Illness Behavior Research Articles

Self-stigma in suicide prevention of mental health professionals

Abstract Introduction Stigma is one of the main factors hindering help-seeking, which can have debilitating effects on mental health and even lead to suicidality. Stigma can affect the general public but also mental health professionals. In this study we examined mental-illness and help-seeking self-stigma as well as public stigma of suicidal behavior among suicidologists. Methods Invitation to participate in the study was sent to 518 member of the Internat.l Assoc. for Suicide Prevention. 89 participants (55 female, 34 male; 17% response rate) completed the survey. We gathered sociodemographic data, data on personal history of mental illness and suicidal behavior and on different types of stigma. We hypothesized that help-seeking self-stigma is predicted by sociodemographic attributes and personal history of mental illness and that self-stigma related to mental illness and suicide act as mediators. Results Personal experience with mental illness predicted mental illness self-stigma. There was no significant predictive value of other variables (age, gender, years working in suicidology) for self-stigma of mental illness and suicide behavior. Both types of self-stigma (mental illness and suicide behavior) were correlated. Mental-illness self-stigma was shown to be a stronger predictor of help-seeking self-stigma than self-stigma of suicide behavior, though the effect did not reach statistical significance. Self-stigma of suicide behavior showed no independent contribution to help-seeking self-stigma. Conclusions Mental healthcare professionals represent a particularly vulnerable group for developing mental health issues and suicidality. However, due to fear of being perceived less competent by colleagues and the public, they often disguise their mental struggles and are reluctant to seek help. These pilot findings warrant further research to better understand self-stigma and its impact on help-seeking behavior in order to prevent suicidality in this population.

Altered EEG, disrupted hippocampal long-term potentiation and neurobehavioral deficits implicate a delirium-like state in a mouse model of sepsis

Sepsis and systemic inflammation are often accompanied by severe encephalopathy, sleep disruption and delirium that strongly correlate with poor clinical outcomes including long-term cognitive deficits. The cardinal manifestations of delirium are fluctuating altered mental status and inattention, identified in critically ill patients by interactive bedside assessment. The lack of analogous assessments in mouse models or clear biomarkers is a challenge to preclinical studies of delirium. In this study, we utilized concurrent measures of telemetric EEG recordings and neurobehavioral tasks in mice to characterize inattention and persistent cognitive deficits following polymicrobial sepsis. During the 24-hour critical illness period for the mice, slow-wave EEG dominance, sleep disruption, and hypersensitivity to auditory stimuli in neurobehavioral tasks resembled clinical observations in delirious patients in which alterations in similar outcome measurements, although measured differently in mice and humans, are reported. Mice were tested for nest building ability 7 days after sepsis induction, when sickness behaviors and spontaneous activity had returned to baseline. Animals that showed persistent deficits determined by poor nest building at 7 days also exhibited molecular changes in hippocampal long-term potentiation compared to mice that returned to baseline cognitive performance. Together, these behavioral and electrophysiological biomarkers offer a robust mouse model with which to further probe molecular pathways underlying brain and behavioral changes during and after acute illness such as sepsis.

Indigenous Knowledge Pertaining to Health, Illness and Healthcare Seeking Behaviour Among Tribes of Chhattisgarh, India: A Comparative Explanation

Tribal population in India constitutes about 8.6 percent of the country’s total population and there are 705 recognized scheduled tribes in the country out of which 75 are declared Particularly Vulnerable Tribal Groups (PVTGs). Tribals reside in the hilly terrains, dense forests in the remote areas perched away from the mainstream depending upon the forests for their routine needs. The interaction of tribal people with nature is intertwined with their indigenous knowledge system, the knowledge which is held by the members of a particular community and evolved through many years of regular experimentation. It is handed down through generations by the mode of cultural transmission. The characteristic feature of indigenous knowledge is that it serves the day to day needs of the tribals and some crises situation of life including health. Health is an inevitable prerequisite is influenced by some common beliefs, practices and customs in any society. Like every culture, tribals as well have their own beliefs and practices with respect to the concept of health, disease and illness. The present study is conducted among tribes of Surguja district of Chhattisgarh and lays emphasis on highlighting the perceptions pertaining to health & illness and beliefs associated with their indigenous knowledge system.

