Sports-related injury is frequently associated with repeated diffuse and mild traumatic brain injury (mTBI). We combined two existing models for inducing TBI in rats, the Impact Acceleration and Controlled Cortical Impact models, to create a new method relevant to the study of cognitive sequelae of repeat mTBI in adolescent athletes. Repeated mTBI, such as those incurred in sports, can result in a wide range of outcomes, with many individuals experiencing no chronic sequela while others develop profound cognitive and behavioral impairments, typically in the absence of lasting motor symptoms or gross tissue loss appreciable antemortem. It is critical to develop models of mTBI and repeat mTBI that have the flexibility to assess multiple parameters related to injury (e.g. number and magnitude of impacts, inter-injury interval, etc) that are associated with brain vulnerability compared to normal recovery. We designed a 3D-printed plastic implant to permanently secure a metal disc to the skull of adolescent rats ication of NeuN. Therefore, by implanting a helmet we have created a relevant model of sports-related injury and repeated mTBI that results in subtle but significant changes in cognitive outcome in the absence of significant hippocampal cell death.As immunotherapy agents are incorporated into the routine oncological practice, the number of patients at the risk of immune-related adverse events has increased dramatically. However, the prompt identification and effective management of severe autoimmune complications remain a challenge. We report the case of a patient with metastatic lung adenocarcinoma who experienced a fatal autoimmune storm 3 weeks after the first dose of anti-programmed death receptor-1 (PD-1) agent pembrolizumab, which included thyroiditis, hepatitis, myositis, myocarditis, pneumonitis, and myasthenia gravis. Aggressive autoimmunity was supported by extensive T-cell and macrophage tissue infiltrates and autoantibody positivity. Remarkably, no residual tumor was found at autopsy. This case illustrates the potential harm caused by immunotherapy and our limited knowledge on its prevention, treatment, and association to antitumor efficacy.The ligands that comprise the Transforming Growth Factor β superfamily highly govern the development of the embryonic growth plate. Members of this superfamily activate canonical TGFβ and/or BMP (Bone Morphogenetic Protein) signaling pathways. How these pathways interact with one another is an area of active investigation. These two signaling pathways have been described to negatively regulate one another through crosstalk involving Smad proteins, the primary intracellular effectors of canonical signaling. More recently, a mechanism for regulation of the BMP pathway through TGFβ and BMP receptor interactions has been described. Here in this review, we demonstrate examples of how TGFβ is a gatekeeper of BMP action in the developing growth plate at both the receptor and transcriptional levels.Psychoactive drugs with addiction potential are widely used by people of virtually all cultures in a non-addictive way. In order to understand this behaviour, its population penetrance, and its persistence, drug instrumentalization was suggested as a driving force for this consumption. buy Onametostat Drug instrumentalization theory holds that psychoactive drugs are consumed in a very systematic way in order to make other, non-drug-related behaviours more efficient. Here, we review the evolutionary origin of this behaviour and its psychological mechanisms and explore the neurobiological and neuropharmacological mechanisms underlying them. Instrumentalization goals are discussed, for which an environmentally selective and mental state-dependent consumption of psychoactive drugs can be learned and maintained in a non-addictive way. A small percentage of people who regularly instrumentalize psychoactive drugs make a transition to addiction, which often starts with qualitative and quantitative changes in the instrumentalization goals. As such, addiction is proposed to develop from previously established long-term drug instrumentalization. Thus, preventing and treating drug addiction in an individualized medicine approach may essentially require understanding and supporting personal instrumentalization goals.Inflammatory pain is commonly associated with cognitive impairment. However, its molecular mechanisms are poorly understood. Thus, this study was conducted to investigate the molecular mechanisms of behavioral changes associated with inflammatory pain. Briefly, 36 Wistar rats were randomly divided into two main groups CFA group treated with 100 μL of Complete Freunds’ Adjuvant (CFA) and CFA + Minocycline group treated with 100 μL of CFA+40 mg/kg/day of minocycline). After that, each group was divided into three subgroups based on different time points of the study. The pain was induced using CFA and subsequent behavioral changes (i.e., hyperalgesia and learning and spatial memory) were analyzed by the Morris Water Maze (MWM) task and Radiant Heat. Then, the cellular and molecular changes were assessed using Western Blotting, Immunohistochemistry, and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) techniques. Results of the study indicated that CFA-induced pain impaired spatial learning and memory functions. Studying the cellular changes showed that persistent inflammatory pain increased the microglial activity in CA1 and Dentate Gyrus (DG) regions. Furthermore, an increase was observed in the percentage of TUNEL-positive cells. Also, pro-Brain-Derived Neurotrophic Factor (BDNF)/BDNF ratio, Caspase3, and Receptor-Interacting Protein kinase 3 (RIP3) levels increased in the rats’ hippocampus following induction of persistent inflammatory pain. These changes were reversed following the cessation of pain as well as the injection of minocycline. Taking together, the results of the current study for the first time revealed that an increase in the microglia dependent proBDNF/BDNF ratio following persistent inflammatory pain leads to cell death of the CA1 and DG neurons that subsequently causes a cognitive deficit in the learning and spatial memory functions.