term sequelae, as well as immune responses after vaccination across populations and the social dimensions of prevention and treatment strategies.

Methods: In the United States, the National Cancer Institute in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to study coronavirus disease 2019. The network comprises multidisciplinary researchers bridging gaps and fostering collaborations among immunologists, epidemiologists, virologists, clinicians and clinical laboratories, social and behavioral scientists, policymakers, data scientists, and community members. In total, 49 institutions form the SeroNet consortium to study individuals with cancer, autoimmune disease, inflammatory bowel diseases, cardiovascular diseases, human immunodeficiency virus, transplant recipients, as well as otherwise healthy pregnant women, children, college students, and high-risk occupational workers (including healthcare workers and first responders).

Results: Several studies focus on underrepresented populations, including ethnic minorities and rural communities. To support integrative data analyses across SeroNet studies, efforts are underway to define common data elements for standardized serology measurements, cellular and molecular assays, self-reported data, treatment, and clinical outcomes.

Conclusions: In this paper, we discuss the overarching framework for SeroNet epidemiology studies, critical research questions under investigation, and data accessibility for the worldwide scientific community. Lessons learned will help inform preparedness and responsiveness to future emerging diseases.
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http://dx.doi.org/10.1093/ofid/ofac171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129196PMC
June 2022

Effect of animal assisted interactions on activity and stress response in children in acute care settings.

Compr Psychoneuroendocrinol 2021 Nov 31;8:100076. Epub 2021 Jul 31.

Clinical Associate Professor of Pediatrics, University of Arizona College of Medicine; Division of Critical Care Medicine, Phoenix Children's Hospital, 1919 E. Thomas Road, Phoenix, AZ, 85016, USA.

Objective: Determine the effects of animal assisted interactions (AAI) on activity and stress response in pediatric acute care settings.

Design: Randomized treatment control design.

Setting: Inpatient pediatric acute care units (PICU, CVICU and Hematology/Oncology).

Patients: Eighty pediatric inpatients (49% male) age 2-19 years.

Intervention: The AAI experimental group patients interacted with therapy dog teams for 5-10 min and the comparison group patients continued their current activity without an AAI visit.

Measurement And Results: Salivary cortisol, activity level, and mood were assessed before and after AAI. AAI was associated with a decrease in cortisol levels and increases in mood and activity.

Conclusion: AAI benefits children in pediatric acute care units.
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http://dx.doi.org/10.1016/j.cpnec.2021.100076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9216416PMC
November 2021

The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.

mSphere 2022 Jun 15:e0019322. Epub 2022 Jun 15.

Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.

In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies" (https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-network). SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology standard reference material and first WHO international standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. SeroNet institutions reported development of a total of 27 enzyme-linked immunosorbent assay (ELISA) methods, 13 multiplex assays, and 9 neutralization assays and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. In conclusion, SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons. SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these assays using reference materials to establish standardized reporting units. This will facilitate clinical interpretation of serology results and cross-comparison of research data.
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http://dx.doi.org/10.1128/msphere.00193-22DOI Listing
June 2022

Cognitive behavioral therapy versus general health education for family caregivers of individuals with heart failure: a pilot randomized controlled trial.

BMC Geriatr 2022 04 5;22(1):281. Epub 2022 Apr 5.

School of Nursing, University of California, Los Angeles, CA, USA.

Background: While support from family caregivers is essential in the care of patients with heart failure (HF), caregiving places a considerable burden on family caregivers. We examined the preliminary effects of cognitive behavioral therapy (CBT) for caregivers of individuals with HF.

Methods: In this pilot randomized controlled trial, patients with HF and their primary family caregivers (30 dyads) were randomized into CBT (n = 15) or general health education (GHE, n = 15) groups. Caregivers received 8 weekly individual sessions of either CBT (intervention) or GHE (attention control condition). Caregivers completed questionnaires at baseline, post-intervention, and 6 months. Saliva samples collected from caregivers at baseline and post-intervention were analyzed for salivary cortisol. The cortisol awakening response (CAR) and area under the curve (AUC) were calculated using log-transformed cortisol values. We analyzed data from 26 (14 receiving CBT and 12 receiving GHE) caregivers who received at least one session of CBT or GHE (modified intention-to treat) using linear mixed models. Each model included time, study group, and time-by-study group interaction as fixed effects.

Results: Patients were older (66.94 ± 14.01 years) than caregivers (55.09 ± 15.24 years), and 54% of patients and 54% of caregivers were female. Most caregivers (58%) were spouses. A total of 14 (93%) CBT and 12 (80%) GHE participants received at least 1 session (p = .60), and 11 (73%) CBT and 11 (73%) GHE participants completed all 8 sessions (p = 1.00). There were no significant between-group differences in change for salivary cortisol or psychological outcomes. However, the CBT group had significant within-group improvements in perceived stress (p = .011), stress symptoms (p = .017), depression (p = .002), and anxiety (p = .006) from baseline to post-intervention, while the control group had no significant within-group change in the outcomes except for anxiety (p = .03). The significant improvements observed in the CBT group lasted for 6 months. No adverse effects were observed.

Conclusions: In this pilot trial, although between-group differences in change were not significant, CBT resulted in significant improvements in some psychological outcomes with no improvement in the control group. Our findings suggest the potential of the intervention to alleviate psychological distress in HF caregivers. Further examination in larger randomized trials is warranted.

Trial Registration: ClinicalTrials.gov Identifier: NCT01937936 (Registered on 10/09/2013).
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http://dx.doi.org/10.1186/s12877-022-02996-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8981676PMC
April 2022

Characterizing and Evaluating Diurnal Salivary Uric Acid Across Pregnancy Among Healthy Women.

Front Endocrinol (Lausanne) 2022 18;13:813564. Epub 2022 Mar 18.

Alberta Children's Hospital Research Institute, Calgary, AB, Canada.

