scholarly journals Depressive Symptoms After PCB Exposure: Hypotheses for Underlying Pathomechanisms via the Thyroid and Dopamine System

2019 ◽  
Vol 16 (6) ◽  
pp. 950 ◽  
Author(s):  
Petra Gaum ◽  
Monika Gube ◽  
André Esser ◽  
Thomas Schettgen ◽  
Natalia Quinete ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Homovanillic Acid ◽  
Health Surveillance ◽  
Surveillance Program ◽  
Free T4 ◽  
Dopamine System ◽  
Mixed Effect ◽  
Mixed Effect Models ◽  
The Brain ◽  
Pcb Exposure

Polychlorinated biphenyls’ (PCB) exposure has been reported to be associated with depressive symptoms, which is correlated to lower dopamine- (DA) and thyroxine-concentrations (T4). T4 is necessary for DA-synthesis and it binds to transthyretin (TTR) being transported into the brain. PCBs can displace T4 by binding to TTR itself, being transported into the brain and disturbing DA-synthesis, where depressive symptoms might occur. Consequently, the free T4-concentration (fT4) increases when PCBs bind to TTR. The interaction of PCBs with fT4 and its associations with the main DA metabolite, homovanillic acid (HVA), and depressive symptoms were investigated. In total, 116 participants (91.6% men) were investigated, who took part in three annual examinations (t1–t3) of the HELPcB health surveillance program. Blood was collected for measuring PCBs, hydroxy PCBs (OH-PCBs), and fT4 and urine for HVA. Depressive Symptoms were assessed with a standardized questionnaire. Interactions were tested cross-sectionally with multiple hierarchical regressions and longitudinally with mixed effect models. Related to HVA, an interaction was cross-sectionally found for lower-chlorinated PCBs (LPCBs) and dioxin-like PCBs (dlPCBs); longitudinally only for LPCBs. Related to depressive symptoms, the interaction was found for LPCBs, dlPCBs, and OH-PCBs; longitudinally again only for LPCBs. The results give first hints that a physiological process involving the thyroid and DA system is responsible for depressive symptoms after PCB exposure.

scholarly journals Cortical excitability signatures for the degree of sleepiness in human

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Chin-Hsuan Chia ◽  
Xin-Wei Tang ◽  
Yue Cao ◽  
Hua-Teng Cao ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Cortical Excitability ◽  
Underlying Mechanism ◽  
Self Report ◽  
Mixed Effect ◽  
Synaptic Homeostasis ◽  
Mixed Effect Models ◽  
Physiological Homeostasis ◽  
The Relationship ◽  
The Brain ◽  
Homeostasis Theory

Sleep is essential in maintaining physiological homeostasis in the brain. While the underlying mechanism is not fully understood, a 'synaptic homeostasis' theory has been proposed that synapses continue to strengthen during awake, and undergo downscaling during sleep. This theory predicts that brain excitability increases with sleepiness. Here, we collected transcranial magnetic stimulation (TMS) measurements in 38 subjects in a 34-hour program, and decoded the relationship between cortical excitability and self-report sleepiness using advanced statistical methods. By utilizing a combination of partial least squares (PLS) regression and mixed-effect models, we identified a robust pattern of excitability changes, which can quantitatively predict the degree of sleepiness. Moreover, we found that synaptic strengthen occurred in both excitatory and inhibitory connections after sleep deprivation. In sum, our study provides supportive evidence for the synaptic homeostasis theory in human sleep and clarifies the process of synaptic strength modulation during sleepiness.

scholarly journals Fast and Powerful Genome Wide Association Analysis of Dense Genetic Data with High Dimensional Imaging Phenotypes

2017 ◽  
Author(s):  
Habib Ganjgahi ◽  
Anderson M. Winkler ◽  
David C. Glahn ◽  
John Blangero ◽  
Brian Donohue ◽  
...  
Keyword(s):  
Mixed Models ◽  
Multiple Testing ◽  
Genetic Basis ◽  
Genome Wide Association ◽  
High Dimensional ◽  
Mixed Effect ◽  
Mixed Effect Models ◽  
Genome Wide ◽  
The Brain ◽  
Linear Mixed Effect Models

