COVID-19 as a chronic stressor and the importance of individual identity: A data-driven look at academic productivity during the pandemic.

The COVID-19 pandemic impacted personal and professional life. For academics, research, teaching, and service tasks were upended and we all had to navigate the altered landscape. However, some individuals faced a disproportionate burden, particularly academics with minoritized identities or those who were early career, were caregivers, or had intersecting identities. As comparative endocrinologists, we determine how aspects of individual and species-level variation influence response to, recovery from, and resilience in the face of stressors. Here, we flip that framework and apply an integrative biological lens to the impact of the COVID-19 chronic stressor on our endocrine community. We address how the pandemic altered impact factors of academia (e.g., scholarly products) and relatedly, how factors of impact (e.g., sex, gender, race, career stage, caregiver status, etc.) altered the way in which individuals could respond. We predict the pandemic will have long-term impacts on the population dynamics, composition, and landscape of our academic ecosystem. Impact factors of research, namely journal submissions, were altered by COVID-19, and women authors saw a big dip. We discuss this broadly and then report General and Comparative Endocrinology (GCE) manuscript submission and acceptance status by gender and geographic region from 2019 to 2023. We also summarize how the pandemic impacted individuals with different axes of identity, how academic institutions have responded, compile proposed solutions, and conclude with a discussion on what we can all do to (re)build the academy in an equitable way. At GCE, the first author positions had gender parity, but men outnumbered women at the corresponding author position. Region of manuscript origin mattered for submission and acceptance rates, and women authors from Asia and the Middle East were the most heavily impacted by the pandemic. The number of manuscripts submitted dropped after year 1 of the pandemic and has not yet recovered. Thus, COVID-19 was a chronic stressor for the GCE community.

Do categorically distinct stressors alter the attention to visual food cues?

Stressor exposure affects food intake as well as the preference for high or low palatability foods, but little is known about how stressor types impact the visual attention to food images. We used eye tracking methodology in humans to determine if activation of the hypothalamus-pituitary-adrenal (HPA) axis and sympathetic nervous system is associated with changes in attention to food images as determined by measuring changes in oculomotor activity. Specifically, we tested two questions: 1) Do categorically distinct stressors alter aspects of visual attention to food images as determined by oculomotor activity (i.e., saccade latency, gaze duration, and saccade bouts)? 2) Do categorically distinct stressors differentially affect visual attention to food images of high or low palatability? A total of sixty participants were randomly divided into one of three test groups: controls, an anticipatory stressor group, or a reactive stressor group. We measured salivary cortisol and salivary alpha-amylase (sAA) before and after stressor exposure to confirm activation of the HPA axis and sympathetic nervous system, respectively. Following stressor exposure participants performed an eye-tracking test using a standardized food picture database (Food-pics). We analyzed saccade latency, gaze duration, and saccade bouts in balanced pairs of food and non-food images. Salivary cortisol was elevated by both stressors, although the elevation in salivary cortisol to the reactive stressor was driven by women only. sAA was elevated only by the anticipatory stressor. There were main effects of image type for all three eye-tracking variables, with initial saccades of shorter latency to food images and longer gaze duration and more saccade bouts with food images. Participants exposed to the reactive stressor reduced gaze duration on food images relative to controls, and this affect was not linked to palatability or salivary cortisol levels. We conclude that the reactive stressor decreased time spent looking at food, but not non-food, images. These data are partly consistent with the idea that reactive stressors reduce attention to non-critical visual signals.

Common Health Issues Encountered by Ultraendurance Ocean Rowers.

