Flexible high-density microelectrode arrays for closed-loop brain-machine interfaces: a review.

Flexible high-density microelectrode arrays (HDMEAs) are emerging as a key component in closed-loop brain-machine interfaces (BMIs), providing high-resolution functionality for recording, stimulation, or both. The flexibility of these arrays provides advantages over rigid ones, such as reduced mismatch between interface and tissue, resilience to micromotion, and sustained long-term performance. This review summarizes the recent developments and applications of flexible HDMEAs in closed-loop BMI systems. It delves into the various challenges encountered in the development of ideal flexible HDMEAs for closed-loop BMI systems and highlights the latest methodologies and breakthroughs to address these challenges. These insights could be instrumental in guiding the creation of future generations of flexible HDMEAs, specifically tailored for use in closed-loop BMIs. The review thoroughly explores both the current state and prospects of these advanced arrays, emphasizing their potential in enhancing BMI technology.

Using Bayesian methods to clarify the role of trauma-related cognitions on the course of posttraumatic stress in nonspecific trauma-focused therapy.

OBJECTIVE: There is strong empirical evidence that a reduction of trauma cognitions lessens PTSD symptoms, but there are discrepancies, including evidence that baseline negative posttrauma cognitions are associated with more, less, or are not associated with changes in PTSD symptoms. Discrepancies may be a function of power, sample size, analytic method, or measure. METHODS: The rate of PTSD symptoms change across 16 trauma-focused treatment sessions in a community clinic (n = 56) was estimated using a Bayesian mixed-effects model with repeated measures nested within participants. Number of treatment sessions was the level-1 predictor variable with baseline levels of trauma-related cognitions (overaccommodation, assimilation, accommodation, and optimism) as time-invariant level-2 predictors. The relations between baseline trauma-related cognitions and PTSD symptoms change across sessions were assessed by cross-level interactions. RESULTS: PTSD symptoms declined over treatment (b = -1.57, 95% CrI [-1.89, -1.25]). Higher levels of overaccommodation and assimilation were associated with attenuated (b = .38, 95% CrI [.03, .73]) and greater (b = -.36, 95% CrI [-.69, -.02]) rates of symptom reduction, respectively. The relations between PTSD symptom reduction and accommodation (b = -.12, 95% CrI [-.43, .20]) and optimism (b = -.13, 95% CrI [-.45, .20]) were uncertain. CONCLUSIONS: There may be a nuanced role of trauma-related cognitions on PTSD symptoms during treatment. More research is needed to examine theoretically grounded trauma-related cognitions that align with the different treatments for PTSD, particularly in reference to the current diagnostic criteria for PTSD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cystatin C regulates the cytotoxicity of infection-induced endothelial-derived ß-amyloid.

Infection of rat pulmonary microvascular endothelial cells with the bacterium Pseudomonas aeruginosa induces the production and release of cytotoxic oligomeric tau and beta amyloid (Aß). Here, we characterized these cytotoxic amyloids. Cytotoxic behavior and oligomeric tau were partially resistant to digestion with proteinase K, but cytotoxicity was abolished by various denaturants including phenol, diethylpyrocarbonate (DEPC), and 1,1,1,3,3,3-hexafluoro-2-isopropanol (HFIP). Ultracentrifugation for 8 h at 150 000 g was required to remove cytotoxic activity from the supernatant. Ultracentrifugation, DEPC treatment, and immunodepletion using antibodies against Aß also demonstrated that cytoprotective protein(s) are released from endothelial cells during P. aeruginosa infection. Mass spectrometry of endothelial cell culture media following P. aeruginosa infection allowed identification of multiple potential secreted modulators of Aß, including cystatin C, gelsolin, and ApoJ/clusterin. Immunodepletion, co-immunoprecipitation, and ultracentrifugation determined that the cytoprotective factor released during infection of endothelial cells by P. aeruginosa is cystatin C, which appears to be in a complex with Aß. Cytoprotective cystatin C may provide a novel therapeutic avenue for protection against the long-term consequences of infection with P. aeruginosa.

The Pseudomonas aeruginosa exoenzyme Y impairs endothelial cell proliferation and vascular repair following lung injury.

Exoenzyme Y (ExoY) is a Pseudomonas aeruginosa toxin that is introduced into host cells through the type 3 secretion system (T3SS). Once inside the host cell cytoplasm, ExoY generates cyclic nucleotides that cause tau phosphorylation and microtubule breakdown. Microtubule breakdown causes interendothelial cell gap formation and tissue edema. Although ExoY transiently induces interendothelial cell gap formation, it remains unclear whether ExoY prevents repair of the endothelial cell barrier. Here, we test the hypothesis that ExoY intoxication impairs recovery of the endothelial cell barrier following gap formation, decreasing migration, proliferation, and lung repair. Pulmonary microvascular endothelial cells (PMVECs) were infected with P. aeruginosa strains for 6 h, including one possessing an active ExoY (PA103 exoUexoT::Tc pUCPexoY; ExoY(+)), one with an inactive ExoY (PA103ΔexoUexoT::Tc pUCPexoY(K81M); ExoY(K81M)), and one that lacks PcrV required for a functional T3SS (ΔPcrV). ExoY(+) induced interendothelial cell gaps, whereas ExoY(K81M) and ΔPcrV did not promote gap formation. Following gap formation, bacteria were removed and endothelial cell repair was examined. PMVECs were unable to repair gaps even 3-5 days after infection. Serum-stimulated growth was greatly diminished following ExoY intoxication. Intratracheal inoculation of ExoY(+) and ExoY(K81M) caused severe pneumonia and acute lung injury. However, whereas the pulmonary endothelial cell barrier was functionally improved 1 wk following ExoY(K81M) infection, pulmonary endothelium was unable to restrict the hyperpermeability response to elevated hydrostatic pressure following ExoY(+) infection. In conclusion, ExoY is an edema factor that chronically impairs endothelial cell barrier integrity following lung injury.