Pubertal consumption of R. badensis subspecies acadiensis modulates LPS-induced immune responses and gut microbiome dysbiosis in a sex-specific manner

Puberty is a critical period of development characterized by significant brain remodeling and increased vulnerability to immune challenges. Exposure to an immune challenge such as LPS during puberty can result in inflammation and gut dysbiosis which may lead to altered brain functioning and psychiatric illnesses later in life. However, treatment with probiotics during puberty has been found to mitigate LPS-induced peripheral and central inflammation, prevent LPS-induced changes to the gut microbiota and protect against enduring behavioural disorders in a sex-specific manner. Recent findings from our laboratory revealed that pubertal R. badensis subspecies acadiensis (R. badensis subsp. acadiensis) treatment prevents LPS-induced depression-like behavior and alterations in 5HT1A receptor expression in a sex-specific manner. However, the underlying mechanism remains unclear. Thus, the aim of this study was to gain mechanistic insights and to investigate the ability of R. badensis subsp. acadiensis consumption during puberty to mitigate the effects of LPS treatment on the immune system and the gut microbiome. Our results revealed that pubertal treatment with R. badensis subsp. acadiensis reduced sickness behaviors in females more than males in a time-specific manner. It also mitigated LPS-induced increases in pro-inflammatory cytokines in the blood and in TNFα mRNA expression in the prefrontal cortex and the hippocampus of female mice. There were sex-dependent differences in microbiome composition that persisted after LPS injection or R. badensis subsp. acadiensis consumption. R. badensis subsp. acadiensis had greater impact on the microbiota of male mice but female microbiota’s were more responsive to LPS treatment. This suggested that female mice microbiota’s may be more prone to modulation by this probiotic. These findings emphasize the sex-specific effects of probiotic use during puberty on the structure of the gut microbiome and the immune system and highlight the critical role of gut colonization with probiotics during adolescence on immunomodulation and prevention of the enduring effects of infections.

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster.

Host behavioural changes are among the most apparent effects of infection. 'Sickness behaviour' can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here, using a real-time tracking and behavioural profiling platform, we show that in Drosophila melanogaster, several systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in some lethal infections. Using multiple bacteria and D. melanogaster immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with Micrococcus luteus, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the Toll ligand spätzle. In contrast, increased activity after infection with Francisella novicida, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of both Toll and the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.

Do adversities experienced over the early life course predict mental illness and substance use behaviour in adulthood: A birth cohort study

A range of adult health outcomes have been linked to early childhood adversities. These early adversities include parental marital breakdown and family economic disadvantage. Childhood experiences of maltreatment have also been linked to a variety of adult health outcomes. As both childhood adversities and child maltreatment often co-occur, we examine whether childhood adversities at 3 stages of the child's early life course predict any of nine adult mental health outcomes controlling for past experiences of child trauma (maltreatment).Data are from a long running birth cohort study, the Mater-University of Queensland Study of Pregnancy (MUSP). We use bivariate and multinomial logistic regression with adjustment for confounding, to predict adult outcomes.Experiences of recent life events in pregnancy appear to be unrelated to adult mental health. Recent life events experienced at the 5-year follow-up independently predicts lifetime ever depression and cannabis use disorder. Experiences of recent life events at 14-years of age predict lifetime ever depression, cannabis and amphetamine use in adulthood.Our findings support early childhood interventions which should be supplemented with a focus on later childhood and the adolescent period of development. Interventions should also focus on the broader social and demographic context within which children are born. Efforts to reduce the occurrence and consequences of childhood maltreatment should be given primary attention in order to reduce the childhood factors contributing to adult mental illness.