Uric acid levels during pregnancy have been examined as a potential indicator of risk for gestational diabetes mellites, hypertension, and related adverse birth outcomes. However, evidence supporting the utility of serum uric acid levels in predicting poor maternal and fetal health has been mixed. The lack of consistent findings may be due to limitations inherent in serum-based biomeasure evaluations, such as minimal repeated assessments and variability in the timing of these assessments. To address these gaps, we examined repeated measurements of diurnal salivary uric acid (sUA) levels in a sample of 44 healthy women across early-mid and late pregnancy. We assessed potential covariates and confounds of sUA levels and diurnal trajectories, as well as associations between maternal weight gain and blood pressure during pregnancy and sUA concentrations. Using multilevel linear models, we found sUA increased across pregnancy and displayed a robust diurnal pattern with the highest concentrations at waking, a steep decline in the early morning, and decreasing levels across the day. Maternal pre-pregnancy BMI, age, prior-night sleep duration, and fetal sex were associated with sUA levels and/or diurnal slopes. Maternal blood pressure and gestational weight gain also showed significant associations with sUA levels across pregnancy. Our results expand upon those found with serum UA measurements. Further, they demonstrate the feasibility of using at-home, minimally-invasive saliva sampling procedures to track UA levels across pregnancy with potential applications for the long-term monitoring of maternal cardiometabolic risk.
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http://dx.doi.org/10.3389/fendo.2022.813564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971544PMC
April 2022

The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.

medRxiv 2022 Mar 14. Epub 2022 Mar 14.

Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

Background: In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies." SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization.

Methods: To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. SARS-CoV-2 serology standard reference material and First WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data.

Results: SeroNet institutions reported development of a total of 27 ELISA methods, 13 multiplex assays, 9 neutralization assays, and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards.

Conclusions: SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 virus and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons.
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http://dx.doi.org/10.1101/2022.02.27.22271399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8902887PMC
March 2022

Salivary S100 calcium-binding protein beta (S100B) and neurofilament light (NfL) after acute exposure to repeated head impacts in collegiate water polo players.

Sci Rep 2022 03 2;12(1):3439. Epub 2022 Mar 2.

Department of Neurology, University of California Irvine, Irvine, CA, 92697-3957, USA.

Blood-based biomarkers of brain injury may be useful for monitoring brain health in athletes at risk for concussions. Two putative biomarkers of sport-related concussion, neurofilament light (NfL), an axonal structural protein, and S100 calcium-binding protein beta (S100B), an astrocyte-derived protein, were measured in saliva, a biofluid which can be sampled in an athletic setting without the risks and burdens associated with blood sampled by venipuncture. Samples were collected from men's and women's collegiate water polo players (n = 65) before and after a competitive tournament. Head impacts were measured using sensors previously evaluated for use in water polo, and video recordings were independently reviewed for the purpose of validating impacts recorded by the sensors. Athletes sustained a total of 107 head impacts, all of which were asymptomatic (i.e., no athlete was diagnosed with a concussion or more serious). Post-tournament salivary NfL was directly associated with head impact frequency (RR = 1.151, p = 0.025) and cumulative head impact magnitude (RR = 1.008, p = 0.014), while controlling for baseline salivary NfL. Change in S100B was not associated with head impact exposure (RR < 1.001, p > 0.483). These patterns suggest that repeated head impacts may cause axonal injury, even in asymptomatic athletes.
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http://dx.doi.org/10.1038/s41598-022-07241-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8891257PMC
March 2022

The Importance of Biobehavioral Research to Examine the Physiological Effects of Racial and Ethnic Discrimination in the Latinx Population.

Front Public Health 2021 10;9:762735. Epub 2022 Jan 10.

Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, Irvine, CA, United States.

A growing body of research is documenting how racial and ethnic populations embody social inequalities throughout the life course. Some scholars recommend the integration of biospecimens representing the hypothalamic-pituitary-adrenal axis, neurological and endocrinological processes, and inflammation to capture the embodiment of inequality. However, in comparison to other racial and ethnic groups, there has been little research examining how Hispanic/Latinx persons embody racial and ethnic discrimination, much less resulting from institutional and structural racism. We provide a rationale for expanding biobehavioral research examining the physiological consequences of racism among Latinx persons. We identify gaps and make recommendations for a future research agenda in which biobehavioral research can expand knowledge about chronic disease inequities among Latinx populations and inform behavioral and institutional interventions. We end by cautioning readers to approach the recommendations in this article as a call to expand the embodiment of racism research to include the diverse Latinx population as the United States addresses racial inequity.
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http://dx.doi.org/10.3389/fpubh.2021.762735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8784784PMC
April 2022

Post-Traumatic Bio-Behavioral Rehabilitation of Adult Female Victims.

Dela J Public Health 2021 Sep 27;7(4):160-166. Epub 2021 Sep 27.

Founder and Chief Scientific Strategy Advisor, Salimetrics LLC and Salivabio LLC; Emeritus Chancellors' Professor, Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine; Adjunct Professor, Johns Hopkins University.

Objective: To determine if low resting basal AM cortisol and flat diurnal cortisol slope that has been reported in female abuse victims, which is dysregulated in the same way in female violent perpetrators, could be corrected and if healthier diurnal cortisol patterns are associated with less aggression in adult female victims.

Design And Methods: A non-experimental, naturalistic study evaluated if bio-behavioral rehabilitation could occur for females living in a Delaware homeless mission and participating in their programs. Basal salivary cortisol (AM, PM & slope), aggression, neurological conditions, general health, alcohol use, having been a victim of abuse, religion, spirituality and forgiveness were evaluated over one month between 2018 and 2019.

Results: T tests revealed significant improvement in mean cortisol (AM, PM & slope), aggression, emotional/ behavioral dyscontrol, and health over one month while participating in the mission's programs. Paired t-tests however were only significant for aggression and health. Healthier cortisol was significantly correlated with greater time since last alcohol, greater time since last abuse, less aggression, better health and greater religion, spirituality and forgiveness.

Conclusion: Community programs could be cost effective methods of post-traumatic bio-behavioral rehabilitation. Forgiveness may play a critical role for abuse victims. A larger sample and more settings are needed, although these findings are promising.
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http://dx.doi.org/10.32481/djph.2021.09.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482978PMC
September 2021

Saliva testing as a means to monitor therapeutic lithium levels in patients with psychiatric disorders: Identification of clinical and environmental covariates, and their incorporation into a prediction model.

