Pathogens not only cause mortality but also impose nonlethal fitness consequences. Snakes experience trade-offs associated with behaviors that combat disease but divert time and energy away from other critical activities. The impacts of such behaviors on fitness remain poorly understood, raising concerns amid the emergence of novel herpetofaunal diseases. Ophidiomycosis, caused by the ascomycete fungus Ophidiomyces ophidiicola, impacts free-ranging snakes across North America and has been implicated in declines of several imperiled populations. Although previous ophidiomycosis research has primarily focused on disease-related mortality, few studies have evaluated nonlethal impacts on snake fitness. To address this knowledge gap, we investigated the effects of apparent ophidiomycosis on the behavior, habitat use, and movement of snakes in central New Jersey, USA, from 2020 to 2021. Our focal species was the eastern copperhead (Agkistrodon contortrix), a state species of special concern with limited representation in the ophidiomycosis literature. Although we did not observe mortality in our study population, we found that copperheads with apparent ophidiomycosis (8/31 individuals) displayed significantly different thermoregulatory behaviors than snakes without ophidiomycosis. Specifically, individuals with apparent ophidiomycosis favored areas with less canopy cover, less rock cover, and more coarse woody debris. Our findings suggest that snakes with apparent ophidiomycosis select habitats conducive to initiating behavior-mediated fever, potentially facilitating recovery.

Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with the previously documented outcomes in BALB/c mice using an identical ocular route and parasite burden (2 × 105 tachyzoites), with saline as the control. Contrary to expectations, the Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while the survivors exhibited no apparent signs of infection. Comparative analysis revealed the T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while the infected Swiss albino mice showed enhanced avoidance responses. There was an important increase in microglial cells in the dentate gyrus molecular layer of the infected Swiss albino mice compared to the BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses identified three microglial morphological clusters, differentially affected by T. gondii infection across strains. The BALB/c mice exhibited increased microglial branching and complexity, while the Swiss albino mice showed reduced shrunken microglial arbors, diminishing their morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory regulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and resistance. Understanding these elements is critical in devising control measures for toxoplasmosis.

BACKGROUND: One of the most common entry gates for systemic infection is the lung. In humans, pulmonary infections can lead to significant neurological impairment, ranging from acute sickness behavior to long-term disorders. Surfactant proteins (SP), essential parts of the pulmonary innate immune defense, have been detected in the brain of rats and humans. Recent evidence suggests that SP-A, the major protein component of surfactant, also plays a functional role in modulating neuroinflammation. This study aimed to determine whether SP-A deficiency affects the inflammatory response in the brain of adult mice during pulmonary infection.
METHODS: Adult male wild-type (WT, n = 72) and SP-A-deficient (SP-A-/-, n = 72) mice were oropharyngeally challenged with lipopolysaccharide (LPS), Pseudomonas aeruginosa (P. aeruginosa), or PBS (control). Both, behavioral assessment and subsequent brain tissue analysis, were performed 24, 48, and 72 h after challenge. The brain concentrations of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β were determined by ELISA. Quantitative rtPCR was used to detect SP-A mRNA expression in brain homogenates and immunohistochemistry was applied for the detection of SP-A protein expression in brain coronal slices.
RESULTS: SP-A mRNA and histological evidence of protein expression were detected in both the lungs and brains of WT mice, with significantly higher amounts in lung samples. SP-A-/- mice exhibited significantly higher baseline concentrations of brain TNF-α, IL-6, and IL-1β compared to WT mice. Oropharyngeal application of either LPS or P. aeruginosa elicited significantly higher brain levels of TNF-α and IL-1β in SP-A-/- mice compared to WT mice at all time points. In comparison, behavioral impairment as a measure of sickness behavior, was significantly stronger in WT than in SP-A-/- mice, particularly after LPS application.
CONCLUSIONS: SP-A is known for its anti-inflammatory role in the pulmonary immune response to bacterial infection. Recent evidence suggests that in an abdominal sepsis model SP-A deficiency can lead to increased cytokine levels in the brain. Our results extend this perception and provide evidence for an anti-inflammatory role of SP-A in the brain of adult WT mice after pulmonary infection.