Early signals of parasitism expressed through behaviour but modulated by social context

Sickness behaviours are believed to be an adaptive response to infection. However, the degree to which these behaviours can be expressed may be impacted by an individual's social environment. Here we tested, first, whether parasitism reduces the activity behaviour of lambs, Ovis aries , second, whether this occurs prior to other observed costs of parasitism and, third, whether the infection status of other individuals affects the degree to which these behaviours are expressed. Sixty lambs were separated into replicate groups within three treatments: (1) parasitized: all lambs were infected with the parasitic nematode Teladorsagia circumcincta ; (2) nonparasitized; all lambs were dosed with water; (3) mixed: some of the group were infected and some were dosed with water. Activity behaviour was monitored before, during and after parasite infection. Parasitized groups had reduced activity levels following infection, and this occurred before any other impact or measure of parasitism was detected. Infected animals in the mixed groups had reduced activity levels following infection, but the level of change was less than that in animals in the fully parasitized groups. Activity levels remained low until lambs were treated with anthelmintic when activity levels of the groups that had been parasitized returned to the same level as nonparasitized groups. These findings show that parasite-induced behavioural changes occur earlier than other more commonly observed signals of infection, but the infection profile of an individual's group can shape these behavioural responses to infection. • Domestic lambs were experimentally infected with a gastrointestinal nematode. • Parasitized lambs had reduced activity levels following infection. • This occurred before any other measure or impact of parasitism was detected. • However, these behavioural changes were affected by group infection status. • Thus, an individual's social environment can affect their response to infection.

Attitudes and stigma toward seeking psychological help among Saudi Adults

BackgroundIn the Kingdom of Saudi Arabia (KSA), public attitudes and stigma toward mental health illness seem to prevent people from seeking psychological help, which negatively impacts an individual's life. The primary objective of this study was to investigate people's attitudes toward seeking psychological help and identify the extent to which the associated stigma is responsible for preventing them from seeking psychological help.MethodsTwo hundred eighteen adults recruited from the community living in the Eastern Province of the KSA completed the questionnaires, customized to create the Arabic version of Attitudes Toward Seeking Professional Psychological Help Scale-Short Form (ATSPPH-SF-A), the Arabic version of Stigma Scale for Receiving Psychological Help (SSRPH-A), and the Arabic version of Hopkins Symptom Checklist-25 (HSCL-25-A).ResultsBoth stigma and psychological distress significantly affected attitudes toward seeking professional help. Furthermore, it indicated that attitudes were negatively correlated with stigma while positively correlated with psychological distress. No significant difference in attitudes toward psychological help-seeking was identified between male and female participants. However, males displayed higher levels of stigma, while females showed greater psychological distress. Furthermore, the groups who received psychological treatment demonstrated more favorable attitudes toward seeking psychological help.ConclusionStigma and psychological stress influence attitudes toward treatment-seeking behavior for mental illness, making them two major predictors responsible for the underutilization of mental health services. More research is needed to assess specific sociodemographic disparities across more data sources and the factors that further contribute to stigma and psychological distress.

Brainstem ADCYAP1+ neurons control multiple aspects of sickness behaviour

Infections induce a set of pleiotropic responses in animals, including anorexia, adipsia, lethargy and changes in temperature, collectively termed sickness behaviours1. Although these responses have been shown to be adaptive, the underlying neural mechanisms have not been elucidated2–4. Here we use of a set of unbiased methodologies to show that a specific subpopulation of neurons in the brainstem can control the diverse responses to a bacterial endotoxin (lipopolysaccharide (LPS)) that potently induces sickness behaviour. Whole-brain activity mapping revealed that subsets of neurons in the nucleus of the solitary tract (NTS) and the area postrema (AP) acutely express FOS after LPS treatment, and we found that subsequent reactivation of these specific neurons in FOS2A-iCreERT2 (also known as TRAP2) mice replicates the behavioural and thermal component of sickness. In addition, inhibition of LPS-activated neurons diminished all of the behavioural responses to LPS. Single-nucleus RNA sequencing of the NTS–AP was used to identify LPS-activated neural populations, and we found that activation of ADCYAP1+ neurons in the NTS–AP fully recapitulates the responses elicited by LPS. Furthermore, inhibition of these neurons significantly diminished the anorexia, adipsia and locomotor cessation seen after LPS injection. Together these studies map the pleiotropic effects of LPS to a neural population that is both necessary and sufficient for canonical elements of the sickness response, thus establishing a critical link between the brain and the response to infection.