Bipolar Disord 2021 11 24;23(7):679-688. Epub 2021 Sep 24.

Department of Epidemiology, University of California Irvine, Irvine, California, USA.

Objective: The narrow therapeutic window of lithium medications necessitates frequent serum monitoring, which can be expensive and inconvenient for the patient. Compared to blood, saliva collection is easier, non-invasive, requires less processing, and can be done without the need for trained personnel. This study investigated the utility of longitudinal salivary lithium level monitoring.

Methods: We measured salivary lithium levels using ICP-OES in n = 169 passive drool samples, collected both as single observations and longitudinally for up to 18 months, from a multi-center cohort of n = 75 patients with bipolar disorder or other psychiatric conditions.

Results: Saliva and serum lithium levels were highly correlated. Adjustment for daily lithium dose, diabetes, and smoking improved this relationship (r = 0.77). Using the adjusted intersubject equation and a patient's salivary lithium value, we observed a strong correlation between the predicted vs. observed serum lithium levels (r = 0.70). Most patients had highly stable saliva/serum ratios across multiple visits, with longitudinal variability significantly greater with age. Use of the intrasubject saliva/serum ratio from a single prior observation had similar predictive power to the use of the adjusted intersubject equation. However, the use of the mean intrasubject ratio from three prior observations could robustly predict serum lithium levels (predicted vs. observed r = 0.90).

Conclusions: These findings strongly suggest that saliva could be used for lithium monitoring, and open the door for the development and implementation of a point-of-care salivary lithium device for use at home or the clinic. We propose that the use of saliva will dramatically improve treatment opportunities for patients with mood disorders.
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http://dx.doi.org/10.1111/bdi.13128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291088PMC
November 2021

Health reference intervals and values for common bottlenose dolphins (Tursiops truncatus), Indo-Pacific bottlenose dolphins (Tursiops aduncus), Pacific white-sided dolphins (Lagenorhynchus obliquidens), and beluga whales (Delphinapterus leucas).

PLoS One 2021 30;16(8):e0250332. Epub 2021 Aug 30.

Conservation Science and Animal Welfare Research, Chicago Zoological Society-Brookfield Zoo, Brookfield, IL, United States of America.

This study reports comprehensive clinical pathology data for hematology, serum, and plasma biochemistry reference intervals for 174 apparently healthy common bottlenose dolphins (Tursiops truncatus) and reference values for 27 Indo-Pacific bottlenose dolphins (Tursiops aduncus), 13 beluga whales (Delphinapterus leucas), and 6 Pacific white-sided dolphins (Lagenorhynchus obliquidens) in zoos and aquariums accredited by the Alliance for Marine Mammal Parks and Aquariums and the Association of Zoos & Aquariums. Blood samples were collected as part of a larger study titled "Towards understanding the welfare of cetaceans in zoos and aquariums" (colloquially called the Cetacean Welfare Study). Two blood samples were collected following a standardized protocol, and two veterinarian examinations were conducted approximately six months apart between July to November 2018 and January to April 2019. Least square means, standard deviations, and 95% confidence intervals were calculated for hematology, serum, and plasma biochemical variables. Comparisons by age, gender, and month revealed statistically significant differences (p < 0.01) for several variables. Reference intervals and values were generated for samples tested at two laboratories for up to 56 hematologic, serum, and plasma biochemical variables. To apply these data, ZooPhysioTrak, an iOS mobile software application, was developed to provide a new resource for cetacean management. ZooPhysioTrak provides species-specific reference intervals and values based on user inputs of individual demographic and sample information. These data provide a baseline from which to compare hematological, serum, and plasma biochemical values in cetaceans in zoos and aquariums.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250332PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405036PMC
November 2021

Reference intervals and values for fecal cortisol, aldosterone, and the ratio of cortisol to dehydroepiandrosterone metabolites in four species of cetaceans.

PLoS One 2021 30;16(8):e0250331. Epub 2021 Aug 30.

Biology Department, Portland State University, Portland, OR, United States of America.

The goal of the current study was to create reference intervals and values for several common and one potential novel physiological indicators of animal welfare for four species of cetaceans. The subjects included 189 bottlenose dolphins (Tursiops truncatus), 27 Indo-Pacific bottlenose dolphins (Tursiops aduncus), eight Pacific white-sided dolphins (Lagenorhynchus obliquidens), and 13 beluga whales (Delphinapterus leucas) at Alliance of Marine Mammal Parks and Aquariums and/or Association of Zoos and Aquariums accredited facilities. During two sampling time periods between July and November of 2018 and between January and April of 2019, fecal samples were collected weekly for five weeks from all animals. Samples were processed and analyzed using enzyme immunoassay for fecal cortisol, aldosterone, and dehydroepiandrosterone (DHEA) metabolites. Linear mixed models were used to examine demographic and time factors impacting hormone metabolite concentrations. Age, sex, and time of year were all significant predictors for some of the models (p < 0.01). An iOS mobile application ZooPhysioTrak was created for easy access to species-specific reference intervals and values accounting for significant predictors. For facilities without access to this application, additional reference intervals and values were constructed without accounting for significant predictors. Information gained from this study and the use of the application can provide reference intervals and values to make informed management decisions for cetaceans in zoological facilities.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250331PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404979PMC
November 2021

Bottlenose dolphin habitat and management factors related to activity and distance traveled in zoos and aquariums.

PLoS One 2021 30;16(8):e0250687. Epub 2021 Aug 30.

Conservation Science and Animal Welfare Research, Chicago Zoological Society - Brookfield Zoo, Brookfield, Illinois, United States of America.

