Young children who experience toxic stress are at high risk for a number of health outcomes in adulthood, including cardiovascular disease, cancers, asthma, and depression. The American Academy of ...Pediatrics has recently called on pediatricians, informed by research from molecular biology, genomics, immunology, and neuroscience, to become leaders in science-based strategies to build strong foundations for children's life-long health. In this report, we provide an overview of the science of toxic stress. We summarize the development of the neuroendocrine-immune network, how its function is altered by early life adversity, and how these alterations then increase vulnerability to disease. The fact that early environments shape and calibrate the functioning of biological systems very early in life is both a cautionary tale about overlooking critical periods in development and reason for optimism about the promise of intervention. Even in the most extreme cases of adversity, well-timed changes to children's environments can improve outcomes. Pediatricians are in a unique position to contribute to the public discourse on health and social welfare by explaining how factors that seem distal to child health may be the key to some of the most intractable public health problems of our generation. We consider the challenges and opportunities for preventing toxic stress in the context of contemporary pediatric practice.
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.
Perceived racial discrimination has been associated with the autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis activities-two major stress response systems. To date, most ...studies have used cross-sectional data that captured retrospective measures of the racial discrimination associated with current physiological stress responses. The purpose of this study was to examine the relationship between racial discrimination measured in real-time and physiological stress responses. Twelve healthy Black adults completed baseline surveys and self-collected saliva samples 4x/day for 4 days to measure cortisol and alpha amylase (AA) as a proxy of HPA and ANS systems, respectively. Real-time racial discrimination was measured using ecological momentary assessments (EMA) sent to participants 5x/day for 7 days. Multilevel models were conducted to examine the relationship between racial discrimination and stress responses. In multilevel models, the previous day's racial discrimination was significantly associated with the next day's cortisol level at wakening (β = 0.81, partial r = 0.74, p<0.01) and diurnal slope (β = -0.85, partial r = -0.73, p<0.01). Also, microaggressions were significantly associated with the diurnal cortisol slope in the same day, indicating that on the day when people reported more microaggressions than usual, a flatter diurnal slope of cortisol was observed (β = -0.50, partial r = -0.64, p<0.01). The concurrent use of salivary biomarkers and EMA was feasible methods to examine the temporal relationship between racial discrimination and physiological stress responses. The within-person approach may help us understand the concurrent or lagged effects of racial discrimination on the stress responses. Further studies are needed to confirm the observed findings with a large sample size and to improve stress related health outcomes in racial/ethnic minorities.
In a predominantly low-income population-based longitudinal sample of 1,292 children followed from birth, higher level of salivary cortisol assessed at ages 7, 15, and 24 months was uniquely ...associated with lower executive function ability and to a lesser extent IQ at age 3 years. Measures of positive and negative aspects of parenting and household risk were also uniquely related to both executive functions and IQ. The effect of positive parenting on executive functions was partially mediated through cortisol. Typical or resting level of cortisol was increased in African American relative to White participants. In combination with positive and negative parenting and household risk, cortisol mediated effects of income-to-need, maternal education, and African American ethnicity on child cognitive ability.
Acute physiological responses to psychosocial stressors are a potential pathway underlying racial disparities in stress-related illnesses. Uric acid (UA) is a potent antioxidant that has been linked ...to disparities in stress-related illnesses, and recent research has shown that UA is responsive to acute social stress. However, an examination of the relationships between the purinergic system and other commonly measured stress systems is lacking. Here, we measure and characterize associations of salivary uric acid (sUA) with markers of hypothalamic-pituitary-adrenal (HPA) axis activation, sympathetic-adreno-medullar (SAM) axis activation, and acute inflammation. A community sample of 103 African Americans (33 male, 70 female) completed the Trier Social Stress Test to induce social-evaluative threat. Passive drool collected before, during, and after the stressor task provided salivary reactivity measures of UA (sUA), cortisol, dehydroepiandrosterone sulfate (DHEAS), salivary alpha amylase (sAA – a surrogate marker of SAM activity) and C-reactive protein (sCRP). Multiple regressions revealed that total activation of cortisol, DHEAS, and sCRP were each positively associated with higher total activation of sUA. Additionally, DHEAS reactivity was positively associated with sUA reactivity. Relationships between HPA-axis markers and sUA were especially observed among younger and male participants. Overall, findings suggest potential coordination of stress systems with sUA in response to acute stress, which may further the contributions of biological stress processes to racial health disparities.
•Salivary uric acid responds to acute psychosocial stress•Basal cortisol, DHEAS, salivary alpha amylase, and C-reactive protein are unassociated with basal sUA•Cortisol, DHEAS, and sCRP dynamics are associated with sUA dynamics•Multisystem alignment with sUA was stronger among male and younger participants
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.
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.
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.
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.
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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