ABSTRACTGenome wide association (GWA) analysis of brain imaging phenotypes can advance our understanding of the genetic basis of normal and disorder-related variation in the brain. GWA approaches typically use linear mixed effect models to account for non-independence amongst subjects due to factors such as family relatedness and population structure. The use of these models with high-dimensional imaging phenotypes presents enormous challenges in terms of computational intensity and the need to account multiple testing in both the imaging and genetic domain. Here we present method that makes mixed models practical with high-dimensional traits by a combination of a transformation applied to the data and model, and the use of a non-iterative variance component estimator. With such speed enhancements permutation tests are feasible, which allows inference on powerful spatial tests like the cluster size statistic.

scholarly journals Pain and the Emotional Brain: Affective Rather than Cognitive Processes Drive the Cortical Encoding of Pain

2021 ◽  
Author(s):  
Astrid Mayr ◽  
Anne Stankewitz ◽  
Stephanie Irving ◽  
Viktor Witkovsky ◽  
Enrico Schulz
Keyword(s):  
Pain Intensity ◽  
Cognitive Processes ◽  
The Body ◽  
Cold Pain ◽  
Mixed Effect ◽  
Mixed Effect Models ◽  
Motivational Aspect ◽  
Pain Ratings ◽  
The Brain ◽  
Linear Mixed Effect Models

The experience of pain has been dissociated into two interwoven aspects: a sensory-discriminative aspect assessed in ratings of pain intensity and an affective-motivational aspect assessed in ratings of unpleasantness. In a pain attenuation paradigm, participants were asked to evaluate applied cold pain. The majority of the trials showed a distinct rating: Some trials were rated higher for unpleasantness, others were rated higher for intensity. Using linear mixed effect models on single trials, we related the variable difference between unpleasantness and intensity ratings to functional MRI data. The direct comparison revealed a stronger relationship between cortical data and pain ratings for unpleasantness. No region showed a stronger effect for pain intensity. The present study underlines the importance of the emotional-affective aspects of pain-related cortical processes in the brain. These findings reflect the biological function of the pain system to prevent harm and to preserve the physical integrity of the body.

Polychlorinated biphenyl induced hepatocyte alterations

1987 ◽  
Vol 45 ◽  
pp. 716-717
Author(s):  
D.N. Collins ◽  
J.N. Turner ◽  
K.O. Brosch ◽  
R.F. Seegal
Keyword(s):  
Lipid Droplets ◽  
Wistar Rats ◽  
Homovanillic Acid ◽  
Polychlorinated Biphenyl ◽  
Corn Oil ◽  
Environmental Pollutants ◽  
Short Term ◽  
Pcb Congeners ◽  
Urinary Levels ◽  
The Brain

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).

scholarly journals A hierarchical bivariate meta-analysis of diagnostic test accuracy to provide direct comparisons of immunoassays vs. indirect immunofluorescence for initial screening of connective tissue diseases

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Michelle Elaine Orme ◽  
Carmen Andalucia ◽  
Sigrid Sjölander ◽  
Xavier Bossuyt
Keyword(s):  
Connective Tissue ◽  
Indirect Immunofluorescence ◽  
Meta Analysis ◽  
Connective Tissue Diseases ◽  
Test Accuracy ◽  
Initial Screening ◽  
Case Control Studies ◽  
Cross Sectional ◽  
Mixed Effect ◽  
Mixed Effect Models