High-resolution non-invasive cetacean tagging systems can be used to investigate the influence of habitat characteristics and management factors on behavior by quantifying activity levels and distance traveled by bottlenose dolphins (Tursiops truncatus and Tursiops aduncus) in accredited zoos and aquariums. Movement Tags (MTags), a bio-logging device, were used to record a suite of kinematic and environmental information outside of formal training sessions as part of a larger study titled "Towards understanding the welfare of cetaceans in zoos and aquariums" (colloquially called the Cetacean Welfare Study). The purpose of the present study was to explore if and how habitat characteristics, environmental enrichment programs, and training programs were related to the distance traveled and energy expenditure of dolphins in accredited zoos and aquariums. Bottlenose dolphins in accredited zoos and aquariums wore MTags one day per week for two five-week data collection periods. Overall dynamic body acceleration (ODBA), a proxy for energy expenditure, and average distance traveled per hour (ADT) of 60 dolphins in 31 habitats were examined in relation to demographic, habitat, and management factors. Participating facilities were accredited by the Alliance for Marine Mammal Parks and/or Aquariums and the Association of Zoos & Aquariums. Two factors were found to be related to ADT while six factors were associated with ODBA. The results showed that enrichment programs were strongly related to both ODBA and ADT. Scheduling predictable training session times was also positively associated with ADT. The findings suggested that habitat characteristics had a relatively weak association with ODBA and were not related to ADT. In combination, the results suggested that management practices were more strongly related to activity levels than habitat characteristics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250687PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405030PMC
November 2021

Towards understanding the welfare of cetaceans in accredited zoos and aquariums.

PLoS One 2021 30;16(8):e0255506. Epub 2021 Aug 30.

Conservation Science and Animal Welfare Research, Chicago Zoological Society - Brookfield Zoo, Brookfield, Illinois, United States of America.

Cetaceans are long-lived, social species that are valued as ambassadors inspiring the public to engage in conservation action. Under professional care, they are critical partners with the scientific community to understanding the biology, behavior, physiology, health, and welfare requirements of this taxonomic group. The Cetacean Welfare Study was a highly collaborative research effort among zoos and aquariums accredited by the Alliance for Marine Mammal Parks and Aquariums and/or the Association of Zoos & Aquariums that provided important empirical and comparative information on the care and management of cetaceans. The goal was to identify factors that were related to the welfare of bottlenose dolphins and to develop reference intervals and values for common and novel indicators of health and welfare for common bottlenose dolphins (Tursiops truncatus), Indo-Pacific bottlenose dolphins (Tursiops aduncus), beluga whales (Delphinapterus leucas), and Pacific white-sided dolphins (Lagenorhynchus obliquidens). Data were collected from cetaceans at 43 accredited zoos and aquariums in seven countries in 2018 and 2019. This overview presents a summary of findings from the initial research articles that resulted from the study titled "Towards understanding the welfare of cetaceans in zoos and aquariums." With multiple related objectives, animal-based metrics were used to advance frameworks of clinical care and target key conditions that were associated with good welfare of cetaceans in zoo and aquarium environments. As a result of this collaboration, species-specific reference intervals and values for blood variables and fecal hormone metabolites were developed and are freely available in an iOS application called ZooPhysioTrak. The results suggested that environmental enrichment programs and social management factors were more strongly related to behaviors likely indicative of positive welfare than habitat characteristics for common and Indo-Pacific bottlenose dolphins. These findings can be widely applied to optimize care and future science-based welfare practice.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255506PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404978PMC
November 2021

Relationships between animal management and habitat characteristics with two potential indicators of welfare for bottlenose dolphins under professional care.

PLoS One 2021 30;16(8):e0252861. Epub 2021 Aug 30.

Institute for interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, United States of America.

Accredited zoos and aquariums continually strive to ensure high levels of animal welfare for the animals under their professional care. Best management practices include conducting research to better understand factors that lead to optimal welfare and then turning findings into practice. The current study is part of the larger Cetacean Welfare Study or more formally, "Towards understanding the welfare of cetaceans in zoos and aquariums." Facilities participating in the study were accredited by the Alliance of Marine Mammal Parks and Aquariums and/or the Association of Zoos and Aquariums. Animal management factors and habitat characteristics were examined in relation to two potential indicators of welfare for common (Tursiops truncatus) and Indo-Pacific (Tursiops aduncus) bottlenose dolphins. Specifically, we examined environmental enrichment, animal training, and habitat characteristics that were significantly related to behavioral diversity and route tracing, a form of stereotypic behavior. Behavior was recorded from 47 animals at 25 facilities around the world. Overall, the rate of route tracing behavior observed during the study was very low and few animal management factors or habitat characteristics were found to be related to this behavior. One factor, enrichment diversity, had a significant positive relationship with route tracing and an inverse relationship with behavioral diversity. This finding may be a product of a response mounted by animal care specialists to the behavior as opposed to a cause. Animals that engaged in this behavior were likely provided more diverse enrichment in attempts to ameliorate the stereotypic behavior. However, multiple factors were found to significantly relate to behavioral diversity, a potential positive indicator of welfare for bottlenose dolphins. Dolphins that were trained on a predictable schedule had higher behavioral diversity than those on a semi-predictable schedule. There was a positive significant relationship between behavioral diversity and the number of habitats to which an animal had access, and a significant inverse relationship with the maximum depth of the habitat. Finally, animals that were split into groups and reunited or rotated between subgroups had higher behavioral diversity than animals managed in the same group. Information gained from the current study suggested that animal management techniques may be more important in ensuring good welfare for bottlenose dolphins than focusing on habitat size.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252861PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405007PMC
November 2021

Assessment of animal management and habitat characteristics associated with social behavior in bottlenose dolphins across zoological facilities.

PLoS One 2021 30;16(8):e0253732. Epub 2021 Aug 30.

Institute for interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, United States of America.

Bottlenose dolphins are a behaviorally complex, social species that display a variety of social behaviors. Because of this, it is important for zoological facilities to strive to ensure animals display species-appropriate levels of social behavior. The current study is part of the multi-institutional study entitled "Towards understanding the welfare of cetaceans in zoos and aquariums" commonly referred to as the Cetacean Welfare Study. All participating facilities were accredited by the Alliance of Marine Mammal Parks and Aquariums and/or the Association of Zoos and Aquariums. Behavioral data were collected on 47 bottlenose dolphins representing two subspecies, Tursiops truncatus and Tursiops aduncus, at 25 facilities. The social behaviors of group related activity (group active) as well as interacting with conspecifics (interact with conspecific) were examined for their relationships to both animal management factors and habitat characteristics. The behavioral state of group active and the rate of interact with conspecific were both positively related to the frequency of receiving new forms of environmental enrichment. Both were inversely related to the random scheduling of environmental enrichment. Additional results suggested interact with conspecific was inversely related with daytime spatial experience and that males displayed group active more than females. Overall, the results suggested that animal management techniques such as the type and timing of enrichment may be more important to enhance social behavior than habitat characteristics or the size of the habitat. Information gained from this study can help facilities with bottlenose dolphins manage their enrichment programs in relation to social behaviors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253732PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405028PMC
November 2021

Behavioral diversity as a potential positive indicator of animal welfare in bottlenose dolphins.

