Kahnkloster9624

Altered brain responses to alcohol-associated stimuli are a neural hallmark of alcohol-use disorder (AUD) and a promising target for pharmacotherapy. However, findings in cue-reactivity based functional MRI (fMRI) studies are inconclusive. To investigate the neural substrates of cue-reactivity and their relevance to treatment outcomes, alcohol craving and relapse in AUD patients, we performed five meta-analyses using signed differential mapping software. Our meta-analysis revealed that alcohol cues evoke greater cue-reactivity than neutral cues in the mesocorticolimbic circuit and lower reactivity in the parietal and temporal regions in AUD patients. Compared to controls, AUD individuals displayed hyperactivations in the medial prefrontal cortex and anterior/middle part of the cingulate cortex. After receiving AUD treatment, AUD patients exhibited greater activations in the precentral gyrus but reduced activations in the bilateral caudate nucleus, insula, right DLPFC, and left superior frontal gyrus. No significant results were found in cue-reactivity correlates of alcohol craving and relapse. Our results implicate cue-induced abnormalities in corticostriatal-limbic circuits may underline the pathophysiology of AUD, and have translational value for treatment development.Visual hallucinations (VH) are common in Parkinson's disease and dementia with Lewy bodies, two forms of Lewy body disease (LBD), but the neural substrates and mechanisms involved are still unclear. We conducted meta-analyses of voxel-based morphometry (VBM) and neuropsychological studies investigating the neuroanatomical and cognitive correlates of VH in LBD. For VBM (12 studies), we used Seed-based d Mapping with Permutation of Subject Images (SDM-PSI), including statistical parametric maps for 50% of the studies. For neuropsychology (35 studies), we used MetaNSUE to consider non-statistically significant unreported effects. VH were associated with smaller grey matter volume in occipital, frontal, occipitotemporal, and parietal areas (peak Hedges' g -0.34 to -0.49). In patients with Parkinson's disease without dementia, VH were associated with lower verbal immediate memory performance (Hedges' g -0.52). Both results survived correction for multiple comparisons. Abnormalities in these brain regions might reflect dysfunctions in brain networks sustaining visuoperceptive, attention, and executive abilities, with the latter also being at the basis of poor immediate memory performance.Recently the scientific community has seen a growing interest in the role of the gut-brain axis and, in particular, how probiotic supplementation may influence neural function and behaviour via manipulation of the gut microbiota. The purpose of this review was to systematically review the current literature exploring the effect of probiotic intervention on cognitive function. PsychINFO, Web of Science, PubMed and Google Scholar were searched for human trials. Studies selected for inclusion administered a probiotic intervention and included at least one behavioural measure of cognitive performance. A total of 30 experimental papers were included, exploring the effect of probiotics across a variety of ages, populations and cognitive domains. The evidence suggests there may be potential for probiotics to enhance cognitive function or attenuate cognitive decline, particularly in clinically relevant adult populations for whom cognitive dysfunction may be present. However, the limited number of studies and the quality of the existing research makes it challenging to interpret the data. Further research is clearly warranted. PROSPERO CRD42020164820.A complex assembly of lipids including fatty acids, cholesterol, and ceramides is vital to the integrity of the mammalian epidermal barrier. GSK-3 inhibitor The formation of this barrier requires oxidation of the substrate fatty acid, linoleic acid (LA), which is initiated by the enzyme 12R-lipoxygenase (LOX). In the epidermis, unoxidized LA is primarily found in long-chain acylceramides termed esterified omega-hydroxy sphingosine (EOS)/phytosphingosine/hydroxysphingosine (collectively EOx). The precise structure and localization of LOX-oxidized EOx in the human epidermis is unknown, as is their regulation in diseases such as psoriasis, one of the most common inflammatory diseases affecting the skin. Here, using precursor LC/MS/MS, we characterized multiple intermediates of EOx, including 9-HODE, 9,10-epoxy-13-HOME, and 9,10,13-TriHOME, in healthy human epidermis likely to be formed via the epidermal LOX pathways. The top layers of the skin contained more LA, 9-HODE, and 9,10,13-TriHOME EOSs, whereas 9,10-epoxy-13-HOME EOS was more prevalent deeper in the stratum corneum. In psoriatic lesions, levels of native EOx and free HODEs and HOMEs were significantly elevated, whereas oxidized species were generally reduced. A transcriptional network analysis of human psoriatic lesions identified significantly elevated expression of the entire biosynthetic/metabolic pathway for oxygenated ceramides, suggesting a regulatory function for EOx lipids in reconstituting epidermal integrity. The role of these new lipids in progression or resolution of psoriasis is currently unknown. We also discovered the central coordinated role of the zinc finger protein transcription factor, ZIC1, in driving the phenotype of this disease. In summary, long-chain oxygenated ceramide metabolism is dysregulated at the lipidomic level in psoriasis, likely driven by the transcriptional differences also observed, and we identified ZIC1 as a potential regulatory target for future therapeutic interventions.Surface epithelia provide a critical barrier to the outside world. Upon a barrier breach, resident epithelial and immune cells coordinate efforts to control infections and heal tissue damage. Inflammation can etch lasting marks within tissues, altering features such as scope and quality of future responses. By remembering inflammatory experiences, tissues are better equipped to quickly and robustly respond to barrier breaches. Alarmingly, in disease states, memory may fuel the inflammatory fire. Here, we review the cellular communication networks in barrier tissues and the integration between tissue-resident and recruited immune cells and tissue stem cells underlying tissue adaptation to environmental stress.