Illness Behavior Research Articles

Central neural mechanisms of cancer cachexia.

Cachexia is a devasting syndrome which impacts a large number of patients with cancer. This review aims to provide a comprehensive overview of the central mechanisms of cancer cachexia. In particular, it focuses on the role of the central nervous system (CNS), the melanocortin system, circulating hormones and molecules which are produced by and act on the CNS and the psychological symptoms of cancer cachexia. A growing body of evidence suggests that a central mechanism of action underpins this multi-system disorder. Recent research has focused on the role of neuroinflammation that drives the sickness behaviour seen in cancer cachexia, with emphasis on the role of the hypothalamus. Melanocortin receptor antagonists are showing promise in preclinical studies. There are also new pharmacological developments to overcome the short half-life of ghrelin. GDF-15 has been identified as a core target and trials of compounds that interfere with its signalling or its central receptor are underway. Understanding the central mechanisms of cancer cachexia is pivotal for enhancing treatment outcomes in patients. While emerging pharmacological interventions targeting these pathways have shown promise, further research is essential.

Curcumin attenuates neuroinflammatory damage induced by LPS: implications for the role of S100B

Brain disease results in inflammatory damage that alters cell function in microglia and astrocytes as well as other neuronal cell types. Astrocytes modulate blood flow, regulate glutamate metabolism, and exert antioxidant protection. When responding to inflammatory damage, astrocytes enhance immune cell infiltration and amplify inflammatory responses via the upregulation of cytokine production. Several molecules have been proposed to attenuate neuroinflammation and control neurological diseases. Curcumin gained attention due to its capacity to cross the blood-brain barrier and its well-described anti-inflammatory and antioxidant activities. Our study aimed to understand if oral curcumin administration could protect against central nervous system inflammatory damage induced by intracerebroventricular injection of LPS while focusing on astrocyte function. Despite its poor bioavailability, we found that curcumin reaches the central nervous system, prevents the locomotory damage caused by LPS, and reduces inflammatory signaling via IL-1β and COX-2. Furthermore, we observed that curcumin was protective against LPS-induced S100B secretion in the cerebrospinal fluid and GSH reduction in the hippocampal tissue. However, curcumin could not protect the animals from anhedonia, assessed by the sucrose preference test, and weight loss induced by LPS. Our results indicate that oral curcumin administration exerts a protective anti-inflammatory action in the central nervous system, attenuating the sickness behavior induced by ICV LPS. This work demonstrates that curcumin has an important modulative effect on astrocytes, thus suggesting that astrocytes are critical to the anti-inflammatory effects of curcumin.

Gender-affirming care through the lens of abnormal illness behaviour and abnormal treatment behaviour.

To describe the increasing number and changing demographics of patients presenting with gender dysphoria and provide an account of patient- and clinician-related factors which may have contributed to these changes. The concept of abnormal illness behaviours introduced by Pilowsky, and its extension to the concept of abnormal treatment behaviours by Singh, provides a framework for understanding healthy and pathological interactions between gender dysphoria patients and their doctors. Abnormal illness behaviours driven by the reinforcing contingencies of gender-affirming care may explain, in part, the increasing number and changing demographics of gender dysphoria, as well as the increasing incidence of desistance and detransition. The under-diagnosis and under-treatment of mental health disorders by clinicians treating these patients are examples of abnormal treatment behaviours. Uncritical affirmation of patient reported gender identity appears likely to conceal unconscious motivations of some patients and clinicians, increasing the risks of harm to both.