PLoS One 2021 30;16(8):e0253113. Epub 2021 Aug 30.

Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, California, United States of America.

Accredited zoological facilities are committed to fully understanding the behavioral, mental, and physical needs of each species to continuously improve the welfare of the animals under their professional care and detect when welfare has diminished. In order to accomplish this goal, internally consistent and externally valid indicators of animal welfare are necessary to advance our understanding of the current welfare status of individual animals. Historically, efforts have focused on monitoring visible or observable signs of poor health or problem behavior, but lack of signs or problems does not necessarily demonstrate that an individual animal is thriving. The current study examined fecal hormone metabolite levels and behavior for two species of bottlenose dolphins (Tursiops truncatus and Tursiops aduncus) from 25 different accredited zoological facilities. At the time of the study, all facilities were accredited by the Alliance of Marine Mammal Parks and Aquariums and/or the Association of Zoos and Aquariums. This was part of the multi-institutional study 'Towards understanding of the welfare of cetaceans in zoos and aquariums" commonly referred to as the Cetacean Welfare Study. Behavioral diversity was calculated using the Shannon Diversity Index on species-appropriate behavioral events. Behavioral diversity was compared to the fecal metabolites of cortisol, aldosterone, and the ratio of cortisol to dehydroepiandrosterone (DHEA) as well as the stereotypic behavior of route tracing. Similar to previous studies on other species, there was a significant inverse relationship between behavioral diversity and both fecal cortisol metabolites and route tracing. Additionally, a significant inverse relationship also exists between behavioral diversity and the ratio of fecal cortisol to DHEA metabolites. Behavioral diversity and fecal aldosterone metabolites were not associated. Additional research is still needed to validate behavioral diversity as an indicator of positive animal welfare for bottlenose dolphins and across species. However, based on current results, facilities could utilize behavioral diversity combined with other measures of welfare to more comprehensively evaluate the welfare of bottlenose dolphins.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253113PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405024PMC
November 2021

Habitat characteristics and animal management factors associated with habitat use by bottlenose dolphins in zoological environments.

PLoS One 2021 30;16(8):e0252010. Epub 2021 Aug 30.

Conservation Science and Animal Welfare Research, Chicago Zoological Society-Brookfield Zoo, Brookfield, IL, United States of America.

The way an animal uses its habitat can serve as an indicator of habitat appropriateness for the species and individuals. Bottlenose dolphins (Tursiops truncatus and Tursiops aduncus) in accredited zoos and aquariums experience a range of habitat types and management programs that provide opportunities for dolphins to engage in species-appropriate behaviors and potentially influence their individual and group welfare. Data in the present study were collected as part of a larger study titled "Towards understanding the welfare of cetaceans in zoos and aquariums" (colloquially called the Cetacean Welfare Study). Non-invasive bio-logging devices (Movement Tags) recorded the diving behavior and vertical habitat movements of 60 bottlenose dolphins at 31 zoos and aquariums that were accredited by the Alliance for Marine Mammal Parks and Aquariums and/or the Association of Zoos & Aquariums. Bottlenose dolphins wore a Movement Tag one day per week for two five-week data collection periods. Demographic variables, environmental enrichment programs, training programs, and habitat characteristics were associated with habitat usage. Longer dive durations and use of the bottom third of the habitat were associated with higher enrichment program index values. Dolphins receiving new enrichment on a monthly/weekly schedule also used the bottom third of the habitat more often than those receiving new enrichment on a yearly/year+ schedule. Dolphins that were managed in a group that was split into smaller subgroups during the day and were reunited into one group at night spent less time in the top third of the habitat than those who remained in a single group with consistent members at all times. Dolphins that were managed as subgroups with rotating members but were never united as one group spent less time in the bottom third of the habitat than those who remained in a single group with consistent members at all times. Taken together, the results suggested that management practices, such as enrichment and training programs, played a greater role in how dolphins interacted with their environment relative to the physical characteristics of the habitat.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252010PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404980PMC
November 2021

Environmental enrichment, training, and habitat characteristics of common bottlenose dolphins (Tursiops truncatus) and Indo-Pacific bottlenose dolphins (Tursiops aduncus).

PLoS One 2021 30;16(8):e0253688. Epub 2021 Aug 30.

Conservation Science and Animal Welfare Research, Chicago Zoological Society - Brookfield Zoo, Brookfield, Illinois, United States of America.

In recent decades, animal welfare science has evolved to utilize a multidisciplinary approach to assess the welfare of animals in accredited zoos and aquariums. Science-based animal welfare assessments have become an essential component of management programs and widespread application is expected by animal care professionals. Management practices for bottlenose dolphins in accredited facilities incorporate several programs that potentially impact animal welfare including environmental enrichment and animal training. Additionally, habitat characteristics, such as the dimensions of the habitat, have been proposed to affect welfare. While accredited facilities are required to meet high standards of care, habitat characteristics and management practices are not standardized across locations. Knowledge and subsequent application of these practices and habitat characteristics can enhance our understanding of factors associated with positive welfare. As part of a larger study of dolphin welfare titled "Towards understanding the welfare of cetaceans in zoos and aquariums" (colloquially called the Cetacean Welfare Study), survey data were collected from 86 bottlenose dolphins in 40 habitats at 38 facilities in seven countries. The major aims of this paper are to provide general descriptive information regarding dolphin management in accredited zoos and aquariums and to provide supplemental context to the other research published from the Cetacean Welfare Study data set. This paper provides a review of current habitat characteristics and management practices at those 38 accredited zoos and aquariums. These data enabled the identification and quantification of how cetacean management practices differed between participating facilities accredited by the Alliance for Marine Mammal Parks and Aquariums and the Association of Zoos & Aquariums. Variables were selected based on their potential association with welfare including the physical habitat, environmental enrichment, and training programs. The variables were also used for subsequent research in this collection of related papers to investigate important connections between potential indicators of welfare and habitat characteristics, environmental enrichment, and training programs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253688PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404999PMC
November 2021

The biobehavioral impacts of sexual violence: Findings from an acute repeat survivor of vaginal rape.

