Wave transmission and vibration response in periodically stiffened plates using a free wave approach.

There are various structures constructed with periodically stiffened thin plates. Vibration prediction of such structures is not easy compared to the structures comprised of uniform plates only due to the mathematical complexity stemmed from the periodic nature. This study provides the analytic method to predict the wave transmission at junctions connecting two semi-infinite periodic structures and the response of a finite periodic structure to an external harmonic point force. The same theoretical framework is employed for dealing with both phenomena. First, free wave solutions are obtained by solving the governing equation for the bending motion of a periodically stiffened, infinite plate using the spatial Fourier Transform and the Floquet's theorem. Then, the free wave solutions are linearly superposed, and the linear coefficients are calculated by applying the appropriate boundary conditions. Numerical simulation is conducted. In dealing with the periodic finite structure, the result is compared with that by the finite element analysis. It is revealed that the periodic nature of the structures affects both the energy transmission and the vibration response of the periodically stiffened plates.

Pseudomonas aeruginosa DnaK Stimulates the Production of Pentraxin 3 via TLR4-Dependent NF-κB and ERK Signaling Pathways.

Microbe-derived factors trigger innate immune responses through the production of inflammatory mediators, including pentraxin 3 (PTX3). PTX3 is a soluble pattern recognition molecule that stimulates the clearance of clinically important bacterial pathogens such as Pseudomonas aeruginosa. However, the P. aeruginosa factors responsible for the production of PTX3 have not been elucidated. In this study, we found that P. aeruginosa DnaK, a homolog of heat shock protein 70, induced PTX3 production. Induction was mediated by intracellular signals transmitted through the Toll-like receptor 4 (TLR4) signaling pathway. Following receptor engagement, the stimulatory signals were relayed initially through the nuclear factor kappa B (NF-κB) signaling pathway and subsequently by extracellular signal-regulated kinases (ERK), which are mitogen-activated protein kinases. However, ERK activation was negatively controlled by NF-κB, implying the existence of negative crosstalk between the NF-κB and the ERK pathways. These data suggest that P. aeruginosa DnaK acts as a pathogen-associated molecular pattern to trigger modulation of host defense responses via production of PTX3.

HSP70-Homolog DnaK of Pseudomonas aeruginosa Increases the Production of IL-27 through Expression of EBI3 via TLR4-Dependent NF-κB and TLR4-Independent Akt Signaling.

IL-27, a heterodimeric cytokine composed of the p28 subunit and Epstein-Barr virus-induced gene 3 (EBI3), acts as a potent immunosuppressant and thus limits pathogenic inflammatory responses. IL-27 is upregulated upon Pseudomonas aeruginosa infection in septic mice, increasing susceptibility to the infection and decreasing clearance of the pathogen. However, it remains unclear which P. aeruginosa-derived molecules promote production of IL-27. In this study, we explored the mechanism by which P. aeruginosa DnaK, a heat shock protein 70-like protein, induces EBI3 expression, thereby promoting production of IL-27. Upregulation of EBI3 expression did not lead to an increase in IL-35, which consists of the p35 subunit and EBI3. The IL-27 production in response to DnaK was biologically active, as reflected by stimulation of IL-10 production. DnaK-mediated expression of EBI3 was driven by two distinct signaling pathways, NF-κB and Akt. However, NF-κB is linked to TLR4-associated signaling pathways, whereas Akt is not. Taken together, our results reveal that P. aeruginosa DnaK potently upregulates EBI3 expression, which in turn drives production of the prominent anti-inflammatory cytokine IL-27, as a consequence of TLR4-dependent activation of NF-κB and TLR4-independent activation of the Akt signaling pathway.

Negative regulation of interleukin 1ß expression in response to DnaK from Pseudomonas aeruginosa via the PI3K/PDK1/FoxO1 pathways.

Interleukin (IL)-1ß is crucial for a wide range of inflammatory responses. Previously, we reported that IL-1ß is produced in response to Pseudomonas aeruginosa-derived DnaK via NF-κB and JNK pathways; however, the signaling pathways that counter the process to maintain IL-1ß homeostasis are unknown. Here, we show that DnaK-mediated expression of IL1ß is increased markedly in macrophages upon blockade of PI3K/PDK1. This was verified by measuring released IL-1ß protein. The negative effect of PI3K on IL-1ß production was dependent on suppression of both NF-κB and JNK activation. Intriguingly, PDK1 (an underlying mediator of PI3K) acted as an upstream regulator for the activation of NF-κB, but downregulated JNK activation. Furthermore, production of IL-1ß and activation of JNK were triggered by inhibition of phosphorylated FoxO1; phosphorylation of FoxO1 was controlled by PDK1 signaling in response to DnaK. Thus, IL-1ß production is modulated by P. aeruginosa-derived DnaK via cross-talk between JNK and PI3K/PDK1/FoxO1 pathways.

The Pseudomonas aeruginosa HSP70-like protein DnaK induces IL-1ß expression via TLR4-dependent activation of the NF-κB and JNK signaling pathways.