Lipid Nanoparticles Elicit Reactogenicity and Sickness Behavior in Mice Via Toll-Like Receptor 4 and Myeloid Differentiation Protein 88 Axis.

mRNA therapeutics encapsulated in lipid nanoparticles (LNPs) offer promising avenues for treating various diseases. While mRNA vaccines anticipate immunogenicity, the associated reactogenicity of mRNA-loaded LNPs poses significant challenges, especially in protein replacement therapies requiring multiple administrations, leading to adverse effects and suboptimal therapeutic outcomes. Historically, research has primarily focused on the reactogenicity of mRNA cargo, leaving the role of LNPs understudied in this context. Adjuvanticity and pro-inflammatory characteristics of LNPs, originating at least in part from ionizable lipids, may induce inflammation, activate toll-like receptors (TLRs), and impact mRNA translation. Knowledge gaps remain in understanding LNP-induced TLR activation and its impact on induction of animal sickness behavior. We hypothesized that ionizable lipids in LNPs, structurally resembling lipid A from lipopolysaccharide, could activate TLR4 signaling via MyD88 and TRIF adaptors, thereby propagating LNP-associated reactogenicity. Our comprehensive investigation utilizing gene ablation studies and pharmacological receptor manipulation proves that TLR4 activation by LNPs triggers distinct physiologically meaningful responses in mice. We show that TLR4 and MyD88 are essential for reactogenic signal initiation, pro-inflammatory gene expression, and physiological outcomes like food intake and body weight─robust metrics of sickness behavior in mice. The application of the TLR4 inhibitor TAK-242 effectively reduces the reactogenicity associated with LNPs by mitigating TLR4-driven inflammatory responses. Our findings elucidate the critical role of the TLR4-MyD88 axis in LNP-induced reactogenicity, providing a mechanistic framework for developing safer mRNA therapeutics and offering a strategy to mitigate adverse effects through targeted inhibition of this pathway.

Maternal immune activation accelerates pup reflex development and alters immune proteins in pup stomach contents and brain

Prenatal infection increases the risk for neurodevelopmental disorders including autism spectrum disorder and schizophrenia. To better understand this link, a number of maternal immune activation (MIA) rodent models have been studied. However, the majority of these studies focus on adult behavioural outcomes that mirror adult symptoms related to neurodevelopmental disorders. There is little research reporting the effects of MIA on early postnatal development and even fewer using outbred mouse strains. Here, we use a modified version of the Fox scale to assess the effects of two MIA models, a bacterial model (LPS) and a viral model (PolyIC), on overall mouse pup sensorimotor development in CD-1 mice. Surprisingly, both bacterial and viral MIA models resulted in early reflex development when compared with control pups. To better characterize potential factors related to these changes, we examined indicators of sickness/inflammation in the immune-activated dams and in their pups. Sickness behaviour in the dams resulting from immune activation was assessed using a telemetry implant that allowed for continuous recording of temperature and activity in dams exposed to bacterial or viral immune activation. Although MIA dams showed reduced activity on the day immediately following MIA compared to controls, there was no evidence of fever. All dams showed elevated cytokines/chemokines associated with parturition, but this resolved by day 10 post-parturition and was unaffected by previous immune activation. Although circulating cytokines/chemokines in the dams were similar across MIA treatments, there were differences in the amount of interleukin-12p70 and interleukin-13 present in milk taken from milk bands in MIA pups, and interleukin-4 was overall decreased in LPS pup brain. These findings demonstrate that bacterial and viral models of MIA can result in similar precocious development in mice but differing long-term effects on inflammatory markers in both the milk provided to the pups and in their brains.

Insulin-Related Suicide Attempt in Non-Diabetic Pediatric Patient

Insulin analogs are basic drugs that are widely used in the treatment of diabetes around the world. Suicides with their use are described as rare, occurring mainly in the population of diabetic patients due to their easy access to the drug and knowledge of its properties. Among non-diabetic people, insulin is used for suicidal purposes mainly by adults with medical education. A case of a 15-year-old girl found unconscious by her mother at night was described. The patient was immediately transported to the hospital, where she was diagnosed with her first severe hypoglycemic episode of unknown origin. Once conscious and in a better state, the patient admitted to having taken insulin, which she had stolen from her diabetic mother, for suicidal purposes. The patient had no history of mental illness or self-destructive behavior. The patient was referred to psychiatric care. Suicides and suicide attempts involving insulin are usually observed among people with chronic diabetes. Moreover, such attempts are made by adults who know the mechanism of action of the drug. In the pediatric group without diabetes, such cases are extremely rare. Additionally, the issue of similar behaviors becomes very important due to the increasing popularity and availability of insulin therapy and the possibilities of obtaining information about using it to commit suicide from the Internet. Particular vigilance is required in pediatric emergency departments when a patient is identified as having a first episode of severe hypoglycemia of unknown origin.

