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Study of the initial steps of the CD95-mediated signaling pathways is a field of intense research and a long list of actors has been described in the literature. Nonetheless, the dynamism of protein-protein interactions (PPIs) occurring in the presence or absence of its natural ligand, CD95L, and the cellular distribution where these PPIs take place render it difficult to predict what will be the cellular outcome associated with the receptor engagement. Accordingly, CD95 stimulation can trigger apoptosis, necroptosis, pyroptosis, or pro-inflammatory signaling pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and phosphatidylinositol-3-kinase (PI3K). Recent data suggest that CD95 can also activate pattern recognition receptors (PRRs) known to sense damage-associated molecular patterns (DAMPs) such as DNA debris and dead cells. This activation might contribute to the pro-inflammatory role of CD95 and favor cancer development or severity of chronic inflammatory and auto-immune disorders. Herein, we discuss some of the molecular links that might connect the CD95 signaling to DAMP sensors.

Since the end of 2019, the world has been challenged by the coronavirus disease 2019 (COVID-19) pandemic. With COVID-19 cases rising globally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to evolve, resulting in the emergence of variants of interest (VOI) and of concern (VOC). Of the hundreds of millions infected, immunodeficient patients are one of the vulnerable cohorts that are most susceptible to this virus. These individuals include those with preexisting health conditions and/or those undergoing immunosuppressive treatment (secondary immunodeficiency). In these cases, several researchers have reported chronic infections in the presence of anti-COVID-19 treatments that may potentially lead to the evolution of the virus within the host. Such variations occurred in a variety of viral proteins, including key structural ones involved in pathogenesis such as spike proteins. Tracking and comparing such mutations with those arisen in the general population may provide information about functional sites within the SARS-CoV-2 genome. In this study, we reviewed the current literature regarding the specific features of SARS-CoV-2 evolution in immunocompromised patients and identified recurrent de novo amino acid changes in virus isolates of these patients that can potentially play an important role in SARS-CoV-2 pathogenesis and evolution.

Objectives: Two of Europe's most influential psychopathologists at the start of the twentieth century (Eugen Bleuler and Karl Jaspers) pointed out the fact that patients rarely act according to their delusions. This study proposes an investigation of how this issue is addressed in psychopathological literature. Methods: This article offers a critical review of psychopathological literature which focuses on the influence of delusional ideation on behaviour. Results: Phenomenological psychiatry has relied on the paradox pointed out by Bleuler and Jaspers to emphasize disorders of self-experience in psychosis whereas analytical philosophy of delusion has focused on the psychological status of delusion, regarded as belief, certainty, or imagination. The empirical studies conducted during the past three decades – which were devoted to acting on delusion – focused on violent and safety-seeking behaviours. These studies have shown that these behavioural disorders are motivated by an emotional outburst (anger and/or fear) rather than by delusional content. Conclusion: Delusional inconsequentiality can be clarified by conceptual research in phenomenological psychiatry and analytical philosophy, even though its role in the psychopathological processes has not yet been clearly identified or conceptualised. Empirical psychopathology on acting on delusion confirms the delusional inconsequentiality, but only implicitly, by highlighting the role of affectivity (rather than beliefs) in delusional actions. Given the major implications of better understanding this phenomenon, in terms of psychopathology and clinical practices, we suggest considering delusional inconsequentiality as a promising concept which could guide further research in contemporary psychopathology.

Macrophages are important effectors of tissue homeostasis, inflammation and host defense. They are equipped with an arsenal of pattern recognition receptors (PRRs) necessary to sense microbial- or danger-associated molecular patterns (MAMPs/DAMPs) and elicit rapid energetically costly innate immunity responses to protect the organism. The interaction between cellular metabolism and macrophage innate immunity is however not limited to answering the cell’s energy demands. Mounting evidence now indicate that in response to bacterial sensing, macrophages undergo metabolic adaptations that contribute to the induction of innate immunity signaling and/or macrophage polarization. In particular, intermediates of the glycolysis pathway, the Tricarboxylic Acid (TCA) cycle, mitochondrial respiration, amino acid and lipid metabolism directly interact with and modulate macrophage effectors at the epigenetic, transcriptional and post-translational levels. Interestingly, some intracellular bacterial pathogens usurp macrophage metabolic pathways to attenuate anti-bacterial defenses. In this review, we highlight recent evidence describing such host-bacterial immunometabolic interactions.