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  • bic Book Industry Communication::M Medicine  (4)
  • Frontiers Media SA  (4)
  • Berlin ; Heidelberg : Springer
  • English  (4)
  • 1
    Publication Date: 2023-12-21
    Description: There is abundant evidence showing a strong association between trauma exposure, psychotic symptoms, and posttraumatic stress disorder (PTSD). Early trauma exposure contributes to the formation of psychotic symptoms and the development of psychotic disorders or severe mental illnesses such as schizophrenia, bipolar disorder, and treatment-refractory major depression. Furthermore, among persons with psychotic disorders, multiple traumatization over the lifetime is common, due to factors such as social stigma, the criminalization of severe mental illness, and increased vulnerability to interpersonal victimization. In addition to these factors is the traumatic nature of experiencing psychotic symptoms and coercive treatments such as involuntary hospitalization and being placed in seclusion or restraints. Not surprisingly, these high rates of trauma lead to high rates of PTSD in people with psychotic disorders, which are associated with more severe symptoms, worse functioning, and greater use of acute care services. In addition to the impact of trauma on the development of psychotic disorders and comorbid PTSD, traumatic experiences such as childhood sexual and physical abuse can shape the nature of prominent psychotic symptoms such as the content of auditory hallucinations and delusional beliefs. Additionally, traumatic experiences have been implicated in the role of ‘stress responsivity’ and increased risk for transition to psychosis in those identified as being at clinical high risk of developing psychosis. Finally, although the diagnostic criteria for PTSD primarily emphasize the effects of trauma on anxiety, avoidance, physiological over-arousal, and negative thoughts, it is well established that PTSD is frequently accompanied by psychotic symptoms such as hallucinations and delusions that cannot be attributed to another DSM-V Axis I disorder such as psychotic depression or schizophrenia. Understanding the contribution of traumatic experiences to the etiology of psychosis and other symptoms can inform the provision of cognitive behavioral therapy for psychosis, including the development of a shared formulation of the events leading up to the onset of the disorder, as well as other trauma-informed treatments that address distressing and disabling symptoms associated with trauma and psychosis. Until recently the trauma treatment needs of this population have been neglected, despite the high rates of trauma and PTSD in persons with psychotic disorders, and in spite of substantial gains made in the treatment of PTSD in the general population. Fortunately, progress in recent years has provided encouraging evidence that PTSD can be effectively treated in people with psychotic disorders using interventions adapted from PTSD treatments developed for the general population. In contrast to clinician fears about the untoward effects of trauma-focused treatments on persons with a psychotic disorder, research indicates that post-traumatic disorders can be safely treated, and that participants frequently experience symptom relief and improved functioning. There is a need to develop a better understanding of the interface between trauma, psychosis, and post-traumatic disorder. This Frontiers Research Topic is devoted to research addressing this interface.
    Keywords: R5-920 ; RC435-571 ; BF1-990 ; Q1-390 ; Psychosis ; PTSD ; Auditory Hallucinations ; Negative Symptoms ; Childhood Trauma ; Trauma ; Psychological Interventions ; Lived Experience ; bic Book Industry Communication::M Medicine
    Language: English
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  • 2
    Publication Date: 2023-12-21
    Description: Neuropsychiatric disorders, covering both psychotic and depressive disorders, but also autism and attention-deficit hyperactivity disorder (ADHD), are characterized by abnormal behavior and brain structure. Accumulating evidence suggests that altered neurochemistry plays a role in these disorders and may have a causal relationship with the observed behavioral and structural abnormalities. To improve the understanding of neurochemical anomalies and (patho)physiological changes in psychiatric conditions, in vivo assessment of the affected tissue, the brain, is wanted and needed. Magnetic resonance spectroscopy (MRS) is a non-invasive technique which allows in vivo assessment of the molecular composition of brain tissues and identification of metabolites involved in physiological and pathological processes, which is otherwise virtually impossible. Only in the last decade with the development of high field MR methodologies, MRS has become sensitive enough for broader use in clinical studies. The implications are many, but proper guidance and elucidation of the pros and cons for the specific methods is needed to optimally exploit the potential. This Research Topic updates the reader on the possibilities and pitfalls of MRS today and highlights methodologies and applications for the future.