Protocol for a randomized controlled trial of an internet-based prevention intervention for young children at-risk for functional abdominal pain

BackgroundChronic pain often clusters in families, where parents and their offspring both experience chronic pain conditions. Young children of parents with irritable bowel syndrome (IBS) represent an at-risk group for the development of abdominal pain, disability, and excess health care visits in later childhood. Parental solicitous responses to children’s expressions of discomfort and maternal modeling of their own illness behavior contribute to a greater focus on somatic sensations, leading to illness behaviors in children. This randomized controlled trial will test the effectiveness of an early preventive web-based psychosocial intervention (REACH)[TM] vs. an educational web-based safety comparison condition delivered to parents with IBS to alter parental responses and lead to improved child health and decreased health care costs.MethodsParents with IBS who have children ages 4–7 years are recruited via community-based approaches (e.g., social media advertisements, school electronic distribution, research networks) and health care providers. The target sample is 460 parents randomized to REACH, a web-based social learning and cognitive behavior therapy (SLCBT) intervention or an educational web-based safety comparison condition (EC). Participants will be assessed at baseline, 6-week (immediate post-intervention), 6-month, 12-month, and 18-month follow-up periods (months post-completion of intervention). The primary outcome is change in parental solicitous/protective behaviors. Secondary outcomes include parent risk and protective factors, child health and symptom outcomes, and health care utilization and cost savings.DiscussionThis study adapts a validated, parent-delivered intervention to treat chronic pain in children to a web-based application designed to prevent the development of chronic pain in very young, high-risk children. If successful, this strategy can both prevent adverse sequelae of this condition from developing as well as be widely accessible. Furthermore, the availability of a prevention model for parent training could result in significant short- and long-term health benefits across a broad spectrum of conditions.Trial registrationClinicalTrials.gov NCT05730491. Registered on February 15, 2023.

Sex-dependent effects of antimicrobials and lipopolysaccharide on blood-brain-barrier permeability in pubertal male and female CD1 mice

Exposure to stressors during puberty can disrupt normal development and possibly increase susceptibility to neurodegenerative disorders later in life. However, the mechanisms underlying the relationship between pubertal stress exposure and neurodegeneration remain unclear. As such, the current study was designed to examine the effects of pubertal antimicrobial (AMNS) and lipopolysaccharide (LPS) treatments on intestinal and blood-brain-barrier (BBB) permeability in male and female mice. Moreover, we also examined the sex-specific effects of pubertal AMNS and LPS treatments on gross motor activity, heart rate, and core body temperature. At four weeks of age, male and female CD1 mice were implanted with the G2 HR E-Mitter telemetry system. At five weeks of age, mice received 200 μL of broad-spectrum antimicrobial or water, through oral gavage, twice daily for seven days. Mice received an intraperitoneal injection of either saline or LPS at six weeks of age. BBB and intestinal permeability were examined 24 h, 72 h, and one week post-LPS/saline treatment. Telemetric data was collected for 48 h post-LPS/saline treatment. The results showed that pubertal AMNS and LPS treatments increased sickness behaviours and decreased body temperature and heart rate, in a sex-dependent manner. Furthermore, pubertal AMNS and LPS treatments resulted in sex-dependent regional increases in BBB permeability 24 h and 72 h post-LPS/saline treatment, while global increases in BBB permeability were only observed one week post-LPS/saline treatment. These results further our understanding of the combined effects of AMNS and LPS treatments on physiology and on the enduring negative changes observed following pubertal exposure to stressors.

