Objective
To perform a meta‐analysis on studies reporting prevalence of Toxoplasma gondii (T. gondii) infection in any psychiatric disorder compared with healthy controls. Our secondary objective was ...to analyze factors possibly moderating heterogeneity.
Method
A systematic search was performed to identify studies into T. gondii infection for all major psychiatric disorders versus healthy controls. Methodological quality, publication bias, and possible moderators were assessed.
Results
A total of 2866 citations were retrieved and 50 studies finally included. Significant odds ratios (ORs) with IgG antibodies were found in schizophrenia (OR 1.81, P < 0.00001), bipolar disorder (OR 1.52, P = 0.02), obsessive–compulsive disorder (OR 3.4, P < 0.001), and addiction (OR 1.91, P < 0.00001), but not for major depression (OR 1.21, P = 0.28). Exploration of the association between T. gondii and schizophrenia yielded a significant effect of seropositivity before onset and serointensity, but not IgM antibodies or gender. The amplitude of the OR was influenced by region and general seroprevalence. Moderators together accounted for 56% of the observed variance in study effects. After controlling for publication bias, the adjusted OR (1.43) in schizophrenia remained significant.
Conclusion
These findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia reactivation of latent T. gondii infection may occur.
Three phenotypes of adult‐onset asthma Amelink, M.; Nijs, S. B.; Groot, J. C. ...
Allergy (Copenhagen),
20/May , Letnik:
68, Številka:
5
Journal Article
Recenzirano
Rationale
Adult‐onset asthma differs from childhood‐onset asthma in many respects. It is more heterogeneous, often severe and frequently associated with loss of lung function. To identify underlying ...mechanisms of adult‐onset asthma and to capture predictors of disease progression, detailed characterization and phenotyping is necessary.
Objectives
To characterize adult‐onset asthma and identify subphenotypes of adult‐onset asthma.
Methods
A cohort of 200 patients with adult‐onset (>18 year) asthma (age 54 (26–75) year) was recruited from one academic and three nonacademic pulmonary outpatient clinics in Amsterdam, the Netherlands. These patients were fully characterized with respect to clinical, functional and inflammatory markers. After data reduction, K‐means nonhierarchical cluster analysis was performed to identify clusters of adult‐onset asthma.
Measurements and main results
Patients with adult‐onset asthma were predominately female (61%) and nonatopic (55%). Within this group of patients were identified three clusters of adult‐onset asthma. Cluster 1 (n = 69) consisted of patients with severe eosinophilic inflammation‐predominant asthma and persistent airflow limitation despite high‐intensity anti‐inflammatory treatment, with relatively low symptom scores. The second cluster was characterized by obese women with frequent symptoms, high healthcare utilization and low sputum eosinophils. The third cluster consisted of patients with mild‐to‐moderate, well‐controlled asthma with normal lung function and low inflammatory markers. Repeatability accuracy was 98.2%.
Conclusions
Amongst patients with adult‐onset asthma, three subphenotypes can be identified with distinct clinical and inflammatory characteristics. These subphenotypes help to understand the underlying pathobiology and provide clinicians with directions for personalized management.
Climate models predict increasing amounts of precipitation and relative atmospheric humidity for high latitudes in the Northern Hemisphere. Therefore, tree species must adjust to the new climatic ...conditions. We studied young silver birches (Betula pendula Roth) in a long-term (2012–2018) free air humidity manipulation experiment, with the aim of clarifying the acclimation mechanisms to elevated relative atmospheric humidity. In 2016–2018, stem radial increment (measured by dendrometers) and leaf abscission were monitored, and the leaf N and P resorption efficiencies were determined. Biomass allocation was estimated, and the seasonal dynamics of foliar NPK storage was assessed. Humidification increased N resorption efficiency by 11%. The annual means of N resorption efficiency varied from 41 to 52% in control and from 50 to 59% in humidified stands. The P resorption efficiency was strongly affected by weather conditions and varied between years from 25 to 66%. Higher foliar NPK storages at the end of growing season and delayed leaf fall allowed to extend the growth period in humidified plots, which resulted in a week longer stem radial growth. Although stem diameter growth of humidified birches recovered after 5 years, tree height retardation persisted over the seven study years, resulting in increased stem taper (diameter to height ratio) under humidification. Additionally, humidification increased the share of the bark in stem biomass and the number of branches per crown length. The acclimation of silver birches to increased air humidity entails changes in forest N cycle and in birch timber quality.