Womens Health (Lond) 2021 Jan-Dec;17:17455065211031079

Division of Infectious Diseases and Global Public Health, Department of Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, USA.

Background: Individuals who have experienced repeat sexual violence victimization face adverse mental and physical health outcomes, including immune and stress response functioning. We aim to further understand repeat sexual violence victimization to develop responsive and appropriate treatment for survivors of sexual violence.

Methods: We present the immunological and contextual findings of a participant ( = 1) who experienced repeat sexual violence victimization during her enrollment in The THRIVE Study, a prospective case-control study of women aged 14-45 years, who have experienced recent consensual vaginal penetration ("controls") or forced vaginal penetration ("cases"). Participants complete a survey, HIV/sexually transmitted infection, and pregnancy testing, blood sampling for C-reactive protein and adrenocorticotrophic hormone, collection of cervicovaginal fluid for immunological biomarkers, and self-collection of saliva samples for cortisol measurements, across study visits (Baseline, 1, and 3 months).

Results: The case study participant, aged 18 years upon enrollment, experienced sexual trauma before four of five study visits. Trends in the mental health indicators demonstrate reciprocal fluctuations in adverse mental health and resilience in accordance with revictimization and circumstantial changes. Suppressed immune biomarkers appear to correlate with increased adverse mental health, while mental health recovery trends with immunological recovery. The participant presents with dysregulated hypothalamic-pituitary-adrenal axis diurnal profile.

Conclusions: This profile illustrates the intra-individual biobehavioral impact of experience with revictimization over the course of 6 months, capturing experiences that are rarely studied either longitudinally or with the depth of the current research. The findings underscore the value of monitoring cervicovaginal immune functioning and hypothalamic-pituitary-adrenal axis dysregulation in coordination with changes in mental health over the course of repeated sexual trauma.
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http://dx.doi.org/10.1177/17455065211031079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280840PMC
October 2021

Censored data considerations and analytical approaches for salivary bioscience data.

Psychoneuroendocrinology 2021 07 17;129:105274. Epub 2021 May 17.

Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, USA; Department of Psychological Science, University of California, Irvine, CA, USA. Electronic address:

Left censoring in salivary bioscience data occurs when salivary analyte determinations fall below the lower limit of an assay's measurement range. Conventional statistical approaches for addressing censored values (i.e., recoding as missing, substituting or extrapolating values) may introduce systematic bias. While specialized censored data statistical approaches (i.e., Maximum Likelihood Estimation, Regression on Ordered Statistics, Kaplan-Meier, and general Tobit regression) are available, these methods are rarely implemented in biobehavioral studies that examine salivary biomeasures, and their application to salivary data analysis may be hindered by their sensitivity to skewed data distributions, outliers, and sample size. This study compares descriptive statistics, correlation coefficients, and regression parameter estimates generated via conventional and specialized censored data approaches using salivary C-reactive protein data. We assess differences in statistical estimates across approach and across two levels of censoring (9% and 15%) and examine the sensitivity of our results to sample size. Overall, findings were similar across conventional and censored data approaches, but the implementation of specialized censored data approaches was more efficient (i.e., required little manipulations to the raw analyte data) and appropriate. Based on our review of the findings, we outline preliminary recommendations to enable investigators to more efficiently and effectively reduce statistical bias when working with left-censored salivary biomeasure data.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260151PMC
July 2021

DNA methylation in former extremely low birth weight newborns: association with cardiovascular and endocrine function.

Pediatr Res 2022 05 5;91(6):1469-1477. Epub 2021 May 5.

University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Background: There is increased risk of cardiovascular, metabolic, and hypertensive disorders in later life in the preterm population. We studied school-age children who had been born extremely premature who had undergone endocrine, cardiovascular, and anthropometric evaluations.

Methods: School age measurements of salivary cortisol, adrenal androgens, blood pressure, and anthropometric markers were correlated with DNA methylation of 11-betahydroxysteroid dehydrogenase type 2 (11BHSD2), leptin, and the LINE1 repetitive DNA element.

Results: We observed a modest correlation between log AUC for salivary cortisol and methylation of leptin in preterm infants and a negative correlation between methylation of region 1 of the glucocorticoid receptor (GR in term-born infants. There was an association between LINE1 methylation and cortisol response to awakening and a negative correlation between LINE1 and systolic blood pressure at 6-7 years. Methylation of the GR promoter region showed a positive association with systolic blood pressure at 6-7 years of age.

Conclusions: These results show that extremely preterm birth, followed by complex patterns of endocrine, cardiovascular, and metabolic exposures during early postnatal life, is associated with lasting changes in DNA methylation patterns in genes involved in hypothalamic pituitary adrenal axis function, adrenal hormonal regulation, and cardiometabolic risk.

Impact: Preterm infants have significant environmental and physiological exposures during early life that may have lasting impact on later function. Alterations in hypothalamic pituitary adrenal axis (HPA) function have been associated with these exposures. We examined the associated changes in DNA methylation of important genes involved in HPA function, metabolism, and global DNA methylation. The changes we saw in DNA methylation may help to explain associated cardiovascular, metabolic, and growth disturbance in these children in later life.
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http://dx.doi.org/10.1038/s41390-021-01531-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8568736PMC
May 2022

The case for the repeatability intra-class correlation as a metric of precision for salivary bioscience data: Justification, assessment, application, and implications.

Psychoneuroendocrinology 2021 06 17;128:105203. Epub 2021 Mar 17.

Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, USA; Department of Psychological Science, University of California, Irvine, CA, USA; Department of Acute and Chronic Care, Johns Hopkins University School of Nursing, Baltimore, MD, USA; Department of Pediatrics Johns Hopkins University School of Medicine, Baltimore, MD, USA; Salivary Bioscience Laboratory and Department of Psychology, University of Nebraska, Lincoln, NE, USA.