Towards the outbreak tail, what is the public opinion about wastewater surveillance in the United States?

National opinions on a wide variety of public health topics can change over time and have highly contextual nuances. This study is a follow-up to prior inquiries into the knowledge of wastewater-based epidemiology, privacy concerns surrounding sample collection, and the use of data acquired, along with privacy awareness from an online survey conducted in the metropolitan United States during the winter of 2023. Mentions of wastewater-surveillance-related terms in the media remained common. Towards the outbreak tail in 2023, public support for surveillance of toxins (91%), diseases (91%), terrorist threats (87%), illicit drugs (70%), prescription medications (69%), and gun residue (60%) remained high. There was less support for surveillance of alcohol consumption (49%), mental illness (46%), healthy eating (37%), and lifestyle behaviors (35%). In terms of geographic scale, most respondents supported citywide surveillance (85%) with markedly lower levels of support for smaller (less anonymous) geographic scales covered by specific locations. Wastewater surveillance does not receive the public pushback that other COVID-19-related health system actors have witnessed. Instead, the public supports the expansion of wastewater surveillance as a standard to complement public health tools in other areas of health protection.

Quiescence Enhances Survival during Viral Infection in Caenorhabditis elegans.

Infection causes reduced activity, anorexia, and sleep, which are components of the phylogenetically conserved but poorly understood sickness behavior. We developed a Caenorhabditis elegans model to study quiescence during chronic infection, using infection with the Orsay virus. The Orsay virus infects intestinal cells yet strongly affects behavior, indicating gut-to-nervous system communication. Infection quiescence has the sleep properties of reduced responsiveness and rapid reversibility. Both the ALA and RIS neurons regulate virus-induced quiescence though ALA plays a more prominent role. Quiescence-defective animals have decreased survival when infected, indicating a benefit of quiescence during chronic infectious disease. The survival benefit of quiescence is not explained by a difference in viral load, indicating that it improves resilience rather than resistance to infection. Orsay infection is associated with a decrease in ATP levels, and this decrease is more severe in quiescence-defective animals. We propose that quiescence preserves energetic resources by reducing energy expenditures and/or by increasing extraction of energy from nutrients. This model presents an opportunity to explore the role of sleep and fatigue in chronic infectious illness.

Systematic review and tools appraisal of prognostic factors of return to work in workers on sick leave due to musculoskeletal and common mental disorders.

With the overall objective of providing implication for clinical and research practices regarding the identification and measurement of modifiable predicting factors for return to work (RTW) in people with musculoskeletal disorders (MSDs) and common mental disorders (CMDs), this study 1) systematically examined and synthetized the research evidence available in the literature on the topic, and 2) critically evaluated the tools used to measure each identified factor. A systematic search of prognostic studies was conducted, considering four groups of keywords: 1) population (i.e., MSDs or CMDs), 2) study design (prospective), 3) modifiable factors, 4) outcomes of interest (i.e., RTW). Studies showing high risk of bias were eliminated. Tools used to measure prognostic factors were assessed using psychometric and usability criteria. From the 78 studies that met inclusion criteria, 19 (for MSDs) and 5 (for CMDs) factors reaching moderate or strong evidence were extracted. These factors included work accommodations, RTW expectations, job demands (physical), job demands (psychological), job strain, work ability, RTW self-efficacy, expectations of recovery, locus of control, referred pain (back pain), activities as assessed with disability questionnaires, pain catastrophizing, coping strategies, fears, illness behaviours, mental vitality, a positive health change, sleep quality, and participation. Measurement tools ranged from single-item tools to multi-item standardized questionnaires or subscales. The former generally showed low psychometric properties but excellent usability, whereas the later showed good to excellent psychometric properties and variable usability. The rigorous approach to the selection of eligible studies allowed the identification of a relatively small set of prognostic factors, but with a higher level of certainty. For each factor, the present tool assessment allows an informed choice to balance psychometric and usability criteria.