Comparison of Illness Behavior between Japanese and Chinese Patients with Somatoform Disorders

Aims: To clarify the differences between Japan and China regarding illness behavior of outpatients with somatoform disorders.
 Study Design: Cross-sectional study.
 Place and Duration of Study: A survey on psychiatric and psychological outpatients with somatoform disorders between Japan and China. Duration of this study was three months between April 1, 2011, and June 30, 2011.
 Methodology: The subjects of this research included 43 Japanese outpatients (49.7±10.5 yr., M/F:13/30) in psychiatry clinic at Saga Medical School Hospital, Saga 845-8502, Japan. It also included 38 Chinese outpatients (40.7±8.2 yr., M/F: 14/24) in psychiatry and psychology outpatient clinic in Dalian Medical University Hospital, Liaoning province, China. All psychiatric patients were diagnosed as the somatoform disorders according to the DSM-IV. To investigate the difference of psychological status and illness behavior, we examined them using two psychological instruments: Illness Behavior Questionnaire (IBQ) and General Health Questionnaire-30 (GHQ-30).
 Results: It can be found that there were the remarkable statistical differences between the Japanese and Chinese patients with somatoform disorders of each of the subscales of the GHQ-30. All GHQ-30 items were scored significantly higher by the Chinese than by the Japanese. Regarding the IBQ, the statistical differences of five subscales of IBQ between the two groups: General Hypochondriasis, Disease Conviction, Affective Inhibition, Affective Disturbance, and Irritability can be found. No obvious difference was found between the two groups of the subscale of Psychological versus somatic focusing (P/S) and Denial (D), however.
 Conclusion: The GHQ-30 and the other five subscales of IBQ (except for P/S and D) for Chinese was higher than for Japanese. This finding may be attribute to the socio-cultural and economic factors. P/S and D scores on the IBQ were not significantly different, suggesting the possibility of an essential symptom of somatoform disorders.

Portuguese Version of the Stigma Scale: Preliminary Psychometric Characteristics.

Stigma is associated with poor prognosis of illness and reduced help-seeking behavior, self-esteem and treatment compliance. The aims of this study were to study the reliability and construct validity of the King's et al Stigma Scale, and its association with Illness and Help-Seeking Behaviors scale (IHSBS) scores. One hundred and forty mental health patients filled out the Stigma scale and the Illness and Help-Seeking Behaviors scale. The exploratory factor analysis of the stigma scale was performed, and its reliability studied. The correlation analysis was used and mean differences in Stigma Scale scores among IHSBS groups were explored. The exploratory factor analysis indicated four factors (F): F1-Disclosure, F2-Discrimination, F3-Acceptance and F4-Personal Growth, which showed acceptable/good internal consistency (α from 0.70 to 0.91). Help-seeking behaviors were not associated with stigma. The levels of Discrimination were high in the group with global high-IHSB and in patients with medium/high illness behavior (IB) and health-related worries (HW). Additionally, Disclosure and overall stigma levels were higher in groups with high-HW and with medium-IB scores (when compared with the group with low-IB). The group with low-IB also had lower levels of Acceptance and Personal Growth when compared with the groups with medium-IB and high-IB, respectively. The Stigma Scale (27 items) is a valid, reliable instrument and useful tool to assess stigma in mental health patients.

Illness behaviour and influencing aspects of general practitioners in Germany and their use of the health care system: a qualitative study.

ObjectivesThe aim of this study was to explore aspects that play a role when general practitioners (GPs) become ill and thus gain a more comprehensive understanding of the overall illness behaviour of GPs and their use of the healthcare system.SettingPrimary care practices in Thuringia, Germany.ParticipantsConvenience sample of 16 GPs.DesignQualitative study design with semistructured interviews and content analysis.ResultsUsing our approach of having participants report their own episodes of illness, we found that self-treatment was practised and accepted by all 16 participants. The widespread use of naturopathy and complementary methods seems to be a special feature of German GPs. Formal use of the healthcare system mainly took place through direct consultation with specialists.Our study revealed various aspects influencing the illness behaviour of the GPs and their use of the healthcare system. Some aspects also apply to lay patients, but it became clear how strongly illness behaviour is influenced by participants’ activities as physicians. Noteworthy and less described aspects are especially the influence of patients and practice staff, the influence of biographical and professional imprint and the attitudes and values of the physicians.Complex inter-relationships were found between illness behaviour and influencing aspects; these are subjected to a dynamic and recursive process.ConclusionsThe illness behaviour of German GPs seems to be comprehensively influenced by their activities as responsible healthcare providers. The ability to perceive and reflect in this regards should already be actively promoted in studies and further education. Further research is needed for a better understanding of the inter-relationships.

