[Systemic inflammation, "sickness behavior" and expectations : What role do expectations play in inflammation-associated symptoms?] / Systemische Entzündung, "Sickness Behavior" und Erwartungsprozesse : Welche Rolle spielen Erwartungen bei entzündungsassoziierten Symptomen?

BACKGROUND: Systemic inflammation is accompanied by unspecific physical and psychological symptoms of sickness, including pain and affective symptoms. These symptoms (commonly called "sickness behavior") are mediated by the central nervous effects of immune messengers such as pro-inflammatory cytokines. While adaptive during acute inflammation, sickness symptoms can have detrimental effects on quality of life during chronic inflammation and may contribute to comorbidity in chronic pain conditions. Despite the high clinical relevance of sickness behavior, psychological interventions aiming to modulate sickness symptoms have hardly been investigated. One approach could be the use of expectation effects, since positive and negative expectations (placebo or nocebo effects) have been shown to have an influence on pain and affect-related symptoms. OBJECTIVES: Herein, we summarize immunological and psychobiological factors that contribute to pain in the context of sickness behavior, with a major focus on findings from experimental endotoxemia. Against this background, we discuss how expectations could help to improve immune-mediated sickness symptoms and outline potential psychological and psychobiological mechanisms underlying this putative effect.

The development and psychometric evaluation of FABIANA-checklist: a scale to assess factors influencing treatment initiation in anorexia nervosa.

BACKGROUND: A long duration of untreated illness (DUI) is an unfavorable prognostic factor in anorexia nervosa (AN) and is associated with chronic illness progression. Although previous preventive measures aimed at reducing DUI and thus improving short- and long-term treatment outcomes have been partially successful, a better understanding of the factors involved in the sensitive phase prior to treatment initiation is needed. To date, there is no validated instrument available to assess these factors specifically for patients with AN. The FABIANA-project (Facilitators and barriers in anorexia nervosa treatment initiation) aims at identifying predictors of the DUI in order to target preventive measures better in the future. As part of this project, the FABIANA-checklist was developed, based on a multi-informant perspective and a multimodal bottom-up approach. The present study focusses on the process of item generation, item selection and psychometric validation of the checklist. METHODS: Based upon a previous qualitative study, an initial set of 73 items was generated for the most frequently mentioned facilitators and barriers of treatment initiation in AN. After a process of consensual rating and cognitive pre-testing, the resulting 25-item version of the FABIANA-checklist was provided to a sample of female patients (N = 75), aged ≥ 14 years with AN that underwent their first psychotherapeutic treatment in the last 12 months. After item analysis, dimensionality of the final version of the FABIANA-checklist was tested by Principal Component Analysis (PCA). We evaluated construct validity assuming correlations with related constructs, such as perceived social support (F-SozU), support in the health care system (PACIC-5A), illness perception and coping (BIPQ). RESULTS: We included 54 adult and 21 adolescent patients with AN, aged on average 21.4 years. Average BMI was 15.5 kg/m2, age of onset was 19.2 years and average DUI was 2.25 years. After item analysis, 7 items were excluded. The PCA of the 18-item-FABIANA-checklist yielded six components explaining 62.64% of the total variance. Overall internal consistency was acceptable (Cronbach's α = .76) and construct validity was satisfactory for 14 out of 18 items. Two consistent components emerged: "primary care perceived as supportive and competent" (23.33%) and "emotional and practical support from relatives" (9.98%). With regard to the other components, the heterogeneity of the items led to unsatisfactory internal consistency, single item loading and in part ambiguous interpretability. CONCLUSIONS: The FABIANA-checklist is a valid instrument to assess factors involved in the process of treatment initiation of patients with AN. Psychometrics and dimensionality testing suggests that experienced emotional and practical support from the primary health care system and close relatives are main components. The results indicate that a differentiated assessment at item level is appropriate. In order to quantify the relative importance of the factors and to derive recommendations on early-intervention approaches, the predictive effect of the FABIANA-items on the DUI will be determined in a subsequent study which will further include the perspective of relatives and primary caregivers. Trial registration Clinical Trials.gov Identifier: NCT03713541: https://clinicaltrials.gov/ct2/show/NCT03713541 .

Early treatment contributes to a more favorable illness course and an improved prognosis in patients with anorexia nervosa (AN). The current study presents the development of the FABIANA checklist, which aims to assess factors which influence duration of untreated illness. The FABIANA checklist was developed on the basis of interviews with patients, their relatives and primary care practitioners. It provides data from the first use of the checklist in a German sample of 75 patients with AN. The results of our study suggest that the FABIANA-checklist is a valid instrument to assess factors involved in the process of treatment initiation. Emotional and practical support from the primary health care system and close relatives were the most consistent components. A follow-up study will investigate the relationship between the FABIANA-items and the DUI in order to guide the conception of effective secondary prevention measures.