OBJECTIVE: Approximately one in five adults experiences chronic pain, often in co-occurrence with depression, insomnia, anxiety, and lower self-rated health. Elevated levels of cytokines, e.g. tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10), have been identified in patients with chronic pain. Depression, insufficient sleep, poor self-rated health, and pain intensity have also been associated with inflammatory biomarkers. This study aimed to investigate the interrelationships between inflammatory biomarkers and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity in patients with chronic pain.
METHODS: Self-report questionnaires and blood samples analyzed for plasma levels of inflammatory biomarkers were collected from 80 adult patients with chronic pain. Associations between inflammatory biomarkers (TNF-α, IL-6, IL-8, IL-10, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)) and depression, insomnia, anxiety, self-rated health, sickness behavior, and pain intensity, were analyzed using bivariate Spearman rank correlation coefficients and regression analyses.
RESULTS: Participants were mainly women (72.5 %), with a mean age of 50.8 years, and a reported mean pain duration of 16.7 years. There were significant correlations between insomnia and CRP (rs =.26, p <.05); sex and ESR (rs =.29, p <.05); age and IL-6 (rs =.29, p <.05) and IL-8 (rs =.30, p <.05); BMI and IL-6 (rs =.50, p <.001), CRP (rs =.63, p <.001) and ESR (rs =.42, p <.001). Ratings of depression were positively and significantly related to ratings of sickness behavior and anxiety (β =.32 and β =.40, respectively), explaining 49 % of the total variance in depression ratings. Insomnia was positively and significantly related to sickness behavior (β =.37) explaining 31 % of the total variance in insomnia ratings. Inflammatory biomarkers, however, did not contribute significantly to the models.
CONCLUSIONS: Participants reported high levels of symptoms, yet the associations between these ratings and the inflammatory biomarkers were either absent or weak. Also, despite high levels of self-reported sickness behavior, overall the inflammatory status remained within the normal range. Ratings of sickness behavior contributed more than inflammatory markers in explaining ratings of depression and insomnia. The present results point to the complexity of chronic pain, and the challenges of identifying biomarkers that explain symptomatology.

Much has been learned about the neurotoxicity of aluminum over the past several decades in terms of its ability to disrupt cellular function, result in slow accumulation, and the difficulty of its removal from cells. Newer evidence suggests a central pathophysiological mechanism may be responsible for much of the toxicity of aluminum and aluminofluoride compounds on the brain and spinal cord. This mechanism involves activation of the brain\'s innate immune system, primarily the microglia, astrocytes, and macrophages, with a release of neurotoxic concentrations of excitotoxins and proinflammatory cytokines, chemokines, and immune mediators. Many studies suggest that excitotoxicity plays a significant role in the neurotoxic action of several metals, including aluminum. Recently, researchers have found that while most of the chronic pathology involved in the observed neurodegenerative effects of these metals are secondary to prolonged inflammation, it is the enhancement of excitotoxicity by the immune mediators that are responsible for most of the metal\'s toxicity. This enhancement occurs through a crosstalk between cytokines and glutamate-related mechanisms. The author coined the name immunoexcitotoxicity to describe this process. This paper reviews the evidence linking immunoexcitotoxicity to aluminum\'s neurotoxic effects and that a slow accumulation of aluminum may be the cause of neurodevelopmental defects as well as neurodegeneration in the adult.

By definition, ill and injured animals are on the negative valence of animal welfare. For beef cattle kept in feedlot settings, advances in cattle health management have resulted in a greater understanding and prevention of illness and injury. However, the management of cattle once they become ill and injured is an understudied area, and there are gaps in knowledge that could inform evidence-based decision-making and strengthen welfare for this population. The aim of this review is to provide a comprehensive overview of the acquired knowledge regarding ill and injured feedlot cattle welfare, focusing on existing knowledge gaps and implications for hospital and chronic pen management and welfare assurance. Ill and injured feedlot cattle consist of acutely impaired animals with short-term health conditions that resolve with treatment and chronically impaired animals with long-term health conditions that may be difficult to treat. A literature search identified 110 articles that mentioned welfare and ill and injured feedlot cattle, but the population of interest in most of these articles was healthy cattle, not ill and injured cattle. Articles about managing ill and injured cattle in specialized hospital (n = 12) or chronic (n = 2) pens were even more sparse. Results from this literature search will be used to outline the understanding of acutely and chronically ill and injured feedlot cattle, including common dispositions and welfare considerations, behavior during convalescence, and strategies for identifying and managing ill and injured cattle. Finally, by working through specific ailments common in commercial feedlot environments, we illustrate how the Five Domains Model can be used to explore feelings and experiences and subsequent welfare state of individual ill or injured feedlot cattle. Using this approach and our knowledge of current industry practices, we identify relevant animal-based outcomes and critical research questions to strengthen knowledge in this area. A better understanding of this overlooked topic will inform future research and the development of evidence-based guidelines to help producers care for this vulnerable population.