Immunomodulatory effects of new phytotherapy on human macrophages and TLR4- and TLR7/8-mediated viral-like inflammation in mice.

BackgroundWhile all efforts have been undertaken to propagate the vaccination and develop remedies against SARS-CoV-2, no satisfactory management of this infection is available yet. Moreover, poor availability of any preventive and treatment measures of SARS-CoV-2 in economically disadvantageous communities aggravates the course of the pandemic. Here, we studied a new immunomodulatory phytotherapy (IP), an extract of blackberry, chamomile, garlic, cloves, and elderberry as a potential low-cost solution for these problems given the reported efficacy of herbal medicine during the previous SARS virus outbreak.MethodsThe key feature of SARS-CoV-2 infection, excessive inflammation, was studied in in vitro and in vivo assays under the application of the IP. First, changes in tumor-necrosis factor (TNF) and lnteurleukin-1 beta (IL-1β) concentrations were measured in a culture of human macrophages following the lipopolysaccharide (LPS) challenge and treatment with IP or prednisolone. Second, chronically IP-pre-treated CD-1 mice received an agonist of Toll-like receptors (TLR)-7/8 resiquimod and were examined for lung and spleen expression of pro-inflammatory cytokines and blood formula. Finally, chronically IP-pre-treated mice challenged with LPS injection were studied for “sickness” behavior. Additionally, the IP was analyzed using high-potency-liquid chromatography (HPLC)-high-resolution-mass-spectrometry (HRMS).ResultsLPS-induced in vitro release of TNF and IL-1β was reduced by both treatments. The IP-treated mice displayed blunted over-expression of SAA-2, ACE-2, CXCL1, and CXCL10 and decreased changes in blood formula in response to an injection with resiquimod. The IP-treated mice injected with LPS showed normalized locomotion, anxiety, and exploration behaviors but not abnormal forced swimming. Isoquercitrin, choline, leucine, chlorogenic acid, and other constituents were identified by HPLC-HRMS and likely underlie the IP immunomodulatory effects.ConclusionsHerbal IP-therapy decreases inflammation and, partly, “sickness behavior,” suggesting its potency to combat SARS-CoV-2 infection first of all via its preventive effects.

Need-emotional component in the pathogenesis of comorbid neurotic and addictive disorders

The article is devoted to the analysis of the features of the needemotional sphere of patients with neurotic disorders with addictions in their structure. The relevance (level of satisfaction) of the basic needs of the patients' personality and the structural features of their needemotional space are analyzed: the intensity of needs, their emotional content and correlation with specific situations, in particular with the situation of use and illness. It has been determined that neurotic illness and addictive behavior realize different needs: in anxiety-phobic disorders, the basis of the neurotic state is the tension of the needs for se- curity and rest, and addictive behavior is the need for communication and positive impressions; in dissociative disorders, a neurotic illness actualizes the need for communication and impressions, and the basis of addic- tive behavior is the need for rest and safety; in case of neurasthenia, neurotic illness and addictive behavior are options for getting out of the state of psychoemotional distress, but due to the realization of different needs: a neurotic state — needs for rest, addictive behavior — needs for communication.

Socs3 ablation in kisspeptin cells partially prevents lipopolysaccharide-induced body weight loss