Fevogrit, a polyherbal medicine, mitigates endotoxin (lipopolysaccharide)-induced fever in Wistar rats by regulating pro-inflammatory cytokine levels.

Fever is characterized by an upregulation of the thermoregulatory set-point after the body encounters any pathological challenge. It is accompanied by uncomfortable sickness behaviors and may be harmful in patients with other comorbidities. We have explored the impact of an Ayurvedic medicine, Fevogrit, in an endotoxin (lipopolysaccharide)-induced fever model in Wistar rats. Active phytoconstituents of Fevogrit were identified and quantified using ultra-high-performance liquid chromatography (UHPLC) platform. For the in-vivo study, fever was induced in male Wistar rats by the intraperitoneal administration of lipopolysaccharide (LPS), obtained from Escherichia coli. The animals were allocated to normal control, disease control, Paracetamol treated and Fevogrit treated groups. The rectal temperature of animals was recorded at different time points using a digital thermometer. At the 6-h time point, levels of TNF-α, IL-1β and IL-6 cytokines were analyzed in serum. Additionally, the mRNA expression of these cytokines was determined in hypothalamus, 24 h post-LPS administration. UHPLC analysis of Fevogrit revealed the presence of picroside I, picroside II, vanillic acid, cinnamic acid, magnoflorine and cordifolioside A, as bioactive constituents with known anti-inflammatory properties. Fevogrit treatment efficiently reduces the LPS-induced rise in the rectal temperature of animals. The levels and gene expression of TNF-α, IL-1β and IL-6 in serum and hypothalamus, respectively, was also significantly reduced by Fevogrit treatment. The findings of the study demonstrated that Fevogrit can suppress LPS-induced fever by inhibiting peripheral or central inflammatory signaling pathways and could well be a viable treatment for infection-induced increase in body temperatures.

The Impact of LPS on Inflammatory Responses in Alpha-Tocopherol Deficient Mice

BackgroundTo facilitate the evaluation of vitamin E (α-tocopherol, αT) status on health outcomes, the αT transfer protein knockout (Ttpa–/–) mouse model has proved to be an effective tool for lowering αT body stores. Our previous study showed a further reduction in grip strength in LPS-treated Ttpa–/– compared with wild-type (WT) mice during a 9-wk αT-deficient diet feeding period but did not find a difference in LPS-induced inflammatory response markers. Further optimization of this mouse model is warranted to determine the appropriate depletion period and biomarkers endpoints. ObjectivesThe objective was to examine whether 12 wk of an αT-deficient diet altered the inflammatory response 4 and/or 24 h after LPS injection in WT and Ttpa–/– mice. MethodsWT and Ttpa–/– weanling littermates were fed an αT-deficient diet ad libitum for 12 wk. Mice were then injected with LPS (10 μg/mouse) or saline (control) intraperitoneally and killed 4 (Study 1) or 24 h (Study 2) later. Concentrations of αT in tissues were measured via HPLC. Grip strength and burrowing were evaluated to assess sickness behaviors before/after LPS injection. Expression of genes related to inflammatory responses was examined via RT-PCR. ResultsαT concentrations in the brain, liver, and serum of Ttpa–/– mice were notably lower or undetectable compared with WT mice in both studies. Hepatic αT concentrations were further decreased 24 h after LPS injection. Grip strength was reduced at 4 h post-injection but partially recovered to baseline values 24 h after LPS injection. The expression of genes related to inflammatory responses were altered by LPS. However, neither measure of sickness behavior nor gene expression markers differed between genotypes. ConclusionsA 4-h LPS challenge reduced grip strength and resulted in an inflammatory response. At 24 h post-dosing, there was a partial, transitory recovery response in both Ttpa–/– and WT mice.