INTRODUCTION: Ocean rowing is an extreme ultraendurance sport in which athletes push themselves to their mental and physical limits while rowing across an ocean. Limited academic attention has meant health issues facing this population are poorly understood. This report provides a descriptive analysis of the injuries and illnesses encountered by ocean rowers at sea and suggests potential preventative measures. METHODS: Retrospective self-reported data were collected from ocean rowers via an online 29-question survey, classified by medical system, and totaled to produce a report of the most frequently encountered symptoms. RESULTS: Seventy-one ocean rowers, accounting for 86 ocean rowing attempts, completed the survey. Dermatologic symptoms formed 52% (n=169) of all reported issues, followed by musculoskeletal injuries (14%; n=45), mental health symptoms (11%; n=36), gastrointestinal symptoms (5%; n=16), and neurologic symptoms (2%). Gluteal pressure sores were the most common dermatologic symptoms (24%; n=40), hallucinations the most common mental health symptoms (69%; n=25), hand and finger issues the most reported musculoskeletal problems (36%; n=16); vomiting (38%) and headaches (50%) were the most common gastrointestinal and neurologic issues, respectively. Seasickness was reported in 42% of expeditions (n=33). CONCLUSIONS: This report presents the physiological, mental, and medical challenges facing ocean rowers. Dermatologic and musculoskeletal issues were most common and varied greatly in severity. Over 90% of reported infections occurred as a dermatologic complaint, demonstrating the importance of preventative measures such as hygiene and wound care. Continued work with a larger population is required to further understand the physiological stress and medical complaints associated with transoceanic rowing.

Tectal CRFR1 receptor involvement in avoidance and approach behaviors in the South African clawed frog, Xenopus laevis.

Animals in the wild must balance food intake with vigilance for predators in order to survive. The optic tectum plays an important role in the integration of external (predators) and internal (energy status) cues related to predator defense and prey capture. However, the role of neuromodulators involved in tectal sensorimotor processing is poorly studied. Recently we showed that tectal CRFR1 receptor activation decreases food intake in the South African clawed frog, Xenopus laevis, suggesting that CRF may modulate food intake/predator avoidance tradeoffs. Here we use a behavioral assay modeling food intake and predator avoidance to test the role of CRFR1 receptors and energy status in this tradeoff. We tested the predictions that 1) administering the CRFR1 antagonist NBI-27914 via the optic tecta will increase food intake and feeding-related behaviors in the presence of a predator, and 2) that prior food deprivation, which lowers tectal CRF content, will increase food intake and feeding-related behaviors in the presence of a predator. Pre-treatment with NBI-27914 did not prevent predator-induced reductions in food intake. Predator exposure altered feeding-related behaviors in a predictable manner. Pretreatment with NBI-27914 reduced the response of certain behaviors to a predator but also altered behaviors irrelevant of predator presence. Although 1-wk of food deprivation altered some non-feeding behaviors related to energy conservation strategy, food intake in the presence of a predator was not altered by prior food deprivation. Collectively, our data support a role for tectal CRFR1 in modulating discrete behavioral responses during predator avoidance/foraging tradeoffs.

The plus maze and scototaxis test are not valid behavioral assays for anxiety assessment in the South African clawed frog.

There are no behavioral models for testing anxiety in amphibians, a group of animals widely used for developmental, ecotoxicological, and genetic research. We aimed to validate two common rodent paradigms, the plus maze and the scototaxis test, for use in the aquatic African clawed frog (Xenopus laevis). We predicted: (a) that frogs would prefer the dark, vs. light, portions of the testing arenas (face validity), (b) that this behavior could be altered with acute administration of anxio-selective drugs (construct validity), and (c) that time spent in the dark portions of the arenas would be positively correlated (predictive validity). Prior to testing, frogs were treated with fluoxetine (selective serotonin reuptake inhibitor [SSRI]), desipramine (serotonin- and norepinephrine-reuptake inhibitor), caffeine (methylxanthine, adenosine receptor antagonist, phosphodiesterase inhibitor), saline, or were left unmanipulated. Each drug was administered acutely (1 h prior to testing; caffeine) or subacutely (24, 3, and 1 h prior to testing; fluoxetine, desipramine) at one of three doses. Plus maze and scototaxis testing were separated by 1 week; each frog completed both behavioral tasks and was treated with the same drug regimen prior to testing. Overall, both tests showed face validity, however, data suggest these paradigms lack both construct and predictive validity.

Neuroendocrine modulation of predator avoidance/prey capture tradeoffs: Role of tectal NPY2R receptors.

