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Background: One of the core features of posttraumatic stress disorder (PTSD) is re-experiencing trauma. The anterior insula (AI) has been proposed to play a crucial role in these intrusive experiences. However, the dynamic function of the AI in re-experiencing trauma and its putative modulation by effective therapy need to be specified. Methods: Thirty PTSD patients were enrolled and exposed to traumatic memory reactivation therapy. Resting-state functional magnetic resonance imaging (fMRI) scans were acquired before and after treatment. To explore AI-directed influences over the rest of the brain, we referred to a mixed model using pre-/posttreatment Granger causality analysis seeded on the AI as a within-subject factor and treatment response as a between-subject factor. To further identify correlates of re-experiencing trauma, we investigated how intrusive severity affected (i) causality maps and (ii) the spatial stability of other intrinsic brain networks. Results: We observed changes in AI-directed functional connectivity patterns in PTSD patients. Many within- and between-network causal paths were found to be less influenced by the AI after effective therapy. Insular influences were found to be positively correlated with re-experiencing symptoms, while they were linked with a stronger default mode network (DMN) and more unstable central executive network (CEN) connectivity. Conclusion: We showed that directed changes in AI signaling to the DMN and CEN at rest may underlie the degree of re-experiencing symptoms in PTSD. A positive response to treatment further induced changes in network-to-network anticorrelated patterns. Such findings may guide targeted neuromodulation strategies in PTSD patients not suitably improved by conventional treatment.

Background The COVID-19 pandemic has raised concerns regarding its psychological effect on university students, especially healthcare students. We aimed at assessing the risk of mental health problems according to the type of university studies, by adjusting for potential confounders. Methods We used data from the COSAMe study, a national cross-sectional survey including 69,054 French university students during the first quarantine. The mental health outcomes evaluated were suicidal thoughts, severe self-reported distress (as assessed by the Impact of Events Scale–Revised), stress (Perceived Stress Scale), anxiety (State-Trait Anxiety Inventory, State subscale), and depression (Beck Depression Inventory). Multivariable logistic regression analyzes were performed to test the association between the type of university studies (healthcare studies: medical and non-medical, and non-healthcare studies) and poor mental health outcomes, adjusted for sociodemographic characteristics, precariousness indicators, health-related data, quality of social relationships, and data about media consumption. Results Compared to non-healthcare students (N = 59,404), non-medical healthcare (N = 5,431) and medical students (N = 4,193) showed a lower risk of presenting at least one poor mental health outcome (adjusted OR [95%CI] = 0.86[0.81–0.92] and 0.87[0.81–0.93], respectively). Compared to non-healthcare students, medical students were at lower risk of suicidal thoughts (0.83[0.74–0.93]), severe self-reported distress (0.75[0.69–0.82]) and depression (0.83[0.75–0.92]). Non-medical healthcare students were at lower risk of severe selfreported distress (0.79[0.73–0.85]), stress (0.92[0.85–0.98]), depression (0.83[0.76–0.91]), and anxiety (0.86[0.80–0.92]). Limitations This is a large but not representative cross-sectional study, limited to the first confinement. Conclusions Being a healthcare student is a protective factor for mental health problems among confined students. Mediating factors still need to be explored.

Envenoming due to Loxosceles spider bites still remains a neglected disease of particular medical concern in the Americas. To date, there is no consensus for the treatment of envenomed patients, yet horse polyclonal antivenoms are usually infused to patients with identified severe medical conditions. It is widely known that venom proteins in the 30–35 kDa range with sphingomyelinase D (SMasesD) activity, reproduce most of the toxic effects observed in loxoscelism. Hence, we believe that monoclonal antibody fragments targeting such toxins might pose an alternative safe and effective treatment. In the present study, starting from the monoclonal antibody LimAb7, previously shown to target SMasesD from the venom of L. intermedia and neutralize its dermonecrotic activity, we designed humanized antibody V-domains, then produced and purified as recombinant single-chain antibody fragments (scFvs). These molecules were characterized in terms of humanness, structural stability, antigen-binding activity, and venom-neutralizing potential. Throughout this process, we identified some blocking points that can impact the Abs antigen-binding activity and neutralizing capacity. In silico analysis of the antigen/antibody amino acid interactions also contributed to a better understanding of the antibody’s neutralization mechanism and led to reformatting the humanized antibody fragment which, ultimately, recovered the functional characteristics for efficient in vitro venom neutralization.

NMR spectroscopy was used to explore the different aspects of the normal and pathological functions of tau, but proved challenging because the protein contains 441 amino acids and has poor signal dispersion. We have set out to dissect the phosphorylation patterns of tau in order to understand better its role in the aggregation process and microtubule-binding regulation. Our current knowledge on the functional consequences of specific phosphorylations is still limited, mainly because producing and assessing quantitatively phosphorylated tau samples is far from straightforward, even in vitro. We use NMR spectroscopy as a proteomics tool to characterize the phosphorylation patterns of tau, after in vitro phosphorylation by recombinant kinases. The phosphorylated tau can next be use for functional assays or interaction assays with phospho-dependent protein partners, such as the prolyl cis–trans isomerase Pin1. [ABSTRACT FROM AUTHOR]