The proportion and determinants of appropriate health seeking behavior for febrile illness among caregivers of children under-five years in Butula sub-county, Busia county, Kenya

Background Almost 10 million children under the age of five in Kenya, die due to fever-related diseases. In Busia, a county in Kenya, malaria accounts for 13% of all child fatalities under the age of five, a number higher than any other county. This study aimed to determine (a) proportion of appropriate health-seeking behavior and (b) determinants of health-seeking behaviors (HSBs) among their caregivers in Butula Sub-County, Busia County, as reported by the caregivers. Methods This cross-sectional mixed-method study included 271 caregivers, 11 community health volunteers, and health facility workers in Butula Sub-County. Systematic random sampling for participants and purposive sampling for key informants were used. A questionnaire collected the data that was analysed using frequency and percentages and logistic regression. Results 70.1% of caregivers reported seeking care for a child's fever within 24 hours. Individual factors that caregivers reported to influence appropriate health-seeking HSB were unemployment (adjusted odds ratio (aOR) = 0.49, 95% CI: 0.217 – 0.593, p = 0.018), self-medication preference (aOR = 0.14, 95% CI: 0.054 – 0.363, p < 0.001), had atleast two children (aOR = 0.63, 95% CI: 0.425 – 0.937, p = 0.042), and confidence in identifying fever (aOR = 7.0, 95% CI: 2.200 – 22.439, p = 0.001). Health-system factors reported to influence HSBs were facility too far (aOR = 0.86, 95% CI: 0.526 – 0.914, p = 0.027), getting health education (aOR = 1.8, 95% CI: 1.201-4.122, p=0.015), and facility level (aOR = 4.4, 95% CI: 2.015 – 9.750, p < 0.001). Qualitative findings found health system factors related to HSB as stockouts, facility distance, and staff workload. Conclusions Policy and practice efforts should focus on significant individual and health system determinants for HSBs among caregivers of children under five with febrile illness.

Inflammation, oxidative stress and gut microbiome perturbation: A narrative review of mechanisms and treatment of the alcohol hangover.

Alcohol is the most widely abused substance in the world, the leading source of mortality in 15-49-year-olds, and a major risk factor for heart disease, liver disease, diabetes, and cancer. Despite this, alcohol is regularly misused in wider society. Consumers of excess alcohol often note a constellation of negative symptoms, known as the alcohol hangover. However, the alcohol hangover is not considered to have long-term clinical significance by clinicians or consumers. We undertook a critical review of the literature to demonstrate the pathophysiological mechanisms of the alcohol hangover. Hereafter, the alcohol hangover is re-defined as a manifestation of sickness behavior secondary to alcohol-induced inflammation, using the Bradford-Hill criteria to demonstrate causation above correlation. Alcohol causes inflammation through oxidative stress and endotoxemia. Alcohol metabolism is oxidative and increased intake causes relative tissue hypoxia and increased free radical generation. Tissue damage ensues through lipid peroxidation and the formation of DNA/protein adducts. Byproducts of alcohol metabolism such as acetaldehyde and congeners, sleep deprivation, and the activation of nonspecific inducible CYP2E1 in alcohol-exposed tissues exacerbate free radical generation. Tissue damage and cell death lead to inflammation, but in the intestine loss of epithelial cells leads to intestinal permeability, allowing the translocation of pathogenic bacteria to the systemic circulation (endotoxemia). This leads to a well-characterized cascade of systemic inflammation, additionally activating toll-like receptor 4 to induce sickness behavior. Considering the evidence, it is suggested that hangover frequency and severity may be predictors of the development of later alcohol-related diseases, meriting formal confirmation in prospective studies. In light of the mechanisms of alcohol-mediated inflammation, research into gut permeability and the gut microbiome may be an exciting future therapeutic avenue to prevent alcohol hangover and other alcohol-related diseases.

Contrasting Disease Progression, Microglia Reactivity, Tolerance, and Resistance to Toxoplasma gondii Infection in Two Mouse Strains.

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.

Animal Behaviour Packs a Punch: From Parasitism to Production, Pollution and Prevention in Grazing Livestock.