Social withdrawal is a well-established part of sickness behavior, but in some contexts sick animals might gain from keeping close instead of keeping away. For instance, sick individuals are more willing to be near known individuals who can provide care and safety (close others) compared to when healthy. Yet, interactions with some strangers might also be beneficial (i.e., healthcare professionals), but it is not known how sickness interplay with social behavior towards such individuals. Here, we assessed if sickness affects perception of caregivers, and developed a new task, the Caregiver Perception Task (CgPT). Twenty-six participants performed the CgPT, once after an injection of lipopolysaccharide (LPS, 0.8 ng/kg body weight, n = 24), and once after an injection of saline (n = 25), one hour and forty-five minutes post-injection. During the task, participants watched short video clips of three types of caregivers: a healthcare professional taking care of a sick individual, a healthcare professional not taking care of a sick individual, and a non-healthcare professional taking care of their sick adult child or partner. After each video clip, the likability, trustworthiness, professionalism, and willingness to interact with and receive care from the caregiver were rated on visual analogue scales. Results showed that participants injected with saline rated healthcare professionals who did not take care of a sick individual less positively on all aspects compared to healthcare professionals who took care of a sick individual. Moreover, compared to saline, LPS increased the participants\' willingness to receive care from healthcare professionals and non-healthcare professionals providing care, but not from healthcare professionals not providing care. Thus, our results indicate that sick individuals may approach unknown individuals with potential to provide care and support.

UNASSIGNED: An increasing number of studies have indicated the important role of cytokines in the development of depressive disturbances (DD). In medically ill patients, cytokines can provoked sickness behavior, the signs of which resemble DD. This results in alterations in behavior to limit energy expenditure and redirect it to cope with particular diseases. The aim of our study was to investigate the role of pro-inflammatory IL-6, TNF-α, and IL-1β and anti-inflammatory IL-10 and TGF-β in DD observed in patients suffering from pain caused by disk herniation (DH) qualified for surgery.
UNASSIGNED: The intensity of DD assessed by using Beck Depression Inventory, pain intensity, and functional impairment were evaluated in 70 patients with DH who were qualified for surgery. Pro-inflammatory serum levels of TNF-α, IL-1, IL-6, anti-inflammatory TGF-β, and IL-10 were measured.
UNASSIGNED: Elevated serum levels of TGF-β, IL-10, and IL-6 were found in the group with moderate and severe depressive symptoms (SD) compared with the groups with mild (MD) or no depressive symptoms (ND). TGF-β levels were negatively correlated with pain intensity, as assessed using the Present Pain Intensity scale in SD. Functional impairment measured using the Oswestry Disability Index was the most advanced in SD group.
UNASSIGNED: Results of our study can suggest association between depressive disturbances and anti-inflammatory cytokines TGF-β and IL-10. Functional impairment of SD group is more severe but serum levels of TGF-β and IL-10, which are involved in the healing processes, are increased.

Pathogenic infection elicits behaviors that promote recovery and survival of the host. After exposure to the pathogenic bacterium Pseudomonas aeruginosa PA14, the nematode Caenorhabditis elegans modifies its sensory preferences to avoid the pathogen. Here, we identify antagonistic neuromodulators that shape this acquired avoidance behavior. Using an unbiased cell-directed neuropeptide screen, we show that AVK neurons upregulate and release RF/RYamide FLP-1 neuropeptides during infection to drive pathogen avoidance. Manipulations that increase or decrease AVK activity accelerate or delay pathogen avoidance, respectively, implicating AVK in the dynamics of avoidance behavior. FLP-1 neuropeptides drive pathogen avoidance through the G protein-coupled receptor DMSR-7, as well as other receptors. DMSR-7 in turn acts in multiple neurons, including tyraminergic/octopaminergic neurons that receive convergent avoidance signals from the cytokine DAF-7/transforming growth factor β. Neuromodulators shape pathogen avoidance through multiple mechanisms and targets, in agreement with the distributed neuromodulatory connectome of C. elegans.

Administration of low-dose lipopolysaccharide (LPS) to healthy humans is a translational approach to analyze the effects of acute systemic inflammation and sickness behavior. Although studies documented that LPS-induced inflammation can alter social behavior, its impact on empathy remains poorly understood. In this double-blind, placebo-controlled study, 52 healthy female volunteers received an intravenous injection of either LPS (0.4 ng/kg body weight) or placebo and completed the Social Interaction Empathy Task (SIET) two hours after injection. Physiological responses (blood pressure, heart rate, body temperature, cytokines, cortisol) were analyzed along with sickness symptoms and mood before and after LPS or placebo administration. LPS application led to significant increases in plasma cytokines and sickness symptoms as well as low mood. Moreover, volunteers receiving LPS showed significantly less empathy for other\'s psychological pain than those who received placebo. Furthermore, LPS-injected volunteers with more severe sickness symptoms displayed higher pain ratings in the first-person perspective. Thus, low-grade inflammation reduces empathy for other\'s psychological pain which might reflect an adaptive strategy to save energy by not responding empathetically when sick oneself.