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There is a paucity of empirical studies exploring wishes to die (WTD) in older adults without a life-threatening disease or psychiatric disorder, especially on how these WTD evolve over time.

This study aims to deepen our understanding of living with a WTD by elucidating multifaceted trajectories of death wishes in older adults without a life-threatening disease or psychiatric disorder.

Interviews were conducted between 2013 and 2019 with Dutch men and women aged 70 and older who expressed a WTD (preferably at a self-chosen moment). Using a phenomenological, longitudinal analysis approach, 35 serial interviews were analyzed.

This resulted in four thematic meanings following four trajectories, namely 1) a realized WTD, facing the ultimate decision with both freedom and a sense of fate; 2) an intensifying WTD, reaching a deadlock; 3) a diminishing WTD, experiencing tentative space for new possibilities; and 4) a vanishing WTD, being surprised by an unexpected turn. In the cases examined, the individualsd/or desire to act on their WTD. Often such changes were related to (re-)establishment of connections with other people and/or society or with themselves. Since most research in this area is cross-sectional, the current longitudinal findings of this study are unique in providing insight into changes over time, thus contributing to the fields of death and suicide studies.The hypothesis of chronically low brain serotonin levels as pathophysiologically linked to impulsive aggression has been around for several decades. Whereas the theory was initially based on indirect methods to probe serotonin function, our understanding of the neural mechanisms involved in impulsive aggression has progressed with recent advances in neuroimaging. The review integrates evidence based on data from several neuroimaging domains in humans. In vivo molecular neuroimaging findings demonstrate associations between impulsive aggression and high serotonin 1B and serotonin 4 receptor binding, high serotonin transporter levels, and low monoamine oxidase A levels, suggesting that low interstitial serotonin levels are a neurobiological risk factor for impulsive aggressive behavior. Imaging genetics suggests that serotonergic-related genetic polymorphisms associate with antisocial behavior, and some evidence indicates that the low-expressing monoamine oxidase A genotype specifically predisposes to impulsive aggression, which may be mediated by effects on corticolimbic function. Interventions that (presumably) alter serotonin levels have effects on brain activity within brain regions involved in impulsive aggression, notably the amygdala, dorsal striatum, anterior cingulate, insula, and prefrontal cortex. Based on these findings, we propose a model for the modulatory role of serotonin in impulsive aggression. Future studies should ensure that clinical features unique for impulsive aggression are appropriately assessed, and we propose investigations of knowledge gaps that can help confirm, refute, or modify our proposed model of impulsive aggression.Traumatic brain injury (TBI) is an established risk factor for the development of psychiatric disorders, especially depression and anxiety. However, the mechanistic pathways underlying this risk remain unclear, limiting treatment options and hindering the identification of clinically useful biomarkers. One salient pathophysiological process implicated in both primary psychiatric disorders and TBI is inflammation. An important consequence of inflammation is the increased breakdown of tryptophan to kynurenine and, subsequently, the metabolism of kynurenine into several neuroactive metabolites, including the neurotoxic NMDA receptor agonist quinolinic acid and the neuroprotective NMDA receptor antagonist kynurenic acid. Here, we review studies of the kynurenine pathway (KP) in TBI and examine their potential clinical implications. The weight of the literature suggests that there is increased production of neurotoxic kynurenines such as quinolinic acid in TBI of all severities and that elevated quinolinic acid concentrations in both the cerebrospinal fluid and blood are a negative prognostic indicator, being associated with death, magnetic resonance imaging abnormalities, increased depressive and anxiety symptoms, and prolonged recovery. We hypothesize that an imbalance in KP metabolism is also one molecular pathway through which the TBI-induced neurometabolic cascade may predispose to the development of psychiatric sequelae. If this model is correct, KP metabolites could serve to predict who is likely to develop psychiatric illness while drugs that target the KP could help to prevent or treat depression and anxiety arising in the context of TBI.Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) characterized by the development of microangiopathic haemolytic anaemia, thrombocytopenia, and ischaemic organ dysfunction associated with ADAMTS13 levels lower than 10% in most cases. Recently there have been numerous advances in the field of PTT, new, rapid and accessible techniques capable of quantifying ADAMTS13 activity and inhibitors. The massive sequencing systems facilitate the identification of polymorphisms in the ADAMTS13 gene. selleck chemical In addition, new drugs such as caplacizumab have appeared and relapse prevention strategies are being proposed with the use of rituximab. The existence of TTP patient registries allow a deeper understanding of this disease but the great variability in the diagnosis and treatment makes it necessary to elaborate guidelines that homogenize terminology and clinical practice. The recommendations set out in this document were prepared following the AGREE methodology. The research questions were formulated according to the PICO format. A search of the literature published during the last 10 years was carried out. The recommendations were established by consensus among the entire group, specifying the existing strengths and limitations according to the level of evidence obtained. In conclusion, this document contains recommendations on the management, diagnosis, and treatment of TTP with the ultimate objective of developing guidelines based on the evidence published to date that allow healthcare professionals to optimize TTP treatment.