Behaviour is often the fundamental driver of disease transmission, where behaviours of individuals can be seen to scale up to epidemiological patterns seen at the population level. Here we focus on animal behaviour, and its role in parasite transmission to track its knock-on consequences for parasitism, production and pollution. Livestock face a nutrition versus parasitism trade-off in grazing environments where faeces creates both a nutritional benefit, fertilizing the surrounding sward, but also a parasite risk from infective nematode larvae contaminating the sward. The grazing decisions of ruminants depend on the perceived costs and benefits of the trade-off, which depend on the variations in both environmental (e.g., amounts of faeces) and animal factors (e.g., physiological state). Such grazing decisions determine the intake of both nutrients and parasites, affecting livestock growth rates and production efficiency. This impacts on the greenhouse gas costs of ruminant livestock production via two main mechanisms: (1) slower growth results in longer durations on-farm and (2) parasitised animals produce more methane per unit food intake. However, the sensitivity of behaviour to host parasite state offers opportunities for early detection of parasitism and control. Remote monitoring technology such as accelerometers can detect parasite-induced sickness behaviours soon after exposure, before impacts on growth, and thus may be used for targeting individuals for early treatment. We conclude that livestock host x parasite interactions are at the centre of the global challenges of food security and climate change, and that understanding livestock behaviour can contribute to solving both.

Community perspectives to inform the development of a radio program to destigmatize mental illness in rural Uganda: a qualitative study

Background The stigma attached to mental illness impedes diagnosis, treatment, and access to care for people with mental illness. Scalable interventions are needed to enhance attitudes towards seeking treatment, foster community support, and promote acceptance of individuals experiencing mental illness. We worked with community health workers in the Busoga region of eastern Uganda to develop a radio program aimed at reducing mental illness stigma. We piloted the radio program in focus groups, purposively sampling people with families affected by mental illness and people with families unaffected by mental illness, to understand their perspectives about the program’s acceptability and potential effectiveness. Methods The 45-minute radio program was adapted from a previously studied community-led theater intervention, produced by community health workers, that demonstrated an individual’s recovery from mental illness. Afterward, we conducted 2 focus group discussions, each involving six participants: n=12; and 17 one-on-one, in-depth interviews. We employed the framework method to inductively identify themes and sub-themes. Results Participants reported greater understanding of causes of mental illness, treatment options, and greater acceptance of those with mental illness as a result of listening to the program. Conclusions This radio program intervention showed potential to change healthcare seeking behavior for mental illness and to decrease mental illness stigma in rural Uganda. Further investigation is needed to assess the broader applicability of this approach.

Associations between sickness behavior, but not inflammatory cytokines, and psychiatric comorbidity in chronic pain

ObjectivesApproximately 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. MethodsSelf-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. ResultsParticipants 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. ConclusionsParticipants 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.

A plant-derived δ opioid receptor agonist rubiscolin-6 ameliorates sickness behavior in mice with cancer cachexia

Cancer cachexia, which encompasses a range of sickness behaviors such as anorexia, reduced locomotor activity, and depression, diminishes quality of life and increases mortality in cancer patients. Rubiscolin-6 is a hexapeptide derived from ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), a major plant leaf protein. Previous reports have demonstrated that rubiscolin-6 functions as an agonist of the δ opioid receptor, inducing diverse effects such as orexigenic, antinociceptive, and antidepressant-like effects. In this study, we investigated the effects of rubiscolin-6 on sickness behavior in colon26-bearing cachexia model mice. Intraperitoneal administration of rubiscolin-6 enhanced food intake in cachexic mice with chronic anorexia. It also increased locomotor activity, which decreased in cachexic mice, as assessed by the open field test. Moreover, the tail suspension test revealed that rubiscolin-6 alleviated depression-like behavior in mice with cachexia. These findings imply that rubiscolin-6 could be used to ameliorate the sickness behavior associated with cancer cachexia.