AbstractObjectivesTo compare indirect immunofluorescence (IIF) for antinuclear antibodies (ANA) against immunoassays (IAs) as an initial screening test for connective tissue diseases (CTDs).MethodsA systematic literature review identified cross-sectional or case-control studies reporting test accuracy data for IIF and enzyme-linked immunosorbent assays (ELISA), fluorescence enzyme immunoassay (FEIA), chemiluminescent immunoassay (CLIA) or multiplex immunoassay (MIA). The meta-analysis used hierarchical, bivariate, mixed-effect models with random-effects by test.ResultsDirect comparisons of IIF with ELISA showed that both tests had good sensitivity (five studies, 2321 patients: ELISA: 90.3% [95% confidence interval (CI): 80.5%, 95.5%] vs. IIF at a cut-off of 1:80: 86.8% [95% CI: 81.8%, 90.6%]; p = 0.4) but low specificity, with considerable variance across assays (ELISA: 56.9% [95% CI: 40.9%, 71.5%] vs. IIF 1:80: 68.0% [95% CI: 39.5%, 87.4%]; p = 0.5). FEIA sensitivity was lower than IIF sensitivity (1:80: p = 0.005; 1:160: p = 0.051); however, FEIA specificity was higher (seven studies, n = 12,311, FEIA 93.6% [95% CI: 89.9%, 96.0%] vs. IIF 1:80 72.4% [95% CI: 62.2%, 80.7%]; p < 0.001; seven studies, n = 3251, FEIA 93.5% [95% CI: 91.1%, 95.3%] vs. IIF 1:160 81.1% [95% CI: 73.4%, 86.9%]; p < 0.0001). CLIA sensitivity was similar to IIF (1:80) with higher specificity (four studies, n = 1981: sensitivity 85.9% [95% CI: 64.7%, 95.3%]; p = 0.86; specificity 86.1% [95% CI: 78.3%, 91.4%]). More data are needed to make firm inferences for CLIA vs. IIF given the wide prediction region. There were too few studies for the meta-analysis of MIA vs. IIF (MIA sensitivity range 73.7%–86%; specificity 53%–91%).ConclusionsFEIA and CLIA have good specificity compared to IIF. A positive FEIA or CLIA test is useful to support the diagnosis of a CTD. A negative IIF test is useful to exclude a CTD.

scholarly journals Neurophysiological and behavioural effects of conventional and high definition tDCS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fabio Masina ◽  
Giorgio Arcara ◽  
Eleonora Galletti ◽  
Isabella Cinque ◽  
Luciano Gamberini ◽  
...  
Keyword(s):  
Response Times ◽  
Power Reduction ◽  
Alpha Power ◽  
High Definition ◽  
Mixed Effect ◽  
State Dependency ◽  
Mixed Effect Models ◽  
Beta Power ◽  
Neurophysiological Data ◽  
Spectrum Density

AbstractHigh-definition transcranial direct current stimulation (HD-tDCS) seems to overcome a drawback of traditional bipolar tDCS: the wide-spread diffusion of the electric field. Nevertheless, most of the differences that characterise the two techniques are based on mathematical simulations and not on real, behavioural and neurophysiological, data. The study aims to compare a widespread tDCS montage (i.e., a Conventional bipolar montage with extracephalic return electrode) and HD-tDCS, investigating differences both at a behavioural level, in terms of dexterity performance, and a neurophysiological level, as modifications of alpha and beta power as measured with EEG. Thirty participants took part in three sessions, one for each montage: Conventional tDCS, HD-tDCS, and sham. In all the conditions, the anode was placed over C4, while the cathode/s placed according to the montage. At baseline, during, and after each stimulation condition, dexterity was assessed with a Finger Tapping Task. In addition, resting-state EEG was recorded at baseline and after the stimulation. Power spectrum density was calculated, selecting two frequency bands: alpha (8–12 Hz) and beta (18–22 Hz). Linear mixed effect models (LMMs) were used to analyse the modulation induced by tDCS. To evaluate differences among the montages and consider state-dependency phenomenon, the post-stimulation measurements were covariate-adjusted for baseline levels. We observed that HD-tDCS induced an alpha power reduction in participants with lower alpha at baseline. Conversely, Conventional tDCS induced a beta power reduction in participants with higher beta at baseline. Furthermore, data showed a trend towards a behavioural effect of HD-tDCS in participants with lower beta at baseline showing faster response times. Conventional and HD-tDCS distinctively modulated cortical activity. The study highlights the importance of considering state-dependency to determine the effects of tDCS on individuals.