Many cytokines have been proposed to regulate reproduction due to their actions on hypothalamic kisspeptin cells, the main modulators of gonadotropin-releasing hormone (GnRH) neurons. Hormones such as leptin, prolactin and growth hormone are good examples of cytokines that lead to Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation, consequently exerting effects in kisspeptin neurons. Different studies have investigated how specific components of the JAK/STAT signaling pathway affect the functions of kisspeptin cells, but the role of the suppressor of cytokine signaling 3 (SOCS3) in mediating cytokine actions in kisspeptin cells remains unknown. Cre-Loxp technology was used in the present study to ablate Socs3 expression in kisspeptin cells (Kiss1/Socs3-KO). Then, male and female control and Kiss1/Socs3-KO mice were evaluated for sexual maturation, energy homeostasis features, and fertility. It was found that hypothalamic Kiss1 mRNA expression is significantly downregulated in Kiss1/Socs3-KO mice. Despite reduced hypothalamic Kiss1 mRNA content, these mice did not present any sexual maturation or fertility impairments. Additionally, body weight gain, leptin sensitivity and glucose homeostasis were similar to control mice. Interestingly, Kiss1/Socs3-KO mice were partially protected against lipopolysaccharide (LPS)-induced body weight loss. Our results suggest that Socs3 ablation in kisspeptin cells partially prevents the sickness behavior induced by LPS, suggesting that kisspeptin cells can modulate energy metabolism in mice in certain situations.

Succinum extracts inhibit microglial-derived neuroinflammation and depressive-like behaviors.

Microglia are emerging as important targets for the treatment of neuropsychiatric disorders. The phagocytic microglial phenotype and the resulting neuroinflammation lead to synaptic loss and neuronal cell death. To explore potential candidates that inhibit microglial hyperactivation, we first investigated ten candidate extracts of traditional Chinese medicine (TCM) using lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Among the candidates, Pinus spp. succinum extract (PSE) was superior; thus, we further investigated its pharmacological activity and underlying mechanisms both in vitro and in vivo. Pretreatment with PSE (10, 20, and 40 μg/ml) attenuated the increases in inflammatory factors (nitric oxide and tumor necrosis factor-α), translocation of nuclear factor-kappa B (NF-κB), and phenotypic transformations (phagocytic and migratory) in a dose-dependent manner. These inhibitory effects of PSE on microglia were supported by its regulatory effects on the CX3C chemokine receptor 1 (CX3CR1)/nuclear factor erythroid-2-related factor 2 (Nrf2) pathway. In particular, intragastric administration of PSE (100 mg/kg) considerably improved sickness, anxiety, and depressive-like behaviors in mice subjected to chronic restraint stress (CRS). Our results suggest that PSE has strong antineuroinflammatory and antidepressant properties, and the underlying mechanisms may involve not only the regulation of NF-κB translocation but also the normalization of the CX3CR1/Nrf2 pathway.

Age-associated suppression of exploratory activity during sickness is linked to meningeal lymphatic dysfunction and microglia activation.

Peripheral inflammation triggers a transient, well-defined set of behavioral changes known as sickness behavior1-3, but the mechanisms by which inflammatory signals originating in the periphery alter activity in the brain remain obscure. Emerging evidence has established meningeal lymphatic vasculature as an important interface between the central nervous system (CNS) and the immune system, responsible for facilitating brain solute clearance and perfusion by cerebrospinal fluid (CSF)4,5. Here, we demonstrate that meningeal lymphatics both assist microglial activation and support the behavioral response to peripheral inflammation. Ablation of meningeal lymphatics results in a heightened behavioral response to IL-1β-induced inflammation and a dampened transcriptional and morphological microglial phenotype. Moreover, our findings support a role for microglia in tempering the severity of sickness behavior with specific relevance to aging-related meningeal lymphatic dysfunction. Transcriptional profiling of brain myeloid cells shed light on the impact of meningeal lymphatic dysfunction on microglial activation. Furthermore, we demonstrate that experimental enhancement of meningeal lymphatic function in aged mice is sufficient to reduce the severity of exploratory abnormalities but not pleasurable consummatory behavior. Finally, we identify dysregulated genes and biological pathways, common to both experimental meningeal lymphatic ablation and aging, in microglia responding to peripheral inflammation that may result from age-related meningeal lymphatic dysfunction.

