Coronavirus disease 2019 (COVID-19) can damage cerebral small vessels and cause neurological symptoms. Here we describe structural changes in cerebral small vessels of patients with COVID-19 and elucidate potential mechanisms underlying the vascular pathology. In brains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals and animal models, we found an increased number of empty basement membrane tubes, so-called string vessels representing remnants of lost capillaries. We obtained evidence that brain endothelial cells are infected and that the main protease of SARS-CoV-2 (Mpro) cleaves NEMO, the essential modulator of nuclear factor-κB. By ablating NEMO, Mpro induces the death of human brain endothelial cells and the occurrence of string vessels in mice. Deletion of receptor-interacting protein kinase (RIPK) 3, a mediator of regulated cell death, blocks the vessel rarefaction and disruption of the blood–brain barrier due to NEMO ablation. Importantly, a pharmacological inhibitor of RIPK signaling prevented the Mpro-induced microvascular pathology. Our data suggest RIPK as a potential therapeutic target to treat the neuropathology of COVID-19.
BackgroundWeb-based and blended (face-to-face plus Web-based) interventions for mental health disorders are gaining significance. However, many licensed psychotherapists still have guarded attitudes toward computer-assisted therapy, hindering dissemination efforts.ObjectiveThe objective of this study was to provide a therapist-oriented evaluation of Web-based and blended therapies and identify commonalities and differences in attitudes toward both formats. Furthermore, it aimed to test the impact of an information clip on expressed attitudes.MethodsIn total, 95 Austrian psychotherapists were contacted and surveyed via their listed occupational email address. An 8-minute information video was shown to half of the therapists before 19 advantages and 13 disadvantages had to be rated on a 6-point Likert scale.ResultsThe sample resembled all assessed properties of Austrian psychotherapists (age, theoretical orientation, and region). Therapists did not hold a uniform overall preference. Instead, perceived advantages of both interventions were rated as neutral (t94=1.89, P=.06; d=0.11), whereas Web-based interventions were associated with more disadvantages and risks (t94=9.86, P<.001; d=0.81). The information clip did not excerpt any detectable effect on therapists’ attitudes (r95=−.109, P=.30). The application of modern technologies in the own therapeutic practice and cognitive behavioral orientation were positively related to the given ratings.ConclusionsThis study is the first to directly compare therapists’ attitudes toward Web-based and blended therapies. Positive attitudes play a pivotal role in the dissemination of new technologies, but unexperienced therapists seem to lack knowledge on how to benefit from technology-aided treatments. To speed up implementation, these aspects need to be addressed in the development of new interventions. Furthermore, the preference of blended treatments over Web-based interventions seems to relate to avoidance of risks. Although this study is likely to represent therapists’ attitudes in countries with less advanced electronic health services, therapists’ attitudes in more advanced countries might present differently.
BackgroundBlended interventions aim to capitalise on the strengths of both computer-based and face-to-face therapy. Studies on this innovative treatment format remain scare. This especially accounts for the group treatment of depression.MethodThe present study applied eclectic psychotherapy methods to an adult sample exhibiting a variety of depressive symptoms (N = 46). Participants were recruited by a newspaper inlet and randomised either to a treatment or a waiting list condition. Computer supported components were multimedia group sessions, e-learning, online videos and worksheets, remote therapist-patient communication and online pre-post-assessment.ResultsLarge between-group effect sizes on primary outcome depressiveness (CES-D) (F(1,44) = 4.88, p = 0.032; d = 0.87) and secondary outcome personal resources (resource scales) (F(1,44) = 9.04, p = 0.004; d = 0.73 to F(1,44) = 8.82 p = 0.005, d = 1.15) were found in the intention to treat analysis (ANOVA). Subjective evaluation of the intervention revealed high treatment adherence (91%) and high perceived relevance of supportive computer and multimedia components. Participants rated computer and multimedia components comparable to treatment elements such as group interaction or specific cognitive behavioural exercises, and 25% associated the utilisation of those components with treatment success. Depressiveness and age did not predict the utilisation and the appraisal of computer and multimedia components.DiscussionResults provide preliminary support for the acceptability and feasibility of the investigated blended treatment in a group with non-specific depressive symptoms. However, small sample size and lack of diagnostics restrict generalizability. Additional research in clinical settings is needed.
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