Associations of Vascular Risk with Cognition, Brain Glucose Metabolism, and Clinical Progression in Cognitively Intact Elders.

BACKGROUND: Increasing evidence supports an important role of vascular risk in cognitive decline and dementia. OBJECTIVE: This study aimed to examine whether vascular risk was associated with cognitive decline, cerebral hypometabolism, and clinical progression in cognitively intact elders. METHODS: Vascular risk was assessed by the Framingham Heart Study general Cardiovascular disease (FHS-CVD) risk score. The cross-sectional and longitudinal associations of FHS-CVD risk score with cognition and brain glucose metabolism were explored using multivariate linear regression and linear mixed effects models, respectively. The risk of clinical progression conversion was assessed using Kaplan-Meier survival curves and multivariate Cox proportional hazard models. RESULTS: A total of 491 cognitively intact elders were included from Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants with high FHS-CVD risk scores had lower baseline Mini-Mental State Examination (MMSE) (p = 0.009), executive function (EF) (p < 0.001), memory function (MEM) (p < 0.001) scores, and F18-fluorodeoxyglucose positron emission tomography (FDG-PET) uptake (p < 0.001) than those with low FHS-CVD risk scores. In longitudinal analyses, individuals with higher FHS-CVD risk scores had greater longitudinal declines in MMSE (p = 0.043), EF (p = 0.029) scores, and FDG-PET uptake (p = 0.035). Besides, individuals with a higher vascular risk had an increased risk of clinical progression (p = 0.004). CONCLUSION: These findings indicated effects of vascular risk on cognitive decline, cerebral hypometabolism, and clinical progression. Early detection and management of vascular risk factors might be useful in the prevention of dementia.

Efficient and Saturated Red Light-Emitting Electrochemical Cells Based on Cationic Iridium(III) Complexes with EQE up to 9.4 .

Solid-state light-emitting electrochemical cells (LECs) have several advantages, such as low-voltage operation, compatibility with inert metal electrodes, large-area flexible substrates, and simple solution-processable device architectures. However, most of the studies on saturated red LECs show low or moderate device efficiencies (external quantum efficiency (EQE) <3.3 %). In this work, we demonstrate a series of five red-emitting cationic iridium complexes (RED1--RED5) with 2,2'-biquinoline ligands and test their electroluminescence (EL) characteristics in LECs. The Commission Internationale de l'Eclairage (CIE) 1931 coordinates for the LECs based on these complexes are all beyond the National Television System Committee (NTSC) red standard point (0.67, 0.33). The maximal EQE of the neat-film RED1-based LECs reaches 7.4 %. The reddest complex, RED3, is doped in the blue-emitting host complex, BG, to fabricate host-guest LECs. The maximal EQE of the host-guest LECs (1 wt % complex RED3) reaches 9.4 %, which is among the highest reported for the saturated red LECs.

Traumatic brain injury in vivo and in vitro contributes to cerebral vascular dysfunction through impaired gap junction communication between vascular smooth muscle cells.

Gap junctions (GJs) contribute to cerebral vasodilation, vasoconstriction, and, perhaps, to vascular compensatory mechanisms, such as autoregulation. To explore the effects of traumatic brain injury (TBI) on vascular GJ communication, we assessed GJ coupling in A7r5 vascular smooth muscle (VSM) cells subjected to rapid stretch injury (RSI) in vitro and VSM in middle cerebral arteries (MCAs) harvested from rats subjected to fluid percussion TBI in vivo. Intercellular communication was evaluated by measuring fluorescence recovery after photobleaching (FRAP). In VSM cells in vitro, FRAP increased significantly (p<0.05 vs. sham RSI) after mild RSI, but decreased significantly (p<0.05 vs. sham RSI) after moderate or severe RSI. FRAP decreased significantly (p<0.05 vs. sham RSI) 30 min and 2 h, but increased significantly (p<0.05 vs. sham RSI) 24 h after RSI. In MCAs harvested from rats 30 min after moderate TBI in vivo, FRAP was reduced significantly (p<0.05), compared to MCAs from rats after sham TBI. In VSM cells in vitro, pretreatment with the peroxynitrite (ONOO(-)) scavenger, 5,10,15,20-tetrakis(4-sulfonatophenyl)prophyrinato iron[III], prevented RSI-induced reductions in FRAP. In isolated MCAs from rats treated with the ONOO(-) scavenger, penicillamine, GJ coupling was not impaired by fluid percussion TBI. In addition, penicillamine treatment improved vasodilatory responses to reduced intravascular pressure in MCAs harvested from rats subjected to moderate fluid percussion TBI. These results indicate that TBI reduced GJ coupling in VSM cells in vitro and in vivo through mechanisms related to generation of the potent oxidant, ONOO(-).

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation.

Surgical stress and anesthesia result in systemic immunosuppression. Propofol, a commonly used anesthetic agent, alters immune cell functions. Previously, we demonstrated that extracellular pressure increases macrophage phagocytosis. We hypothesized that propofol might influence pressure-induced macrophage phagocytosis in monocytes from patients undergoing surgery. Pressure (20 mmHg above ambient pressure) augmented phagocytosis in monocytes from non-propofol-anesthetized patients but reduced phagocytosis in monocytes from propofol-anesthetized patients. In vitro, propofol stimulated phagocytosis but reversed pressure-induced phagocytosis in THP-1 macrophages and monocytes from healthy volunteers. The GABA(A) receptor antagonists picrotoxin and SR-95531 did not affect basal THP-1 phagocytosis or prevent pressure-stimulated phagocytosis. However, picrotoxin and SR-95531 negated the inhibitory effect of pressure in propofol-treated cells without altering propofol-induced phagocytosis. Phosphorylation of the adaptor protein p130cas was inversely related to phagocytosis: it was inhibited by pressure or propofol but increased by pressure + propofol compared with propofol alone. Reduction of p130cas by small interfering RNA in THP-1 macrophages increased basal phagocytosis and prevented pressure and propofol effects. In conclusion, propofol may alter macrophage responses to pressure via the GABA(A) receptor and p130cas, whereas pressure also acts via p130cas but independently of GABA(A) receptors. p130cas may be an important target for modulation of macrophage function in anesthetized patients.