Best practice standards for measuring analyte levels in saliva recommend that all biospecimens be tested in replicate with mean concentrations used in statistical analyses. This approach prioritizes minimizing laboratory-based measurement error but, in the process, expends considerable resources. We explore the possibility that, due to advances in salivary assay precision, the contribution of laboratory-based measurement error in salivary analyte data is very small relative to more important and meaningful variability in analyte levels across biological replicates (i.e., between different specimens). To evaluate this possibility, we examine the utility of the repeatability intra-class correlation (rICC) as an additional index of salivary analyte data precision. Using randomly selected subsamples (Ns=200 and 60) of salivary analyte data collected as part of a larger epidemiologic study, we compute the rICCs for seven commonly assayed salivary measures in biobehavioral research - cortisol, alpha-amylase, c-reactive protein, interlekin-6, uric acid, secretory immunoglobulin A, and testosterone. We assess the sensitivity of rICC estimates to assay type and the unique distributions of the underlying analyte data. We also use simulations to examine the bias, precision, and coverage probability of rICC estimates calculated for small to large sample sizes. For each analyte, the rICCs revealed that less than 5% of variation in analyte levels was attributable to laboratory-based measurement error. rICC estimates were similar across all analytes despite differences in analyte levels, average intra-assay coefficients of variation, and in the distributional properties of the data. Guidelines for calculating rICC are provided to enable investigators and laboratory staff to apply this metric and more accurately quantify, and communicate, the magnitude of laboratory-based measurement error in their data. By helping investigators scale measurement error relative to more scientifically meaningful variability between biological replicates, the application of the rICC has the potential to influence research strategies and tactics such that resources (e.g., finances, effort, number/volume of biospecimens) are allocated more efficiently and effectively.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136357PMC
June 2021

Correspondence Between Perceived Pubertal Development and Hormone Levels in 9-10 Year-Olds From the Adolescent Brain Cognitive Development Study.

Front Endocrinol (Lausanne) 2020 18;11:549928. Epub 2021 Feb 18.

Department of Pediatrics, University of Minnesota, Minneapolis, MN, United States.

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.

Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.

Results: PDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.

Conclusions: Sociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.
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http://dx.doi.org/10.3389/fendo.2020.549928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930488PMC
May 2021

Residential Greenness Positively Associated with the Cortisol to DHEA Ratio among Urban-Dwelling African American Women at Risk for HIV.

J Urban Health 2021 08 9;98(4):570-578. Epub 2020 Nov 9.

, La Jolla, USA.

As ecosystems that support human health, societies, and civilization change in the era of the Anthropocene, individuals with disproportionate balance of salivary hormones may be at greatest risk of morbidity and mortality. Vulnerable communities, in particular, are overburdened by inequities in features of built environments linked to health disparities. This study examined the cross-sectional association of greenness in the built environment with the ratio of cortisol to dehydroepiandrosterone (DHEA) in an urban-dwelling high-risk community sample of African American women (n = 84, age 18-44 years). Saliva samples, collected across 2 consecutive days, were assayed for cortisol and DHEA. Controlling for sexual violence, perceived stress, education, and income, as well as crime, traffic density, and vacant properties, we observed a significant positive cross-sectional association between greenness and the cortisol to DHEA ratio, (β = 7·5, 95% CI: 0.89, 14.19). The findings highlight environmental influence on stress response at waking when there is the greatest individual variation. Implications for advancing our understanding of the waking ratio of cortisol to DHEA as a potential marker of physiological resilience are discussed.
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http://dx.doi.org/10.1007/s11524-020-00492-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382813PMC
August 2021

COVID-19 Serology at Population Scale: SARS-CoV-2-Specific Antibody Responses in Saliva.

J Clin Microbiol 2020 12 17;59(1). Epub 2020 Dec 17.

Department of Environmental Health and Engineering, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses ( = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing.
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http://dx.doi.org/10.1128/JCM.02204-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771435PMC
December 2020

Correspondence Between Cytomegalovirus Immunoglobulin-G Levels Measured in Saliva and Serum.

Front Immunol 2020 28;11:2095. Epub 2020 Aug 28.

Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, Irvine, CA, United States.

Human cytomegalovirus (HCMV) infects more than 80% of the global population. While mostly asymptomatic, HCMV infection can be serious among the immunocompromised, and it is implicated in chronic disease pathophysiology in adulthood. Large-scale minimally invasive HCMV screening could advance research and public health efforts to monitor infection prevalence and prevent or mitigate downstream risks associated with infection. We examine the utility of measuring HCMV immunoglobulin-G (IgG) levels in saliva as an index of serum levels. Matched serum and saliva samples from healthy adults ( = 98; 44% female; 51% white) were assayed for HCMV IgG, total salivary protein, and salivary markers related to oral inflammation, blood, and tissue integrity. We examine the serum-saliva association for HCMV IgG and assess the influence of participant characteristics and factors specific to the oral compartment (e.g., oral inflammation) on HCMV IgG levels and cross-specimen relations. We found a robust serum-saliva association for HCMV IgG with serum antibody levels accounting for >60% of the variance in salivary levels. This relation remained after adjusting for key demographic and oral immune-related variables. Compared to the serum test, the salivary HCMV IgG test had 51% sensitivity and 97% specificity. With improvements in assay performance and sample optimization, HCMV antibody levels in oral fluids may be a useful proxy for serum levels.
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http://dx.doi.org/10.3389/fimmu.2020.02095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484902PMC
April 2021

Best practice recommendations for the measurement and interpretation of salivary proinflammatory cytokines in biobehavioral research.

Brain Behav Immun 2021 01 12;91:105-116. Epub 2020 Sep 12.

Institute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, USA; Department of Psychological Science, University of California, Irvine, CA, USA; Department of Acute and Chronic Care, Johns Hopkins University School of Nursing, Baltimore, MD, USA; Department of Pediatrics Johns Hopkins University School of Medicine, Baltimore, MD, USA; Salivary Bioscience Laboratory and Department of Psychology, University of Nebraska, Lincoln, NE, USA.