The optic tectum rapidly inhibits food intake when a visual threat is present. Anatomical and electrophysiological evidence support a role for neuropeptide Y (NPY), originating from cells in the thalamus, in the tectal inhibition of prey capture. Here we test the hypothesis that tectal NPY receptor type 2 (NPY2R) influences prey-capture and predator-avoidance responses in the African clawed frog, Xenopus laevis. We tested two questions: 1) Does tectal NPY administration decrease food intake and alter prey-capture behavior? 2) Does tectal administration of a NPY2R antagonist increase food intake, alter prey-capture behavior, and alter predator avoidance behavior? NPY microinjected bilaterally into the tecta failed to significantly alter food intake at any dose tested, although predator presence significantly reduced food intake. However, NPY differentially altered discrete components of prey capture including increasing the latency to contact food and reducing the amount of time in contact with food. These effects were blocked by the NPY2R antagonist BIIE0246. Additionally, BIIE0246 elevated food intake on its own after bilateral tectal microinjection. Furthermore, BIIE0246 reversed the reduction of food intake caused by exposure to a predator. Overall, these findings indicate that tectal NPY2R activation causes frogs to consume food more quickly, which may be adaptive in predator-rich environments. Blocking tectal NPY2R increases baseline food intake and reduces or eliminates predator-induced changes in prey capture and food intake.

Tectal CRFR1 receptors modulate food intake and feeding behavior in the South African clawed frog Xenopus laevis.

The optic tectum and superior colliculus rapidly inhibit food intake when a visual threat is present. Previous work indicates that CRF, acting on CRFR1 receptors, may play a role in tectal inhibition of feeding behavior and food intake. Here we test the hypothesis that tectal CRFR1 receptors modulate food intake and feeding behavior in juvenile Xenopus laevis. We performed five experiments to test the following questions: 1) Does tectal CRF injection decrease food intake/feeding behavior? 2) Does a selective CRFR1 antagonist block CRF effects on feeding/feeding behavior? 3) Does a reactive stressor decrease food intake/feeding behavior? 4) Does a selective CRFR1 antagonist block reactive stress-induced decrease in feeding/feeding behavior? 5) Does food deprivation increase food intake/feeding behavior? Tectal CRF injections reduced food intake and influenced exploratory behavior, hindlimb kicks, and time in contact with food. These effects were blocked by the selective R1 antagonist NBI-27914. Exposure to a reactive stressor decreased food intake and this effect was blocked by NBI-27914. Neither food intake or feeding behavior changed following 1 wk of food deprivation. Overall, we conclude that activation of tectal CRFR1 inhibits food intake in juvenile X. laevis. Furthermore, tectal CRFR1 receptors appear to be involved in the reduction of food intake that occurs in response to a reactive stressor.

Tectal corticotropin-releasing factor (CRF) neurons respond to fasting and a reactive stressor in the African Clawed Frog, Xenopus laevis.

It is well established that hypothalamic neurons producing the peptide corticotropin-releasing factor (CRF) play a key role in stress adaptation, including reduction of food intake when a threat or stressor is present. We have previously reported on the presence of an intrinsic CRF signaling system within the optic tectum (OT), a brain area that plays a key role in visually guided prey capture/predator avoidance decisions. To better understand the potential role of tectal CRF neurons in regulating adaptive behavior and energy balance during stress we examined evidence for modulation of tectal CRF neuronal activity after stressor exposure and food deprivation in the African clawed frog Xenopus laevis. We tested two predictions, 1) that exposure to categorically distinct stressors (ether vapors and shaking) will reduce food intake and modulate the activity of tectal CRF cells, and 2) that food deprivation will modulate the activity of tectal CRF cells. Exposure to ether increased tectal content of CRF and CRF transcript, but lowed CRFR1 transcript abundance. Two weeks of food deprivation reduced total fat stores in frogs and decreased tectal content of CRF content while having no effect on CRF and CRFR1 transcript abundance. Our data are consistent with a role for tectal CRF neurons in modulating food intake in response to certain stressors.

Assessment of gonadal and thyroid histology in Gulf killifish (Fundulus grandis) from Barataria Bay Louisiana one year after the Deepwater Horizon oil spill.