There is strong circumstantial evidence that certain heavy, unstable atomic nuclei are 'octupole deformed', that is, distorted into a pear shape. This contrasts with the more prevalent rugby-ball ...shape of nuclei with reflection-symmetric, quadrupole deformations. The elusive octupole deformed nuclei are of importance for nuclear structure theory, and also in searches for physics beyond the standard model; any measurable electric-dipole moment (a signature of the latter) is expected to be amplified in such nuclei. Here we determine electric octupole transition strengths (a direct measure of octupole correlations) for short-lived isotopes of radon and radium. Coulomb excitation experiments were performed using accelerated beams of heavy, radioactive ions. Our data on (220)Rn and (224)Ra show clear evidence for stronger octupole deformation in the latter. The results enable discrimination between differing theoretical approaches to octupole correlations, and help to constrain suitable candidates for experimental studies of atomic electric-dipole moments that might reveal extensions to the standard model.
Corticosteroids have been associated with an increased risk of venous thromboembolism in patients treated for inflammatory diseases. It is unclear whether the thrombotic risk is induced by the ...inflammation of the underlying inflammatory diseases or whether corticosteroids are prothrombotic as well. Considering the widespread use of corticosteroids in clinical practise, it is critical to know whether corticosteroids enhance coagulation.
To investigate whether a 10-day prednisolone burst therapy activates hemostasis in healthy individuals.
Healthy subjects received either 0.5 mg kg(-1) day(-1) of oral prednisolone or placebo. Venous blood was collected at baseline, day 1 and day 10 and tested for thrombin-antithrombin complexes (TATc), D-dimer, plasmin-alpha2-antiplasmin complexes (PAPc), plasminogen-activator inhibitor type-1 (PAI-1), von Willebrand factor (VWF) and thrombin generation (peak thrombin, velocity index and endogenous thrombin potential ETP).
Fifteen subjects received prednisolone and 16 placebo (median age 29 vs. 22 years, female subjects 33% vs. 56%, respectively). Peak thrombin and velocity index were higher in the placebo group at baseline. After 10 days of treatment, peak thrombin, velocity index, PAI-1 and VWF increased in the oral prednisolone group as compared with the placebo group (15.8 SD 16.3 vs. -0.1 SD 16.1, 41.2 SD 41.3 vs. -2.3 SD 42.7, 18.0 IQR 8.0-37.0 vs. 0.5 IQR -18.5-13.0, 4.0 IQR -1.0-12.0 vs. 0.0 IQR -2.5-1.5, respectively). No changes were observed for TATc, ETP, PAPc and D-dimer.
Oral prednisolone induces a procoagulant state in healthy subjects, suggesting that corticosteroid treatment may increase the thromboembolic risk in patients with inflammatory diseases.
Summary
Background
Asthma is a chronic inflammatory airway disease, associated with episodes of exacerbations. Therapy with inhaled corticosteroids (ICS) targets airway inflammation, which aims to ...maintain and restore asthma control. Clinical features are only modestly associated with airways inflammation. Therefore, we hypothesized that exhaled volatile metabolites identify longitudinal changes between clinically stable episodes and loss of asthma control.
Objectives
To determine whether exhaled volatile organic compounds (VOCs) as measured by gas‐chromatography/mass‐spectrometry (GC/MS) and electronic nose (eNose) technology discriminate between clinically stable and unstable episodes of asthma.
Methods
Twenty‐three patients with (partly) controlled mild to moderate persistent asthma using ICS were included in this prospective steroid withdrawal study. Exhaled metabolites were measured at baseline, during loss of control and after recovery. Standardized sampling of exhaled air was performed, after which samples were analysed by GC/MS and eNose. Univariate analysis of covariance (ANCOVA), followed by multivariate principal component analysis (PCA) was used to reduce data dimensionality. Next paired t tests were utilized to analyse within‐subject breath profile differences at the different time‐points. Finally, associations between exhaled metabolites and sputum inflammation markers were examined.