Despite the integration of salivary inflammatory cytokines into research across the biobehavioral, psychological, clinical, and health-related disciplines, there is little guidance regarding the biospecimen collection, handling, and storage practices that maximize the quality and validity of salivary cytokine data. Furthermore, associations between salivary cytokines and measures related to oral health are rarely assessed and accounted for in studies outside the oral health fields. To address these gaps, we examine the sensitivity of salivary interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) to changes in saliva sample collection technique and cold chain management procedures. Using subsets of saliva samples collected from 150 healthy adults, we measure salivary IL-1β, IL-6, IL-8, TNF-α, and other oral health-related indices (i.e., blood contamination [transferrin], and salivary matrixmallotprotienase-8). In addition to examining changes in cytokine levels associated with sample collection technique and cold chain management procedures, we assess relations between cytokine concentrations and levels of other oral health-related measures. We found that IL-1β, IL-6, and IL-8 were more robust to changes in sample collection and cold chain management procedures than TNF-α, and all cytokines were positively associated with other oral health-related measures. Based on our findings, we recommend analyte-specific guidance for measuring and interpreting salivary cytokine concentrations.
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http://dx.doi.org/10.1016/j.bbi.2020.09.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164445PMC
January 2021

The Role of Stress and Genital Immunity in Sexual Trauma and HIV Susceptibility Among Adolescent Girls and Adult Women (The THRIVE Study): Protocol for a Longitudinal Case-Control Study.

JMIR Res Protoc 2020 Dec 7;9(12):e18190. Epub 2020 Dec 7.

Department of Epidemiology, Milken Institute School of Public Health, The George Washington University, Washington, DC, United States.

Background: The relationship between sexual violence and HIV risk has been extensively documented through social and behavioral research; however, the underlying biological mechanisms are poorly understood.

Objective: The purpose of the THRIVE (Trauma and HIV Risk: Investigating Stress and the Immune Disruption of the Vaginal Environment) Study is to examine the impact of sexual trauma due to sexual violence on HIV susceptibility through dysregulation of soluble inflammatory and anti-inflammatory and anti-HIV biomarkers in the female genital tract and dysregulation of the hypothalamic-pituitary-adrenal axis among adolescent girls and adult women.

Methods: The THRIVE Study is a longitudinal case-control study conducted in San Diego, CA, among a racially diverse sample. Cases are adolescent girls (aged 14-19 years) or adult women (aged 20-45 years) who have experienced forced vaginal penetration by a phallus perpetrated by a man within the past 15 days. Controls are adolescent girls or adult women who have engaged in consensual vaginal sex with a man within the past 15 days. At baseline and 1- and 3-month follow-up study visits, participants undergo a urine-based pregnancy test; venipuncture blood draw for HIV, C-reactive protein, adrenocorticotropic hormone, and progesterone testing; a 45-min interviewer-administered computer survey; and cervicovaginal lavage to measure proinflammatory and anti-inflammatory and anti-HIV soluble immune biomarkers. After each study visit, participants self-collect saliva specimens (upon waking, 30 min after waking, and 45 min after waking) at home for 3 consecutive days, which are later assayed for cortisol and dehydroepiandrosterone sulfate. Participants receive compensation at each study visit and for the return of saliva specimens, and a list of local medical and support services. Study procedures use trauma-informed care methods, given the sensitive nature of the study and enrollment of women in the acute phase after sexual trauma. All research staff and investigators adhere to ethical principles and guidelines in the conduct of research activities. Data will be analyzed for descriptive and inferential analyses.

Results: The recruitment of participants is ongoing. The publication of the first results is expected by late 2021.

Conclusions: The THRIVE Study will provide foundational knowledge on how sexual trauma due to sexual violence increases susceptibility to HIV acquisition via alterations in cervicovaginal immune regulation and the psychobiology of the stress responses. These findings will inform future research on mechanistic models of in vitro and in vivo injury and cervicovaginal wound healing processes, which may lead to the development of nonvaccine biomedical HIV prevention products for girls and women.

International Registered Report Identifier (irrid): DERR1-10.2196/18190.
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http://dx.doi.org/10.2196/18190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752525PMC
December 2020

Levels of Interleukin-6 in Saliva, but Not Plasma, Correlate with Clinical Metrics in Huntington's Disease Patients and Healthy Control Subjects.

Int J Mol Sci 2020 Sep 2;21(17). Epub 2020 Sep 2.

Institute for Interdisciplinary Salivary Bioscience Research, University of California Irvine, Irvine, CA 92697, USA.

Growing evidence suggests that inflammatory responses, in both the brain and peripheral tissues, contribute to disease pathology in Huntington's disease (HD), an inherited, progressive neurodegenerative disorder typically affecting adults in their 30-40 s. Hence, studies of inflammation-related markers in peripheral fluids might be useful to better characterize disease features. In this study, we measured levels of C-reactive protein (CRP), Interleukin-6 (IL-6), interleukin 1 beta (IL-1B), and alpha-amylase (AA) in saliva and plasma from = 125 subjects, including = 37 manifest HD patients, = 36 premanifest patients, and = 52 healthy controls, using immunoassays. We found increases in salivary levels of IL-6, IL-1B and CRP across different disease groups and increased levels of IL-6 in the plasma of HD patients as compared to premanifest patients and controls. The levels of salivary IL-6 were significantly correlated with each of the other salivary markers, as well as with IL-6 levels measured in plasma. Further, salivary IL-6 and IL-1B levels were significantly positively correlated with Total Motor Score (TMS) and chorea scores and negatively correlated with Total Functional Capacity (TFC) in HD patients, whereby in healthy control subjects, IL-6 was significantly negatively correlated with Montreal Cognitive Assessment (MoCA) and the Symbol Digit Modalities test (SDM). Interestingly, the plasma levels of IL-6 did not show similar correlations to any clinical measures in either HD or control subjects. These findings suggest that salivary IL-6 is particularly relevant as a potential non-invasive biomarker for HD symptoms. The advent of an effective, dependable salivary biomarker would meet the urgent need for a less invasive means of identifying and monitoring HD disease progression.
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http://dx.doi.org/10.3390/ijms21176363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503233PMC
September 2020
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