We examined gonads and thyroid glands of Gulf killifish (Fundulus grandis) 1yr after the Deepwater Horizon oil spill. F. grandis were trapped from two impacted sites in Barataria Bay (Bayou St. Denis, Bay Jimmy) and an un-impacted site in East Texas (Sabine Pass). The greatest number of F. grandis were collected at Sabine Pass. F. grandis collected at Bayou St. Denis were smaller and had smaller Fulton condition factor scores than fish collected at Sabine Pass. Sex ratios were biased roughly 2:1 in favor of females at Sabine Pass and Bayou St. Denis. Gonad-somatic index (GSI) in males from Sabine Pass was double that of fish from Bay Jimmy while germinal epithelium thickness of the testes was 2.7 fold smaller in males from the impacted site. GSI and oocyte diameters in females from Bayou St. Denis were significantly smaller than females from Bay Jimmy or the reference site. There were no differences in thyroid follicle cell height. While total polyaromatic hydrocarbons at the impacted sites were no different from the reference site, the impacted sites did have greater concentrations of benzo[a]pyrene in sediment pore water. The finding of smaller GSI and testicular germinal epithelium in males from an impacted site suggest that exposure to a combination of oil and dispersants may adversely impact testicular function.

The role of the hypothalamus-pituitary-adrenal/interrenal axis in mediating predator-avoidance trade-offs.

Maintaining energy balance and reproducing are important for fitness, yet animals have evolved mechanisms by which the hypothalamus-pituitary-adrenal/interrenal (HPA/HPI) axis can shut these activities off. While HPA/HPI axis inhibition of feeding and reproduction may have evolved as a predator defense, to date there has been no review across taxa of the causal evidence for such a relationship. Here we review the literature on this topic by addressing evidence for three predictions: that exposure to predators decreases reproduction and feeding, that exposure to predators activates the HPA/HPI axis, and that predator-induced activation of the HPA/HPI axis inhibits foraging and reproduction. Weight of evidence indicates that exposure to predator cues inhibits several aspects of foraging and reproduction. While the evidence from fish and mammals supports the hypothesis that predator cues activate the HPA/HPI axis, the existing data in other vertebrate taxa are equivocal. A causal role for the HPA axis in predator-induced suppression of feeding and reproduction has not been demonstrated to date, although many studies report correlative relationships between HPA activity and reproduction and/or feeding. Manipulation of HPA/HPI axis signaling will be required in future studies to demonstrate direct mediation of predator-induced inhibition of feeding and reproduction. Understanding the circuitry linking sensory pathways to their control of the HPA/HPI axis also is needed. Finally, the role that fear and anxiety pathways play in the response of the HPA axis to predator cues is needed to better understand the role that predators have played in shaping anxiety related behaviors in all species, including humans.

Changes in gastric sodium-iodide symporter (NIS) activity are associated with differences in thyroid gland sensitivity to perchlorate during metamorphosis.

We investigated stage-dependent changes in sensitivity of the thyroid gland to perchlorate during development of African clawed frog tadpoles (Xenopus laevis) in relation to non-thyroidal iodide transporting tissues. Perchlorate-induced increases in thyroid follicle cell size and colloid depletion were blunted when exposures began at Nieuwkoop-Faber (NF) stage 55 compared to when exposures began at NF stages 49 or 1-10. To determine if the development of other iodide transporting tissues may contribute to this difference we first examined which tissues expressed transcripts for the sodium dependent iodide symporter (NIS). RT-PCR analysis revealed that NIS was expressed in stomach and small intestine in addition to the thyroid gland of X. laevis tadpoles. NIS mRNA was not detected in lung, kidney, skin, gill, muscle, heart or liver. Perchlorate sensitive (125)I uptake was found in stomach, lung, kidney, gill, and small intestine but not muscle, liver, or heart. Perchlorate-sensitive (125)I uptake by stomach was 6-10 times greater than in any other non-thyroidal tissue in tadpoles. While NF stage 49 tadpoles exhibited perchlorate-sensitive uptake in stomach it was roughly 4-fold less than that observed in NF stage 55 tadpoles. Although abundance of NIS gene transcripts was greater in stomachs from NF stage 55 compared to NF stage 49 tadpoles this difference was not statistically significant. We conclude that gastric iodide uptake increases between NF stages 49 and 55, possibly due to post-translational changes in NIS glycosylation or trafficking within gastric mucosal cells. These developmental changes in gastric NIS gene expression may affect iodide availability to the thyroid gland.