Results
Breath profiles by eNose showed 95% (21/22) correct classification for baseline vs loss of control and 86% (19/22) for loss of control vs recovery. Breath profiles using GC/MS showed accuracies of 68% (14/22) and 77% (17/22) for baseline vs loss of control and loss of control vs recovery, respectively. Significant associations between exhaled metabolites captured by GC/MS and sputum eosinophils were found (Pearson r≥.46, P<.01).
Conclusions & Clinical Relevance
Loss of asthma control can be discriminated from clinically stable episodes by longitudinal monitoring of exhaled metabolites measured by GC/MS and particularly eNose. Part of the uncovered biomarkers was associated with sputum eosinophils. These findings provide proof of principle for monitoring and identification of loss of asthma control by breathomics.
Background
The in vivo levels of inflammatory mediators in chronic atopic dermatitis (AD) skin are not well‐defined due to the lack of a non‐invasive or minimally invasive sampling technique.
...Objectives
To investigate the cytokine milieu in interstitial fluid (ISF) collected from chronic lesional AD skin as compared to ISF from non‐lesional AD skin and/or healthy donor skin.
Methods
ISF was obtained using a minimally invasive technique of creating micropores in the skin by a laser, and harvesting ISF through aspiration. We determined the levels of 33 cytokines by Luminex and ELISA in ISF and plasma from sixteen AD patients and twelve healthy individuals. In seven AD patients, we analysed the IL‐13, IL‐31, IL‐17, IL‐22 and IFN‐γ production by T cells isolated from lesional skin. AD patients were genotyped for the filaggrin gene (FLG)‐null mutations 2282del4, R501X, R2447X and S3247X.
Results
Twenty‐five of 33 examined mediators were detected in the ISF. The levels of IL‐1α, IL‐1β, IL‐18, IL‐1RA, IL‐5, IL‐13, IL‐6, IL‐8, TNF‐α, RANTES(CCL‐5), MIG(CXCL‐9), IP‐10(CXCL‐10), TARC(CCL‐17), VEGF and G‐CSF showed significant differences between either lesional, non‐lesional and/or healthy skin. IP‐10 levels in ISF from lesional and non‐lesional AD skin showed significant correlation with IP‐10 blood levels. IP‐10 also showed a significant correlation with clinical severity (SCORAD), as did IL‐13. Levels of both IP‐10 and IL‐13 were more pronounced in patients with FLG‐null mutations. Furthermore, FLG‐null mutation carriers had more severe AD.
Conclusion
The presented minimally invasive technique is a valuable tool to determine the in vivo cytokine profile of AD skin.
Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact ...mechanism of inflammatory response is unknown. Here, we investigated the effect of maintenance macrolide treatment on the inflammatory response in BE. In addition, we assessed the inflammatory profile in BE in relation to disease severity.
During the BAT randomized controlled trial (investigating the effect of 1 year of azithromycin (AZM) in 83 BE patients), data on BE severity, lung function and sputum microbiology was collected. For the current study, a wide range of inflammatory markers were analysed in 3- monthly sputum samples in all participants.
At baseline, marked neutrophilic but also eosinophilic inflammation was present in both groups, which remained stable throughout the study and was not affected by AZM treatment. Significant upregulation of pro-inflammatory markers correlated with FEV
< 50% (TNFα, ECP, IL-21, IL-1, p = 0.01- 0.05), H. influenzae (HI) colonization (MPO, ECP, MIP-1, TNFα, IL-21, Il-8, IL-1, IL-1α, p < 0.001 - 0.04) and number of exacerbations (MPO, ECP, VEGF, MMP-9, p = 0.003 - 0.01). Surprisingly, colonization with P. aeruginosa (PA) was found to correlate with an attenuated inflammatory response compared to non-PA colonized. In placebo-treated patients, presence of an infectious exacerbation was reflected by a significant excessive increase in inflammation as compared to a non-significant upregulation in the AZM-treated patients.
One year of AZM treatment did not result in attenuation of the inflammatory response in BE. Increasing disease severity and the presence of an exacerbation were reflected by upregulation of pro-inflammatory markers.