Objective
To conduct a systematic review and meta‐analysis of studies that measured cytokine and chemokine levels in individuals with major depressive disorder (MDD) compared to healthy controls ...(HCs).
Method
The PubMed/MEDLINE, EMBASE, and PsycINFO databases were searched up until May 30, 2016. Effect sizes were estimated with random‐effects models.
Result
Eighty‐two studies comprising 3212 participants with MDD and 2798 HCs met inclusion criteria. Peripheral levels of interleukin‐6 (IL‐6), tumor necrosis factor (TNF)‐alpha, IL‐10, the soluble IL‐2 receptor, C‐C chemokine ligand 2, IL‐13, IL‐18, IL‐12, the IL‐1 receptor antagonist, and the soluble TNF receptor 2 were elevated in patients with MDD compared to HCs, whereas interferon‐gamma levels were lower in MDD (Hedge's g = −0.477, P = 0.043). Levels of IL‐1β, IL‐2, IL‐4, IL‐8, the soluble IL‐6 receptor (sIL‐6R), IL‐5, CCL‐3, IL‐17, and transforming growth factor‐beta 1 were not significantly altered in individuals with MDD compared to HCs. Heterogeneity was large (I2: 51.6–97.7%), and sources of heterogeneity were explored (e.g., age, smoking status, and body mass index).
Conclusion
Our results further characterize a cytokine/chemokine profile associated with MDD. Future studies are warranted to further elucidate sources of heterogeneity, as well as biosignature cytokines secreted by other immune cells.
Objective
This study aimed to systematically appraise the meta‐analyses of observational studies on risk factors and peripheral biomarkers for schizophrenia spectrum disorders.
Methods
We conducted ...an umbrella review to capture all meta‐analyses and Mendelian randomization studies that examined associations between non‐genetic risk factors and schizophrenia spectrum disorders. For each eligible meta‐analysis, we estimated the summary effect size estimate, its 95% confidence and prediction intervals and the I2 metric. Additionally, evidence for small‐study effects and excess significance bias was assessed.
Results
Overall, we found 41 eligible papers including 98 associations. Sixty‐two associations had a nominally significant (P‐value <0.05) effect. Seventy‐two of the associations exhibited large or very large between‐study heterogeneity, while 13 associations had evidence for small‐study effects. Excess significance bias was found in 18 associations. Only five factors (childhood adversities, cannabis use, history of obstetric complications, stressful events during adulthood, and serum folate level) showed robust evidence.
Conclusion
Despite identifying 98 associations, there is only robust evidence to suggest that cannabis use, exposure to stressful events during childhood and adulthood, history of obstetric complications, and low serum folate level confer a higher risk for developing schizophrenia spectrum disorders. The evidence on peripheral biomarkers for schizophrenia spectrum disorders remains limited.
The breast cancer resistance protein (BCRP, ABCG2) belongs to the superfamily of ATP binding-cassette (ABC) proteins. In addition to other physiological functions, it transports potentially ...cell-damaging compounds out of the cell using the energy from ATP hydrolysis. Certain tumors overexpressing BCRP were found to become resistant against various anticancer drugs. In previous work, we found that tariquidar analogues lacking the tetrahydroisoquinoline moiety selectively inhibit BCRP. In the present study, we synthesized 21 derivatives of the third-generation P-gp inhibitor HM30181, which is structurally related to tariquidar. The compounds were tested for their inhibitory activities against BCRP and screened against P-glycoprotein (P-gp, ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) to confirm the selectivity toward BCRP. The most potent compounds are selective toward BCRP and 2-fold more potent than the reference Ko143. Qualitative structure-activity relationship (SAR) analysis revealed that the presence of a methoxy group in the ortho or para position of at least one phenyl ring is beneficial for inhibitory activity. Furthermore, the cytotoxicity and multidrug resistance (MDR)-reversal ability of selected compounds were investigated. It was shown that they have a low cytotoxicity and the ability to reverse the BCRP-mediated SN-38 resistance.
To date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of ...meta-analyses of peripheral non-genetic biomarkers for BD.
The Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included.
Six references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of 'positive' nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I 2 ⩾ 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%.
Our findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of 'positive' results and selective reporting of outcomes are possible mechanisms.
Summary
Background
Acute thrombotic microangiopathies (TMAs) are characterized by excessive microvascular thrombosis and are associated with markers of neutrophil extracellular traps (NETs) in ...plasma. NETs are composed of DNA fibers and promote thrombus formation through the activation of platelets and clotting factors.