Acute Versus Chronic Administration of Calcineurin-Inhibitors Differentially Affect T-Cell Function.

BACKGROUND: Calcineurin-inhibitors (CNI) are used in renal transplant patients (RTX) to prevent rejection. CNI mainly suppress T-cell mediated immunity but very little is known about the impact of long-term treatment with CNI on T-cell function. OBJECTIVE: We investigated the immunological effects of long-term CNI intake in RTX patients in comparison to short-term CNI administration in healthy controls (HC). METHODS: Blood was drawn from 30 RTX patients with long-term CNI treatment. In addition, blood was sampled from HC with short-term CNI treatment (four dosages) before the first and 2 hours after the last CsA intake. T-cells were analyzed for cytokine production, proliferation, and CD25 expression. RESULTS: Short-term CNI reduced T-cell derived IL-2 and IFNγ as well as T-cell proliferation in HC. IFNγ was not suppressed in patients with long-term CNI treatment. IL-2 production, CD25 expression, and T-cell proliferation were enhanced in long-term CNI patients. CONCLUSION: Suppression of IFNγ/IL-2 and T-cell proliferation is weaker during long-term CNI treatment in patients compared to short-term treatment in healthy subjects. Enhanced CD25 expression may lower the threshold for T-cell activation during long-term CNI treatment.

Learned immunosuppressive placebo responses in renal transplant patients.

Patients after organ transplantation or with chronic, inflammatory autoimmune diseases require lifelong treatment with immunosuppressive drugs, which have toxic adverse effects. Recent insight into the neurobiology of placebo responses shows that associative conditioning procedures can be employed as placebo-induced dose reduction strategies in an immunopharmacological regimen. However, it is unclear whether learned immune responses can be produced in patient populations already receiving an immunosuppressive regimen. Thus, 30 renal transplant patients underwent a taste-immune conditioning paradigm, in which immunosuppressive drugs (unconditioned stimulus) were paired with a gustatory stimulus [conditioned stimulus (CS)] during the learning phase. During evocation phase, after patients were reexposed to the CS, T cell proliferative capacity was significantly reduced in comparison with the baseline kinetics of T cell functions under routine drug intake (ƞp2 = 0.34). These data demonstrate, proof-of-concept, that learned immunosuppressive placebo responses can be used as a supportive, placebo-based, dose-reduction strategy to improve treatment efficacy in an ongoing immunopharmacological regimen.

The fate of microcystins in the environment and challenges for monitoring.

Microcystins are secondary metabolites produced by cyanobacteria that act as hepatotoxins in higher organisms. These toxins can be altered through abiotic processes, such as photodegradation and adsorption, as well as through biological processes via metabolism and bacterial degradation. Some species of bacteria can degrade microcystins, and many other organisms metabolize microcystins into a series of conjugated products. There are toxicokinetic models used to examine microcystin uptake and elimination, which can be difficult to compare due to differences in compartmentalization and speciation. Metabolites of microcystins are formed as a detoxification mechanism, and little is known about how quickly these metabolites are formed. In summary, microcystins can undergo abiotic and biotic processes that alter the toxicity and structure of the microcystin molecule. The environmental impact and toxicity of these alterations and the metabolism of microcystins remains uncertain, making it difficult to establish guidelines for human health. Here, we present the current state of knowledge regarding the alterations microcystins can undergo in the environment.

Variations in the microcystin content of different fish species collected from a eutrophic lake.

Microcystins produced from cyanobacteria can accumulate in fish tissues. Liquid chromatography coupled with tandem quadrupole mass spectrometry (LC-MS/MS) is an attractive alternative to immunoassays for the determination of low concentrations of microcystins in tissues. Fish taken from Grand Lake St. Marys, a eutrophic lake in Ohio, USA, were analyzed for microcystin-LR in their fillets using LC-MS/MS. Of 129 fish tested for microcystins, only black crappie (Pomoxis nigromaculatus) and common carp (Cyprinus carpio) tested positive for microcystin-LR. Less than 10% of Pomoxis and 7% of Cyprinus samples contained measurable levels of microcystin-LR. Statistical analysis yielded a p-value of 0.07 between Pomoxis and the pooled results of the other four fish species. However, this comparison was complicated by the large difference in sample size between species. Further sampling in Grand Lake St. Marys for microcystin-LR would help determine if microcystin-LR exposure occurs through foodweb transfer.