Cumulative meta-analysis of interleukins 6 and 1β, tumour necrosis factor α and C-reactive protein in patients with major depressive disorder

Cumulative meta-analyses are used to evaluate the extent to which further studies are needed to confirm or refute a hypothesis. We used this approach to assess observational evidence on systemic inflammation in individuals with major depressive disorder. We identified 58 studies of four common inflammatory markers in a literature search of PubMed, Embase and PsychInfo databases in May 2014. Pooled data from the earliest eight studies already showed an association between interleukin-6 concentrations and major depression; 23 more recent studies confirmed this finding (d=0.54, p<0.0001). A significant association between C-reactive protein levels and major depression was noted after 14 studies and this did not change after addition of six more studies (d=0.47, p<0.0001). For these two inflammatory markers, there was moderate heterogeneity in study-specific estimates, subgroup differences were small, and publication bias appeared to be an unlikely explanation for the findings. Sensitivity analyses including only high-quality studies and subjects free of antidepressant medication further verified the associations. While there was a link between tumour necrosis factor-α levels and major depression (d=0.40, p=0.002), the cumulative effect remained uncertain due to the extensive heterogeneity in study-specific estimates and inconsistencies between subgroups. No evidence was found for the association between interleukin-1β levels and major depression (d=-0.05, p=0.86). In conclusion, this cumulative meta-analysis confirmed higher mean levels of interleukin-6 and C-reactive protein in patients with major depression compared to non-depressed controls. No consistent association between tumour necrosis factor-α, interleukin-1β and major depression was observed. Future studies should clarify the specific immune mechanisms involved as well as continue testing anti-inflammatory therapies in patients suffering from major depression

Graphene oxide elicits microbiome-dependent type 2 immune responses via the aryl hydrocarbon receptor

The gut microbiome produces metabolites that interact with the aryl hydrocarbon receptor (AhR), a key regulator of immune homoeostasis in the gut(1,2). Here we show that oral exposure to graphene oxide (GO) modulates the composition of the gut microbiome in adult zebrafish, with significant differences in wild-type versus ahr2-deficient animals. Furthermore, GO was found to elicit AhR-dependent induction of cyp1a and homing of lck(+) cells to the gut in germ-free zebrafish larvae when combined with the short-chain fatty acid butyrate. To obtain further insights into the immune responses to GO, we used single-cell RNA sequencing to profile cells from whole germ-free embryos as well as cells enriched for lck. These studies provided evidence for the existence of innate lymphoid cell (ILC)-like cells(3) in germ-free zebrafish. Moreover, GO endowed with a 'corona' of microbial butyrate triggered the induction of ILC2-like cells with attributes of regulatory cells. Taken together, this study shows that a nanomaterial can influence the crosstalk between the microbiome and immune system in an AhR-dependent manner.Peer reviewe

Hedgehog-mediated gut-taste neuron axis controls sweet perception in Drosophila

Dietary composition affects food preference in animals. High sugar intake suppresses sweet sensation from insects to humans, but the molecular basis of this suppression is largely unknown. Here, we reveal that sugar intake in Drosophila induces the gut to express and secrete Hedgehog (Hh) into the circulation. We show that the midgut secreted Hh localize to taste sensilla and suppresses sweet sensation, perception, and preference. We further find that the midgut Hh inhibits Hh signalling in the sweet taste neurons. Our electrophysiology studies demonstrate that the midgut Hh signal also suppresses bitter taste and some odour responses, affecting overall food perception and preference. We further show that the level of sugar intake during a critical window early in life, sets the adult gut Hh expression and sugar perception. Our results together reveal a bottom-up feedback mechanism involving a “gut-taste neuron axis” that regulates food sensation and preference

Inhalation exposure to nanosized and fine TiO2 particles inhibits features of allergic asthma in a murine model

<p>Abstract</p> <p>Background</p> <p>Nanotechnology and engineered nanomaterials (ENM) are here to stay. Recent evidence suggests that exposure to environmental particulate matter exacerbates symptoms of asthma. In the present study we investigated the modulatory effects of titanium dioxide particle exposure in an experimental allergic asthma.</p> <p>Methods</p> <p>Nonallergic (healthy) and ovalbumin-sensitized (asthmatic) mice were exposed via inhalation to two different sizes of titanium dioxide particles, nanosized (nTiO₂) and fine (fTiO₂), for 2 hours a day, three days a week, for four weeks at a concentration of 10 mg/m³. Different endpoints were analysed to evaluate the immunological status of the mice.</p> <p>Results</p> <p>Healthy mice elicited pulmonary neutrophilia accompanied by significantly increased chemokine CXCL5 expression when exposed to nTiO₂. Surprisingly, allergic pulmonary inflammation was dramatically suppressed in asthmatic mice which were exposed to nTiO₂or fTiO₂particles - i.e. the levels of leucocytes, cytokines, chemokines and antibodies characteristic to allergic asthma were substantially decreased.</p> <p>Conclusions</p> <p>Our results suggest that repeated airway exposure to TiO₂particles modulates the airway inflammation depending on the immunological status of the exposed mice.</p