Objective
The efficient removal of NETs may be required to prevent excessive thrombosis such as in TMAs. To test this hypothesis, we investigated whether TMAs are associated with a defect in the degradation of NETs.
Methods and Results
We show that NETs generated in vitro were efficiently degraded by plasma from healthy donors. However, NETs remained stable after exposure to plasma from TMA patients. The inability to degrade NETs was linked to a reduced DNase activity in TMA plasma. Plasma DNase1 was required for efficient NET degradation and TMA plasma showed decreased levels of this enzyme. Supplementation of TMA plasma with recombinant human DNase1 restored NET‐degradation activity.
Conclusions
Our data indicate that DNase1‐mediated degradation of NETs is impaired in patients with TMAs. The role of plasma DNases in thrombosis is, as of yet, poorly understood. Reduced plasma DNase1 activity may cause the persistence of pro‐thrombotic NETs and thus promote microvascular thrombosis in TMA patients.
Abstract Reactive oxygen species (ROS) are highly reactive oxygen-derived chemical compounds that are by-products of aerobic cellular metabolism as well as crucial second messengers in numerous ...signaling pathways. In excitation–contraction-coupling (ECC), which links electrical signaling and coordinated cardiac contraction, ROS have a severe impact on several key ion handling proteins such as ion channels and transporters, but also on regulating proteins such as protein kinases (e.g. CaMKII, PKA or PKC), thereby pivotally influencing the delicate balance of this finely tuned system. While essential as second messengers, ROS may be deleterious when excessively produced due to a disturbed balance in Na+ and Ca 2 + handling, resulting in Na+ and Ca 2 + overload, SR Ca 2 + loss and contractile dysfunction. This may, in the end, result in systolic and diastolic dysfunction and arrhythmias. This review aims to provide an overview of the single targets of ROS in ECC and to outline the role of ROS in major cardiac pathologies, such as heart failure and arrhythmogenesis. This article is part of a Special Issue entitled “Redox Signalling in the Cardiovascular System”
UV irradiation technology as a membrane bioreactor (MBR) post-treatment was investigated and assessed. Both UV low pressure (LP) and medium pressure (MP) lamps were examined. The technology was ...installed in a pilot plant treating hospital wastewater to provide the study with adequate field data.
The effect of the UV irradiation was enhanced with varying dosages of H2O2 to establish an advanced oxidation process (AOP). The efficiency of the pharmaceutical removal process was assessed by examining 14 micropollutants (antibiotics, analgesics, anticonvulsants, beta-blockers, cytostatics and X-ray contrast media) which are typically released by hospitals and detected with liquid chromatography coupled tandem mass spectrometry (LC–MS/MS).
While the MBR treatment generally showed only a low degradation capacity for persistent pharmaceuticals, much better degradation was obtained by applying UV irradiation and H2O2 as AOP. The “conventional” cost-benefit analysis of the different technology options taking into account both electrical energy consumption and pharmaceutical removal efficiency, revealed clearly better performance of low pressure UV lamps as AOP. However, a holistic comparison between the different scenarios was carried out by evaluating their environmental impacts using the life cycle assessment (LCA) methodology. Decisive advantages were highlighted to include this approach in the decision making process.
Abstract Objective The international acceptance of a universal classification system for radical hysterectomy is one of the important challenges in gynecologic oncology. The recently published ...classification system by Querleu and Morrow is a relevant proposal that has been well received by the professional community. However, it does not include a description of parametrial resection in three dimensions, which mostly determines post-operative morbidity. Methods The intention of this follow-up paper was to further develop the classification system based on the four proposed types of radical hysterectomy (A–D) into a three-dimensional model using standard anatomical landmarks for definition of resection margins in longitudinal and transverse dimensions and demonstrate it on pictures. Results Resection margins were defined in longitudinal and transverse dimensions for each suggested type of radical hysterectomy on all three parts of the parametria. Besides precise description using stable anatomical landmarks, all resection lines have been shown on intra-operative photographs. Conclusion Four types of radical hysteretomy can be precisely defined on a three-dimensional anatomical template, including nerve sparing procedure. Our paper should contribute to better standardization (including nomenclature) of the radical hysterectomy, enhancing harmonization of clinical practice in gynecological oncology.
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