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Maternal immune activation (mIA) during pregnancy is hypothesised to disrupt offspring neurodevelopment and predispose offspring to neurodevelopmental disorders such as schizophrenia. Rodent models of mIA have explored possible mechanisms underlying this paradigm and provide a vital tool for preclinical research. However, a comprehensive analysis of the molecular changes that occur in mIA-models is lacking, hindering identification of robust clinical targets. This systematic review assesses mIA-driven transcriptomic and epigenomic alterations in specific offspring brain regions. Across 118 studies, we focus on 88 candidate genes and show replicated changes in expression in critical functional areas, including elevated inflammatory markers, and reduced myelin and GABAergic signalling proteins. Further, disturbed epigenetic markers at nine of these genes support mIA-driven epigenetic modulation of transcription. Overall, our results demonstrate that current outcome measures have direct relevance for the hypothesised pathology of schizophrenia and emphasise the importance of mIA-models in contributing to the understanding of biological pathways impacted by mIA and the discovery of new drug targets.Recurring episodes of excessive food intake in binge eating disorder can be understood through the lens of behavioral control systems patients repeat maladaptive behaviors against their explicit intent. Self-report measures show enhanced impulsivity and compulsivity in binge eating (BE) but are agnostic as to the processes that might lead to impulsive and compulsive behavior in the moment. Task-based neurocognitive investigations can tap into those processes. In this systematic review, we synthesize neurocognitive research on behavioral impulsivity and compulsivity in BE in humans and animals, published between 2010-2020. Findings on impulsivity are heterogeneous. Findings on compulsivity are sparse but comparatively consistent, indicating an imbalance of goal-directed and habitual control as well as deficits in reversal learning. We urge researchers to address heterogeneity related to mood states and the temporal dynamics of symptoms, to systematically differentiate contributions of body weight and BE, and to ascertain the validity and reliability of tasks. Moreover, we propose to further scrutinize the compulsivity findings to unravel the computational mechanisms of a potential reinforcement learning deficit.A critical unknown in the field of skeletal metastases is how cancer cells find a way to thrive under harsh conditions, as exemplified by metastatic colonization of adipocyte-rich bone marrow by prostate carcinoma cells. To begin understanding molecular processes that enable tumor cells to survive and progress in difficult microenvironments such as bone, we performed unbiased examination of the transcriptome of two different prostate cancer cell lines in the absence or presence of bone marrow adipocytes. Our RNAseq analyses and subsequent quantitative PCR and protein-based assays reveal that upregulation of endoplasmic reticulum (ER) stress and unfolded protein response (UPR) genes is a shared signature between metastatic prostate carcinoma cell lines of different origin. Pathway analyses and pharmacological examinations highlight the ER chaperone BIP as an upstream coordinator of this transcriptomic signature. see more Additional patient-based data support our overall conclusion that ER stress and UPR induction are shared, important factors in the response and adaptation of metastatic tumor cells to their micro-environment. Our studies pave the way for additional mechanistic investigations and offer new clues towards effective therapeutic interventions in metastatic disease.The autonomic nervous system (ANS) has received much attention as a potential low-cost, peripheral indicator of depression. Despite theoretical support, however, results have been mixed as to whether indices of the ANS reliably index depression. In response, the present study sought to clarify the relation between ANS activity and depression by examining cardiac autonomic balance (CAB) and cardiac autonomic regulation (CAR), two composite indices of the parasympathetic and sympathetic nervous system, within both a stressful and rewarding context. We hypothesized that CABStress, representing the difference between the parasympathetic and sympathetic branches in response to stress, and CARReward, representing the summation of the two branches in response to reward, will be most indicative of depressogenic risk. We examined the parasympathetic (i.e., respiratory sinus arrhythmia) and sympathetic (i.e., pre-ejection period) responses of 97 emerging adults (Mage = 18.93) for a stress (i.e., negative mood induction) and reward (i.e., probabilistic learning) task, as well as their depressive symptoms at baseline, 3-week, and 6-week follow-up. Analyses found partial support for our hypotheses, revealing greater CARReward (i.e., coactivation of both branches) was related to lower depressive symptoms. Further, exploratory analyses examining gender differences found lower CABStress (i.e., sympathetically-oriented response) was predictive of an increasing trajectory of depression, but only among males. Overall, the current study highlights the importance of simultaneously examining both branches of the ANS across various environmental contexts. Research and clinical implications of the current findings are discussed.

Common risk factors for gastrointestinal bleeding (GIB) are advanced age and the use of antiplatelet or anticoagulants drugs for the prevention of cardiovascular diseases.

In this prospective real-world observational study, oral anticoagulated patients were recruited and followed between June 2013 and December 2019. The primary end-point was to evaluate a possible relationship between bleeding events and patients’ clinical history of gastrointestinal disease prior to the start of the therapy. The secondary end-points were time of GIB appearance and the percentage of idiopathic or provoked events, i.e., bleeding due to a gastrointestinal disease. In case of GIB event all the patients were studied by means of endoscopic procedures. Cox regression was used to calculate the relative hazard ratios (HRs) of GIB for each considered clinical variable.

734 patients on both VKAs or DOACs were studied. Overall, 46 hemorrhagic events were recorded 6 were major bleeding (0.42/100 patient-years) while 43 were clinically relevant non major bleeding (2.