Education-Based Cutoffs for Cognitive Screening of Alzheimer’s Disease

Introduction: The educational background and size of the elderly population are undergoing significant changes in Finland during the 2020s. A similar process is likely to occur also in several European countries. For cognitive screening of early Alzheimer’s disease (AD), using outdated norms and cutoff scores may negatively affect clinical accuracy. The aim of the present study was to examine the effects of education, age, and gender on the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery (CERAD-nb) in a large register-based, clinical sample of patients with mild AD and nondemented at-risk persons from the general population (controls) and to examine whether corrected cutoff scores would increase the accuracy of differentiation between the 2 groups. Methods: CERAD-nb scores were obtained from AD patients (n = 389, 58% women, mean age 74.0 years) and from controls (n = 1,980, 52% women, mean age 68.5 years). The differences in CERAD-nb performance were evaluated by univariate GLM. Differentiation between the 2 groups was evaluated using a receiver operating characteristic (ROC) curve, where a larger area under the ROC curve represents better discrimination. Youden’s J was calculated for the overall performance and accuracy of each of the measures. Results: Of the demographic factors, education was the strongest predictor of CERAD-nb performance, explaining more variation than age or gender in both the AD patients and the controls. Education corrected cutoff scores had better diagnostic accuracy in discriminating between the AD patients and controls than existing uncorrected scores. The highest level of discrimination between the 2 groups overall was found for two CERAD-nb total scores. Conclusions: Education-corrected cutoff scores were superior to uncorrected scores in differentiating between controls and AD patients especially for the highest level of education and should therefore be used in clinical cognitive screening, also as the proportion of the educated elderly is increasing substantially during the 2020s. Our results also indicate that total scores of the CERAD-nb are better at discriminating AD patients from controls than any single subtest score. A digital tool for calculating the total scores and comparing education-based cutoffs would increase the efficiency and usability of the test.Peer reviewe

Spatial structure of the 8200 cal yr BP event in northern Europe

International audienceA synthesis of well-dated high-resolution pollen records suggests a spatial structure in the 8200 cal yr BP event in northern Europe. The temperate, thermophilous tree taxa, especially Corylus, Ulmus, and Alnus, decline abruptly between 8300 and 8000 cal yr BP at most sites located south of 61° N, whereas there is no clear change in pollen values at the sites located in the North-European tree-line region. Pollen-based quantitative temperature reconstructions and several other, independent palaeoclimate proxies, such as lacustrine oxygen-isotope records, reflect the same pattern, with no detectable cooling in the sub-arctic region. The observed patterns challenges the general view of the wide-spread occurrence of the 8200 cal yr BP event in the North Atlantic region. An alternative explanation is that the cooling during the 8200 cal yr BP event took place mostly during the winter and spring, and the ecosystems in the south responded sensitively to the cooling during the onset of the growing season. In contrast, in the sub-arctic area, where the vegetation was still dormant and lakes ice-covered, the cold event is not reflected in pollen-based or lake-sediment-based records

Cognitive Performance at Time of AD Diagnosis : A Clinically Augmented Register-Based Study

We aimed to evaluate the feasibility of using real-world register data for identifying persons with mild Alzheimer's disease (AD) and to describe their cognitive performance at the time of diagnosis. Patients diagnosed with AD during 2010-2013 (aged 60-81 years) were identified from the Finnish national health registers and enlarged with a smaller private sector sample (total n = 1,268). Patients with other disorders impacting cognition were excluded. Detailed clinical and cognitive screening data (the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery [CERAD-nb]) were obtained from local health records. Adequate cognitive data were available for 389 patients with mild AD (31%) of the entire AD group. The main reasons for not including patients in analyses of cognitive performance were AD diagnosis at a moderate/severe stage (n = 266, 21%), AD diagnosis given before full register coverage (n = 152, 12%), and missing CERAD-nb data (n = 139, 11%). The cognitive performance of persons with late-onset AD (n = 284), mixed cerebrovascular disease and AD (n = 51), and other AD subtypes (n = 54) was compared with that of a non-demented sample (n = 1980) from the general population. Compared with the other AD groups, patients with late-onset AD performed the worst in word list recognition, while patients with mixed cerebrovascular disease and AD performed the worst in constructional praxis and clock drawing tests. A combination of national registers and local health records can be used to collect data relevant for cognitive screening; today, the process is laborious, but it could be improved in the future with refined search algorithms and electronic data.Peer reviewe

Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity

The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as 2 days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, desilencing chromatin-state-defined domains in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3-dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution

Review of the Commission Decision 2010/477/EU concerning MSFD criteria for assessing Good Environmental Status, Descriptor 7

This report represents the result of the scientific and technical review of Commission Decision 2010/477/EU in relation to Descriptor 7. The review has been carried out by the EC JRC together with experts nominated by EU Member States, and has considered contributions from the GES Working Group in accordance with the roadmap set out in the MSFD implementation strategy (agreed on at the 11th CIS MSCG meeting). The report is one of a series of reports (review manuals) including Descriptor 1, 2, 5, 7, 8, 9, 10 that conclude phase 1 of the review process and, as agreed within the MSFD Common Implementation Strategy, are the basis for review phase 2, towards an eventual revision of the Commission Decision 2010/477/EU. The report presents the state of the technical discussions as of 30 April 2015 (document version 7.0: ComDecRev_D7_V7.0_FINAL.docx), as some discussions are ongoing, it does not contain agreed conclusions on all issues. The document does not represent an official, formal position of any of the Member States and the views expressed in the document are not to be taken as representing the views of the European Commission.JRC.H.1-Water Resource