An intrinsic CRF signaling system within the optic tectum.

Previous work indicates that CRF administration inhibits visually guided feeding in amphibians. We used the African clawed frog Xenopus laevis to examine the hypothesis that CRF acts as a neurotransmitter in the optic tectum, the major brain area integrating the visual and premotor pathways regulating visually guided feeding in anurans. Reverse transcriptase PCR revealed that cells in the optic tectum express mRNA for CRF and the CRF R1 receptor but not the CRF R2 receptor. Radioligand binding studies indicated that specific binding of [(125)I]-Tyr-oCRF to tectal cell membranes can be displaced by the CRF R1 antagonists antalarmin or NBI-27914. CRF increased the expression of mRNA encoding regulator of G-protein signaling 2 (rgs2) in tectal explants and this effect was blocked by antalarmin. CRF had no effect on basal glutamate or gamma-aminobutyric acid (GABA) secretion but inhibited secretion of norepinephrine from tectal explants, an effect that completely blocked by antalarmin. Using a homologous radioimmunoassay we determined that CRF release from tectal explants in vitro was potassium- and calcium-dependent. Basal and depolarization-induced CRF secretion was greater from optic tectum than hypothalamus/thalamus, telencephalon, or brainstem. We concluded that the optic tectum possesses a CRF signaling system that may be involved in modulating communication between sensory and motor pathways involved in food intake.

Sub-chronic administration of fluoxetine does not alter prey-capture or predator avoidance behaviors in adult South African clawed frogs (Xenopus laevis).

Animals will halt foraging efforts and engage defensive behaviors in response to predator cues. Some researchers have proposed that the switch from appetitive to avoidance behavior resembles anxiety, but most work on this has been performed in a limited number of animal models, primarily zebrafish and rodents. We used adult South African clawed frogs (Xenopus laevis) to determine if the canonical anxiolytic fluoxetine alters predator-induced changes in appetitive and avoidance behavior in a laboratory-based trade-off task that mimics foraging/predator avoidance tradeoffs in the wild. We hypothesized that sub-chronic fluoxetine treatment (20 d) would not affect baseline behavior but would reverse predator-induced changes in food intake, appetitive and avoidance behavior, and the abundance of anxiety related gene transcripts in the optic tectum, a brain area central to ecological decision making in frogs. We found that fluoxetine significantly reduced baseline locomotion compared to vehicle-treated animals. Fluoxetine had no effect on appetitive and avoidance behaviors that were sensitive to predator cues in this assay and did not alter any of the anxiety-related transcripts in the tectum. We conclude that while peripheral sub-chronic administration of fluoxetine significantly reduces locomotion, it does not modify predator-induced changes in approach and avoidance behaviors in this assay. Our findings are not consistent with visual predator cues causing state anxiety in adult frogs.

Common health issues and advised treatments reported in an ultraendurance ocean rowing race.

OBJECTIVES: Ocean rowing is an extreme ultraendurance sport where individuals row unsupported across an ocean. This can mean months at sea in unpredictable and inhospitable conditions. The extreme physical and mental demands associated mean medical issues are common yet under researched, impacting the medical assistance provided. METHODS: The Talisker Whisky Atlantic Challenge provides a framework with safety protocols to create safer environments for athletes to attempt transatlantic crossings. Race logs, which record communication between rowers and safety teams, were anonymised and examined to create cumulative totals of medical issues requiring help and an incident timeline. RESULTS: Duty officers were notified of 65 medical complaints, 32% (n=21) requiring race doctors. Dermatological conditions were most common, accounting for 32% of complaints (n=21) and affecting 24% of rowers. Pressure sores and infections represented 43% and 38% of dermatological complaints respectively. Musculoskeletal injuries equalled 18% (n=12) of complaints, affecting 20% of rowers. Most cases were reported in weeks one and three, with 37% (n=24) of issues and 90% (n=10) of seasickness cases in week one. Hygiene and antibiotics were frequently advised management options. CONCLUSION: Conditions requiring race doctor input represent the most severe cases with the potential to deteriorate. Managing dermatological and musculoskeletal issues is vital throughout the race, while seasickness prophylaxis and education is essential in initial race stages. Infections are cause for concern, with gluteal pressure sores a potential route for secondary infections. Further research is required before evidence-based guidelines for management of health issues in ocean rowers can be introduced.

