Emotion Regulation Processes and Psychoform and Somatoform Dissociation in Adolescents and Young Adults with Cumulative Maltreatment

The relationship between childhood trauma and dissociative experiences is widely acknowledged. However, the association between emotion regulation difficulties (ERD), anxiety/depression and dissociation in adolescents and young adults with cumulative maltreatment (CM) remains unclear. The present study examined the role of ERD at both intrapersonal and interpersonal levels and anxiety/depression symptoms in the development of psychoform or somatoform dissociation in adolescents and young adults with CM. We assessed 58 participants with CM and 55 participants without childhood trauma history between the age of 12 and 22 years old. Participants completed self-reports of ERD, anxiety/depression, psychoform dissociation and somatoform dissociation. The results revealed that adolescents and young adults exposed to CM displayed high levels of psychoform and somatoform dissociation, ERD and anxiety/depression symptoms. It was also found that intrapersonal and interpersonal ERD predicted psychoform dissociation, whereas anxiety/depression predicted somatoform dissociation in adolescents and young adults with CM. Intrapersonal and interpersonal ERD and anxiety/depression are therapy targets for clinical interventions in adolescents and young adults with CM and dissociative symptoms.     

Differential Diagnosis between Anomalous Experiences and Dissociation Disorder Using the Dissociative Disorders Interview Schedule (DDIS)

Background. It is important to understand the most diverse cultural aspects related to religiosity. Scientifically, it is important to understand religious manifestations and their relation to health, and to differentiate them from psychopathological manifestations. Objective. To evaluate the mental health of a group of mediums and compare it with that of a control group from the same religious context who do not manifest mediumship, using the Dissociative Disorders Interview Schedule (DDIS). Methods. This was a cross-sectional study, evaluating 47 mediums (Group 1) and comparing them with 22 non-medium volunteers from the same religious context (Group 2) using the DDIS questionnaire. All results were matched with historical data from patients with dissociative identity disorder (DID) who answered the DDIS. Results. Scores obtained from the DDIS were similar in both groups. The number of positive symptoms was comparable in a wide range of analyzed areas, involving but not being restricted to somatization disorder, major depressive episode, borderline personality disorder, extrasensory/paranormal experiences, physical/sexual abuse and five dissociative disorders. There were considerable differences when we compared these results with historical data from patients with DID. Conclusion. In agreement with the extant literature, these results showed that mediumship can be considered a non-pathological form of dissociative phenomena.     

Neuropilin-2 contributes to tumor progression in preclinical models of small intestinal neuroendocrine tumors

The identification of novel regulators of tumor progression is a key challenge to gain knowledge on the biology of small intestinal neuroendocrine tumors (SI-NETs). We recently identified the loss of the axon guidance protein semaphorin 3F as a protumoral event in SI-NETs. Interestingly the expression of its receptor neuropilin-2 (NRP-2) was still maintained. This study aimed at deciphering the potential role of NRP-2 as a contributor to SI-NET progression. The role of NRP-2 in SI-NET progression was addressed using an approach integrating human tissue and serum samples, cell lines and in vivo models. Data obtained from human SI-NET tissues showed that membranous NRP-2 expression is present in a majority of tumors, and is correlated with invasion, metastatic abilities, and neovascularization. In addition, NRP-2 soluble isoform was found elevated in serum samples from metastatic patients. In preclinical mouse models of NET progression, NRP-2 silencing led to a sustained antitumor effect, partly driven by the downregulation of VEGFR2. In contrast, its ectopic expression conferred a gain of aggressiveness, driven by the activation of various oncogenic signaling pathways. Lastly, NRP-2 inhibition led to a decrease of tumor cell viability, and sensitized to therapeutic agents. Overall, our results point out NRP-2 as a potential therapeutic target for SI-NETs, and will foster the development of innovative strategies targeting this receptor. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Cold atmospheric plasma modulates endothelial nitric oxide synthase signalling and enhances burn wound neovascularisation

Treatment with cold atmospheric plasma (CAP) has been reported to promote wound healing in animals. However, how this process is mediated remains unclear. In this study we examined the mechanisms which underlie the improved wound healing effects of CAP and the roles of associated reactive oxygen and nitrogen species (RONS), which are generated by plasma. By using in vitro models which mimicked various steps of angiogenesis, we demonstrated that CAP triggered the production of nitric oxide (NO), and enhanced cell migration and the assembly of endothelial cells into vessel-like structures. These are both hallmarks of the proliferative phase of wound healing. Using a mouse model of a third-degree burn wound, we went on to show that CAP treatment was associated with enhanced angiogenesis, characterised by accelerated in vivo wound healing and increased cellular proliferation. Here, CAP significantly increased the in vivo production of endothelial NO synthase (eNOS), an enzyme that catalyses NO synthesis in endothelial cells, and significantly increased the expression of pro-angiogenic PDGFRβ and CD31 markers in mouse wounds. Mechanistically, we showed that CAP induced eNOS phosphorylation and activation, thereby increasing the levels of endogenous NO in endothelial cells. Increased NO generation facilitated by CAP further stimulated important pro-angiogenic VEGFA/VEGFR2 signalling in vitro. This proof-of-concept study may guide future efforts aimed at addressing the use of physical plasma and its therapeutic applications in a variety of pathological scenarios. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

CD93 is a cell surface lectin receptor involved in the control of the inflammatory response stimulated by exogenous DNA

Bacterial DNA contains CpG oligonucleotide (ODN) motifs to trigger innate immune responses through the endosomal receptor Toll-like receptor 9 (TLR9). One of the cell surface receptors to capture and deliver microbial DNA to intracellular TLR9 is the C-type lectin molecule DEC-205 through its N-terminal C-type lectin-like domain (CTLD). CD93 is a cell surface protein and member of the lectin group XIV with a CTLD. We hypothesized that CD93 could interact with CpG motifs, and possibly serve as a novel receptor to deliver bacterial DNA to endosomal TLR9. Using ELISA and tryptophan fluorescence binding studies we observed that the soluble histidine-tagged CD93-CTLD was specifically binding to CpG ODN and bacterial DNA. Moreover, we found that CpG ODN could bind to CD93-expressing IMR32 neuroblastoma cells and induced more robust interleukin-6 secretion when compared with mock-transfected IMR32 control cells. Our data argue for a possible contribution of CD93 to control cell responsiveness to bacterial DNA in a manner reminiscent of DEC-205. We postulate that CD93 may act as a receptor at plasma membrane for DNA or CpG ODN and to grant delivery to endosomal TLR9.     

Immunoregulatory role of acid sphingomyelinase in allergic asthma

Acid sphingomyelinase (ASM) is one of the enzymes that catalyzes the breakdown of sphingomyelin to ceramide and phosphorylcholine. In this study, we aimed at elucidating the role of ASM in allergic asthma. We used an ovalbumin-induced murine model of asthma where we compared wild-type and ASM-deficient mice. In wild-type mice, secretory ASM activity in the bronchoalveolar lavage fluid was increased in the acute ovalbumin model, but not in a tolerogenic model. Furthermore, in the absence of ASM, the serum IgE level was reduced, compared with wild-type mice, while an accumulation of interstitial macrophages and foreign antigen-induced regulatory T cells along with exhausted CD4⁺ PD1⁺ T cells was observed in the lungs of ASM^−/− mice. In conclusion, in the absence of ASM, we observed an accumulation of immunosuppressive antigen-induced regulatory T cells expressing Foxp3 and CTLA4 in the lung as well as multinucleated interstitial macrophages and exhausted CD4⁺ PD1⁺ T cells associated with inhibition of serum IgE in asthma.