Measuring respiratory syncytial virus infection severity in hospitalized children using the Pediatric Respiratory Syncytial Virus Electronic Severity and Outcome Rating System (PRESORS)

The Pediatric Respiratory Syncytial Virus Electronic Severity and Outcome Rating System (PRESORS) was developed to assess the severity of respiratory syncytial virus (RSV) infection in children. Because young children cannot report how they feel or function, ratings are based on observations by the child's caregiver (Observer-Reported Outcome questionnaire [ObsRO]) and clinician (Clinician-Reported Outcome questionnaire [ClinRO]). This prospective study aimed to evaluate the psychometric properties of the PRESORS. The PRESORS version 6 ObsRO and ClinRO were evaluated in children with RSV infection requiring hospitalization in centers in the United States, Argentina, and Chile. Assessments were performed from days 1 to 7 by the child's caregiver and clinician. To assess inter-rater reliability, two clinicians independently performed the ClinRO near in time. A total of 124 children aged ≤36 months were enrolled (mean age, 8months). Factor analysis demonstrated that RSV severity consists of two dimensions, respiratory signs and illness behavior, and that these dimensions were consistent over time. The inter-rater reliability for the ClinRO was 0.66 (95% confidence interval [CI], 0.55-0.75) but improved to 0.79 (95% CI, 0.71-0.86) after removing one outlying site, suggesting that quantifying RSV severity is not trivial, even using qualified raters, but that an adequate inter-rater reliability is achievable with the PRESORS through adequate training. ClinRO and ObsRO displayed acceptable internal consistency and acceptable convergent validity with the Respiratory Syncytial Virus Network Scale, global impression scores, and key hospital characteristics. The PRESORS is relevant and appropriate for assessing the severity of RSV infection in infants requiring hospitalization.

Acetyl-L-carnitine attenuates Poly I:C-induced sickness behavior in mice.

Fatigue is accompanied by a decrease in physical activity or malaise, and might be reduced by acetyl-L-carnitine (ALC) administration. The purpose of this study was to investigate the preventive effects of ALC on Poly I:C-induced sickness behavior in mice. For the experiment, male C3H/HeN mice were used and treated with ALC for 5 days before Poly I:C administration. ALC administration attenuated the decrease in wheel behavior activity of mice at 24h after Poly I:C administration and ALC-treated mice quickly recovered from the sickness behavior. The gene expression of brain-derived neurotrophic factor (BDNF) in the cerebrum and hippocampus, which is associated with physical activity, was higher in the ALC-treated group. Translocator protein 18kDa (TSPO), which has cytoprotective effects, was up-regulated in the cerebrum and hippocampus, suggesting that ALC suppressed the decrease in activity induced by Poly I:C treatment through enhancement of cytoprotective effects in the brain.

Curcumin Diethyl γ-Aminobutyrate, a Prodrug of Curcumin, for Enhanced Treatment of Inflammatory Pain.

Curcumin is a naturally occurring polyphenol compound with potential analgesic effects. It has been shown to improve pain-like behaviors in numerous models of pain. Despite its potential, curcumin exhibits poor physicochemical and pharmacokinetic properties, which hinder its oral therapeutic efficacy. Curcumin diethyl γ-aminobutyrate (CUR-2GE), a carbamate prodrug of curcumin, was designed to overcome these limitations and demonstrated greater anti-neuroinflammatory effects compared to curcumin in vitro. Thus, this study evaluated the effect of CUR-2GE and its parent compound on pain-like behaviors in carrageenan- and LPS-induced mouse models. The possible side effects of CUR-2GE were also assessed by exploring its effects on motor coordination and spontaneous locomotor activity after acute and chronic treatments. The results showed that CUR-2GE improved mechanical and thermal hyperalgesia and locomotor activity to a greater extent than curcumin in carrageenan-induced mice. These results are in line with the ability of CUR-2GE to suppress peripheral inflammation in the paw tissue of carrageenan-induced mice, indicated by a significant decrease in TNF-α and IL-6 expression levels. Similarly, in LPS-induced mice, CUR-2GE improved sickness and pain-like behaviors (exploratory behaviors and long-term locomotor activity) to a greater extent than curcumin. Furthermore, CUR-2GE significantly reduced the level of proinflammatory cytokines in both the plasma and spinal cord tissue of LPS-induced mice, exhibiting significantly higher inhibition than curcumin. Moreover, the motor coordination, and locomotive behaviors of mice were not affected by both acute and chronic administration of CUR-2GE, indicating no potential CNS side effects. Thus, CUR-2GE demonstrated enhanced therapeutic efficacy in mouse models of inflammatory pain without any possible CNS side effects, suggesting its potential to be developed as an analgesic agent against inflammatory pain.