Stress Responses across the Scales of Life: Toward a Universal Theory of Biological Stress.

Although biological systems are more complex and can actively respond to their environment, an effective entry point to the development of a universal theory of biological stress is the physical concepts of stress and strain. If you apply stress to the end of a beam of steel, the strain will accumulate within that steel beam. If the stress is weak then the strain will disappear when the force is removed and the beam will return to its original state of form and functionality. If the stress is more severe, then the strain becomes permanent and the beam will be deformed, potentially losing some degree of functionality. In extremely stressful situations, the beam will break and lose most or all of its original functional capabilities. Although this stress-strain theory applies to the abiotic, stress and strain are also rules of life and directly relate to the form and function of living organisms. The main difference is that life can react and adjust to stress and strain to maintain homeostasis within a range of limits. Here, we summarize the rules of stress and strain in living systems ranging from microbes to multicellular organisms to ecosystems with the goal to identify common features that may underlie a universal biological theory of stress. We then propose to establish a range of experimental, observational, and analytical approaches to study stress across scales, including synthetic microbial communities that mimic many of the essential characteristics of living systems, thereby enabling a universal theory of biological stress to be experimentally validated without the constraints of timescales, ethics, or cost found when studying other species or scales of life. Although the range of terminology, theory, and methodology used to study stress and strain across the scales of life presents a formidable challenge to creating a universal theory of biological stress, working toward such a theory that informs our understanding of the simultaneous and interconnected unicellular, multicellular, organismal, and ecosystem stress responses is critical as it will improve our ability to predict how living systems respond to change, thus informing solutions to current and future environmental and human health challenges.

The hypothalamus-pituitary-thyroid axis in teleosts and amphibians: endocrine disruption and its consequences to natural populations.

Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health.

The organization of CRF neuronal pathways in toads: Evidence that retinal afferents do not contribute significantly to tectal CRF content.

Previous work has suggested that the peptide corticotropin-releasing factor (CRF) acts to inhibit visually guided feeding in anurans, but little is known about potential targets for CRF within the subcortical visuomotor circuitry. Here we investigated the relationship between CRF neuronal organization and visual pathways in toads. CRF-immunoreactive (ir) neurons and fibers were widely distributed throughout the ventral subpallial telencephalon and hypothalamus, although few fibers were found in telencephalic areas, such as the striatum, that are known to project to the tectum in anurans. Large populations of CRF-ir cells were observed in the bed nucleus of the stria terminalis and preoptic area as well as in the ventral infundibular hypothalamus. CRF-ir neurons and fibers also were observed in several midbrain and brain stem areas. Colchicine treatment significantly enhanced CRF-ir neurons and fibers throughout the brain, and revealed CRF-ir cell groups in several brain areas (including the dorsal hypothalamus) that were not observed in untreated animals. Intrinsic CRF-immunoreactive neurons were routinely observed in cell layer 8 and sometimes in layer 6 of the optic tectum in both untreated and colchicine-treated animals. CRF was detected in toad optic tectum by radioimmunoassay, although tectal CRF content was less than that of the hypothalamus and forebrain. Unilateral eye ablation did not affect CRF content of the contralateral optic tectum. We conclude that CRF-producing neurons are widely distributed in several areas of the toad brain known to be involved in regulating the behavioral, autonomic and endocrine response to stressors, including the optic tectum and several brain areas known to project to the optic tectum. Furthermore, retinal afferents do not contribute significantly to tectal CRF content.