scholarly journals Recombining Your Way Out of Trouble: The Genetic Architecture of Hybrid Fitness under Environmental Stress

2019 ◽  
Vol 37 (1) ◽  
pp. 167-182 ◽  
Author(s):  
Zebin Zhang ◽  
Devin P Bendixsen ◽  
Thijs Janzen ◽  
Arne W Nolte ◽  
Duncan Greig ◽  
...  
Keyword(s):  
Environmental Stress ◽  
Evolutionary Potential ◽  
Genetic Trait ◽  
Hybrid Fitness ◽  
Mixed Effect ◽  
Mixed Effect Models ◽  
Hybrid Genome ◽  
Chromosome Associations ◽  
Low Coverage ◽  
Negative Epistasis

Abstract Hybridization between species can either promote or impede adaptation. But we know very little about the genetic basis of hybrid fitness, especially in nondomesticated organisms, and when populations are facing environmental stress. We made genetically variable F2 hybrid populations from two divergent Saccharomyces yeast species. We exposed populations to ten toxins and sequenced the most resilient hybrids on low coverage using ddRADseq to investigate four aspects of their genomes: 1) hybridity, 2) interspecific heterozygosity, 3) epistasis (positive or negative associations between nonhomologous chromosomes), and 4) ploidy. We used linear mixed-effect models and simulations to measure to which extent hybrid genome composition was contingent on the environment. Genomes grown in different environments varied in every aspect of hybridness measured, revealing strong genotype–environment interactions. We also found selection against heterozygosity or directional selection for one of the parental alleles, with larger fitness of genomes carrying more homozygous allelic combinations in an otherwise hybrid genomic background. In addition, individual chromosomes and chromosomal interactions showed significant species biases and pervasive aneuploidies. Against our expectations, we observed multiple beneficial, opposite-species chromosome associations, confirmed by epistasis- and selection-free computer simulations, which is surprising given the large divergence of parental genomes (∼15%). Together, these results suggest that successful, stress-resilient hybrid genomes can be assembled from the best features of both parents without paying high costs of negative epistasis. This illustrates the importance of measuring genetic trait architecture in an environmental context when determining the evolutionary potential of genetically diverse hybrid populations.

Association of fine particulate matter with glucose and lipid metabolism: a longitudinal study in young adults

2021 ◽  
pp. oemed-2020-107039
Author(s):  
Jingyi Qin ◽  
Wei Xia ◽  
Gaodao Liang ◽  
Shunqing Xu ◽  
Xiuge Zhao ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Lipid Metabolism ◽  
Longitudinal Study ◽  
Fine Particulate Matter ◽  
Healthy Adults ◽  
Mixed Effect ◽  
Glucose And Lipid Metabolism ◽  
Mixed Effect Models ◽  
Fine Particulate ◽  
Linear Mixed Effect Models

ObjectivesThis study aimed to evaluate whether PM2.5 exposure in a highly polluted area (>100 µg/m3) affects glucose and lipid metabolism in healthy adults.MethodsWe recruited 110 healthy adults in Baoding city, Hebei, China, and followed them up between 2017 and 2018. Personal air samplers were used to monitor personal PM2.5 levels. Eight glucose and lipid metabolism parameters were quantified. We performed the linear mixed-effect models to investigate the relationships between PM2.5 and glucose and lipid metabolism parameters. Stratified analyses were further performed according to sex and body mass index (BMI).ResultsThe concentration of PM2.5 was the highest in spring, with a median of 232 μg/m3 and the lowest in autumn (139 μg/m3). After adjusting for potential confounders, we found that for each twofold increase in PM2.5, the median of insulin concentration decreased by 5.89% (95% CI −10.91% to −0.58%; p<0.05), and ox-LDL increased by 6.43% (95% CI 2.21% to 10.82%; p<0.05). Stratified analyses indicated that the associations were more pronounced in females, overweight and obese participants.ConclusionsExposure to high PM2.5 may have deleterious effects on glucose and lipid metabolism. Females, overweight and obese participants are more vulnerable.

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