    Keywords: R5-920 ; RC435-571 ; Neurochemistry ; Neuroimaging ; Schizophrenia ; GABA ; 7 Tesla MRI ; Glutamate ; Functional MRS ; Psychiatry ; MR spectroscopy ; bic Book Industry Communication::M Medicine
    Language: English
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  • 3
    Publication Date: 2023-12-21
    Description: In his 1962 book "The Structure of Scientific Revolutions", Thomas Kuhn famously argued that researchers in every field of scientific enquiry always operate under a set of presuppositions known as paradigms that are rarely explicitly stated. In the field of HIV vaccine research, several prevailing paradigms led scientists for many years to pursue unfruitful lines of investigations that impeded significant progress. The uncritical acceptance of reigning paradigms makes scientists reluctant to abandon their mistaken assumptions even when they obtain results that are not consistent with the paradigms. The following five paradigms which disregard the degeneracy of the immune system were particularly harmful. 1) There is a primary and intrinsic epitope specific for each B cell receptor and for the corresponding monoclonal antibody. In reality, there is no single, intrinsic or "real" epitope for any antibody but only a diverse group of potential ligands. 2) Reactions with monoclonal antibodies are more specific than the combined reactivity of polyclonal antibodies. In reality, a polyclonal antiserum has greater specificity for a multiepitopic protein because different antibodies in the antiserum recognize separate epitopes on the same protein, giving rise to an additive specificity effect. By focusing vaccine design on single epitope-Mab pairs, the beneficial neutralizing synergy that occurs with polyclonal antibody responses is overlooked. 3) The HIV epitope identified by solving the crystallographic structure of a broadly neutralizing Mab – HIV Env complex should be able, when used as immunogen, to elicit antibodies endowed with the same neutralizing capacity as the Mab. Since every anti HIV bnMab is polyspecific, the single epitope identified in the complex is not necessarily the one that elicited the bnMab. Since hypermutated Mabs used in crystallographic studies differ from their germline-like receptor version present before somatic hypermutation, the identified epitope will not be an effective vaccine immunogen. 4) Effective vaccine immunogenicity can be predicted from the antigenic binding capacity of viral epitopes. Most fragments of a viral antigen can induce antibodies that react with the immunogen, but this is irrelevant for vaccination since these antibodies rarely recognize the cognate, intact antigen and even more rarely neutralize the infectivity of the viral pathogen that harbors the antigen. 5) The rational design of vaccine immunogens using reverse vaccinology is superior to the trial-and-error screening of vaccine candidates able to induce protective immunity. One epitope can be designed to increase its structural complementarity to one particular bnMab, but such antigen design is only masquerading as immunogen design because it is assumed that antigenic reactivity necessarily entails the immunogenic capacity to elicit neutralizing antibodies. When HIV Env epitopes, engineered to react with a bnMab are used to select from human donors rare memory B cells secreting bnAbs, this represents antigen design and not immunogen design. The aim of this Research Topic is to replace previous misleading paradigms by novel ones that better fit our current understanding of immunological specificity and will help HIV vaccine development.
    Keywords: R5-920 ; RC581-607 ; HIV tolerogenic vaccine ; germline antibodies ; SIV vaccine ; Mucosal vaccine ; Therapeutic vaccine ; vaccine efficacy trials ; neutralizing antibodies ; structure-based reverse vaccinology ; antibody polyspecificity ; bacterial adjuvants ; bic Book Industry Communication::M Medicine
    Language: English
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  • 4
    Publication Date: 2023-12-21
    Description: For the faultless function of the immune system, tight regulation of immune cell activation, immuno-suppression and the strength and efficiency of the immune response is essential. Immune checkpoint (ICP) molecules can amplify or dampen signals that lead to the modulation of specific immune activities. Under physiological conditions, immune checkpoints are essential to prevent autoimmune manifestations and to preserve self-tolerance. They help modulate immune responses by either promoting or inhibiting T-cell activation. However, in the context of cancer, malignant cells can dysregulate the expression of immune checkpoint proteins on immune cells in order to suppress anti-tumor immune responses and to gain immune resistance. Moreover, tumor cells themselves can also express some checkpoints proteins, thereby enabling these cells to externally orchestrate immune regulatory mechanisms. Several recent studies have confirmed that the expression of immune checkpoints could be an important prognostic parameter for cancer development and for patient outcome. Therefore, cancer immunotherapy based on the modulation of immune checkpoint molecules alone, or in combination with conventional tumor therapy (chemo- or/and radiotherapy), is now in focus as a means of developing new therapeutic strategies for different types of cancer. The two well-known molecules – CTLA4 and PD-1 - serve as important examples of such checkpoint proteins of important therapeutic potential. Thus far, inhibitors of CTLA4 and PD-1 have been approved to treat only a limited number of malignancies (e.g. malignant Melanoma, Non-Small Cell Lung Cancer). Many others are currently under investigation and the list of immune checkpoint molecules for potential therapeutic targeting is still growing. However, the clinical response to inhibitors of checkpoint molecules is not sufficient in all cases. Therefore, further studies are needed to improve our knowledge of such immunomodulatory proteins and their associated signaling pathways. Several key signaling pathways which are involved in the regulation of expression of checkpoint molecules in immune cells and in cancer cells have already been identified including MAPK, PI3K, NF-kB, JAKs and STATs. These (and future discovered) signaling pathways could give rise to the development of new strategies for modulating the expression of ICPs and thereby, improving anti-cancer immune responses. The main aim of the Research Topic is to collect novel findings from scientists involved in basic research on immune checkpoints as well as in translational studies investigating the use of checkpoint inhibtors in immunotherapy in experimental settings. We welcome the submission of Review, Mini-Review and Original Research articles that cover the following topics: 1. Molecular mechanisms underlying regulation of ICP expression in immune and/or cancer cells. 2. Characterization of signaling pathways downstream ICP molecules. 3. Cellular responses to ICP blockade. 4. Identification of new compounds interfering with ICP expression and/or signaling. 5. ICP-mediated interactions between cancer cells and immune cells. 6. Functional links between ICP and cytokines/chemokines. 7. Molecular mechanisms of ICP inhibition in the context of experimental cancer immunotherapy.
    Keywords: R5-920 ; RC581-607 ; RC254-282 ; CTLA-4 (CD152) ; checkpoint blockade ; Immunosuppression ; cancer immunotherapy ; PD-1 (CD279) ; Tumor Microenvironment ; Metabolic checkpoints ; immune checkpoint molecules ; cytotoxic T lymphocytes ; PDL1 ; bic Book Industry Communication::M Medicine
    Language: English
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