The dynamic relationship between sleep and psychotic experiences across the early stages of the psychosis continuum.

BACKGROUND: Psychotic disorders develop gradually along a continuum of severity. Understanding factors associated with psychosis development, such as sleep, could aid in identification of individuals at elevated risk. This study aimed to assess (1) the dynamic relationship between psychotic experiences (PEs) and sleep quality and quantity, and (2) whether this relationship differed between different clinical stages along the psychosis continuum. METHODS: We used daily diary data (90 days) of individuals (N = 96) at early stages (i.e. before a first diagnosis of psychosis) along the psychosis continuum. Multilevel models were constructed with sleep quality and sleep quantity as predictors of PEs and vice versa. Post-hoc, we constructed a multilevel model with both sleep quality and quantity as predictors of PEs. In addition, we tested whether associations differed between clinical stages. RESULTS: Within persons, poorer sleep predicted next day PEs (B = -0.02, p = 0.01), but not vice versa. Between persons, shorter sleep over the 90-day period predicted more PEs (B = -0.04, p = 0.002). Experiencing more PEs over 90-days predicted poorer (B = -0.02, p = 0.02) and shorter (B = -1.06, p = 0.008) sleep. We did not find any significant moderation effects for clinical stage. CONCLUSIONS: We found a bidirectional relationship between sleep and PEs with daily fluctuations in sleep predicting next day PEs and general patterns of more PEs predicting poorer and shorter sleep. Our results highlight the importance of assessing sleep as a risk marker in the early clinical stages for psychosis.

The added value of daily diary data in 1- and 3-year prediction of psychopathology and psychotic experiences in individuals at risk for psychosis.

This study aimed to assess whether adding information on psychological experiences derived from a daily diary to baseline cross-sectional data could improve short- (1-year) and long-term (3-years) prediction of psychopathology and positive psychotic experiences (PEs). We used 90-day daily diary data from 96 individuals in early subclinical risk stages for psychosis. Stepwise linear regression models were built for psychopathology and PEs at 1- and 3-years follow-up, adding: (1) baseline questionnaires, (2) the mean and variance of daily psychological experiences, and (3) individual symptom network density. We assessed whether similar results could be achieved with a subset of the data (7-14- and 30-days). The mean and variance of the diary improved model prediction of short- and long-term psychopathology and PEs, compared to prediction based on baseline questionnaires solely. Similar results were achieved with 7-14- and 30-day subsets. Symptom network density did not improve model prediction except for short-term prediction of PEs. Simple metrics, i.e., the mean and variance from 7 to 14 days of daily psychological experiences assessments, can improve short- and long-term prediction of both psychopathology and PEs in individuals in early subclinical stages for psychosis. Diary data could be a valuable addition to clinical risk prediction models for psychopathology development.

Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration.

BACKGROUND AND PURPOSE: The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, reduces hepatic steatosis and has been suggested to reduce atherosclerosis; however, its effects on liver inflammation are underexplored. Here, we tested the hypothesis that exendin-4 reduces inflammation in both the liver and vessel wall, and investigated the common underlying mechanism. EXPERIMENTAL APPROACH: Female APOE*3-Leiden.CETP mice, a model with human-like lipoprotein metabolism, were fed a cholesterol-containing Western-type diet for 5 weeks to induce atherosclerosis and subsequently treated for 4 weeks with exendin-4. KEY RESULTS: Exendin-4 modestly improved dyslipidaemia, but markedly decreased atherosclerotic lesion severity and area (-33%), accompanied by a reduction in monocyte adhesion to the vessel wall (-42%) and macrophage content in the plaque (-44%). Furthermore, exendin-4 reduced hepatic lipid content and inflammation as well as hepatic CD68⁺ (-18%) and F4/80⁺ (-25%) macrophage content. This was accompanied by less monocyte recruitment from the circulation as the Mac-1⁺ macrophage content was decreased (-36%). Finally, exendin-4 reduced hepatic chemokine expression in vivo and suppressed oxidized low-density lipoprotein accumulation in peritoneal macrophages in vitro, effects dependent on the GLP-1 receptor. CONCLUSIONS AND IMPLICATIONS: Exendin-4 reduces inflammation in both the liver and vessel wall by reducing macrophage recruitment and activation. These data suggest that exendin-4 could be a valuable strategy to treat NASH and atherosclerosis simultaneously.

Expression of the polymeric Immunoglobulin Receptor (pIgR) in mucosal tissues of common carp (Cyprinus carpio L.).

The mucosal immune system seems to be an important defence mechanism for fish but the binding of IgM in mucosal organs is poorly described in fish. In this study the gene encoding the polymeric Immunoglobulin Receptor (pIgR) in carp has been isolated and sequenced from a liver cDNA-library and aligned with other species. The pIgR of carp consists of 2 Ig domains, a transmembrane and an intracellular region, together 327 amino acids. In situ hybridisations with sense and anti-sense DIG-labelled pIgR RNA probes were performed on liver, gut and skin of common carp (Cyprinus carpio L.) and in these organs only anti-sense probes were found to hybridise. In liver the majority of hepatocytes was stained around the nucleus. In gut and skin, staining could be detected around the nucleus of the epithelial cells, but in gut also a subpopulation of lymphoid cells was stained in epithelium and lamina propria. The specific in situ hybridisation of the epithelia and hepatocytes coincides with the in situ binding of FITC-labelled carp IgM to the same cells. RT-PCR results indicate the expression of the pIgR gene in all lymphoid organs of carp, but not in muscle. Macrophages/neutrophils enriched by adherence or sorted B cells (MACS) did not show expression of the pIgR gene and are excluded as the pIgR expressing lymphoid cells in the intestine. The relevance of pIgR staining and gene expression in mucosal organs is discussed.

Mixing in liquid-impelled loop reactors.

The liquid-impelled loop reactor is a new column-type bioreactor. The design of this device is based on the principle of the air-lift loop reactor. In the external-loop configuration used in this work, descending perfluorochemical drops bring about circulation of the continuous aqueous phase. Mixing of this continuous phase is characterized per section of the reactor. Axial-dispersion coefficients for the tube with two-phase flow are determined and correlated with the energy dissipation in the tube. Comparisons with similar systems such as bubble columns and air-lift loop reactors are made. Overall mixing parameters are derived and used for calculation of the number of circulations needed to achieve a certain degree of mixing. The hydrodynamic model from previous work is tested for the reactor configurations of this work. It can be useful to calculate circulation times.