IL-1ß expression is increased in response to P. aeruginosa infection, but the responsible proteins have not been clearly elucidated. Here, we demonstrate for the first time that IL-1ß expression is induced in response to the heat shock protein 70-like protein DnaK. Treatment with recombinant DnaK (rDnaK) increased IL-1ß expression in a dose- and time-dependent manner, and the release of mature IL-1ß in response to rDnaK was detected to an extent similar to that stimulated by the well-known agonists, lipopolysaccharide and nigericin. rDnaK-mediated IL-1ß expression was driven by the NF-κB signaling pathway. In addition, expression was controlled by the JNK signaling pathway, although these two signaling cascades act independently upon rDnaK stimulation. Finally, rDnaK-induced IL-1ß expression was initiated via the action of TLR4. Taken together, the data reveal that P. aeruginosa-derived DnaK induces expression of IL-1ß via TLR4-dependent activation of the NF-κB and JNK signaling pathways.

T3SS effector ExoY reduces inflammasome-related responses by suppressing bacterial motility and delaying activation of NF-κB and caspase-1.

Type III-secreted effectors are essential for modulating host immune responses during the pathogenesis of Pseudomonas aeruginosa infections. Little is known about the impact of one of the effectors, ExoY, on inflammasome activation, which results in IL-1ß production and pyroptotic cell death. In this study, we found that transcriptional expression of Il-1ß was induced to a lesser extent in response to an exoY-harboring strain than to a deleted mutant. This suppressive effect of ExoY was verified by complementation assay as well as by direct translocation of exoY into host cells. In addition to the production of IL-1ß, pyroptotic cell death was also diminished in response to an exoY-harboring strain. These inflammasome responses were mediated by the adenylate cyclase activity of ExoY, which plays a role in delaying the activation of NF-κB and caspase-1, a key component of inflammasome-mediated responses. Moreover, the negative effects of ExoY on these responses were in part conferred by the suppression of bacterial motility, which could reduce the degree of bacterial contact with cells. Together, these results demonstrate that the adenylate cyclase activity of P. aeruginosa ExoY can reduce inflammasome-related responses by influencing both the host and the bacterium itself by delaying the activation of inflammatory pathways and suppressing bacterial motility.

Impact of immediate post-reperfusion cooling on outcome in patients with acute stroke and substantial ischemic changes.

BACKGROUND: In patients with acute stroke and an extensive ischemic burden at baseline, the prognosis is usually poor despite timely reperfusion. OBJECTIVE: To overcome universally poor outcomes in such patients, by applying immediate 'post-reperfusion cooling' in order to reduce reperfusion-related complications, and to describe the clinical and imaging characteristics. METHODS: Patients having (1) an acute anterior large vessel occlusive stroke within 4.5 h since last known well, (2) Alberta Stroke Program Early CT Score (ASPECTS) ≤5 on baseline imaging, and (3) targeted temperature management with endovascular cooling after confirmed reperfusion were included in this study. RESULTS: Eighteen patients (mean±SD age 59.5±10.9 years, median National Institutes of Health Stroke Scale score of 17, and median ASPECTS of 3) were analyzed. Median lesion volumes at baseline and after treatment were 130.2 and 110.6 mL, respectively. Median time from onset to the start of hypothermia and hypothermia duration were 213 min and 51 h, respectively. Favorable outcome (modified Rankin Scale ≤2) at 3 months was observed in 10 (55.6%) patients. Symptomatic intracranial hemorrhage, malignant brain edema, and pneumonia were observed in 2, 6, and 8 patients, respectively. CONCLUSIONS: The use of post-reperfusion cooling as a rescue treatment in patients with substantial ischemia at baseline might improve clinical outcome.

Pseudomonas aeruginosa GroEL Stimulates Production of PTX3 by Activating the NF-κB Pathway and Simultaneously Downregulating MicroRNA-9.

As one of the first lines of host defense, monocytes play important roles in clearing infected microbes. The defensive response is triggered by recognition of diverse microbial moieties, including released factors, which modulate host immune responses to establish a harsh environment for clinically important bacterial pathogens. In this study, we found that the expression of PTX3, a soluble form of pattern recognition receptor, was induced by infection with live Pseudomonas aeruginosa or treatment of cells with its supernatant. P. aeruginosa GroEL, a homolog of heat shock protein 60, was identified as one of the factors responsible for inducing the expression of PTX3 in host cells. GroEL induced PTX3 expression by activating the Toll-like receptor 4 (TLR4)-dependent pathway via nuclear factor-kappa B (NF-κB), while simultaneously inhibiting expression of microRNA-9, which targets the PTX3 transcript. Finally, by acting as an opsonin, GroEL-induced PTX3 promoted the association and phagocytosis of Staphylococcus aureus into macrophages. These data suggest that the host defensive environment is supported by the production of PTX3 in response to GroEL, which thus has therapeutic potential for clearance of bacterial infections.

Forced arterial suction thrombectomy of septic embolic middle cerebral artery occlusion due to infective endocarditis: an illustrative case and review of the literature.

In acute ischemic stroke patients with major intracranial vessel occlusion due to infective endocarditis, treatment modalities are not well established. A 40-year-old woman presented with acute stroke due to left middle cerebral artery occlusion. She was successfully treated with intra-arterial mechanical thrombectomy, and the subsequent clinical outcome was favorable. Pathological analysis of the retrieved clots showed septic thrombi containing gram-positive cocci. Based on literature review and the present case regarding treatment strategies for patients with septic embolic stroke, pharmacological thrombolysis might increase the risk of hemorrhagic complications, which might alter clinical outcome. Therefore, we can consider intra-arterial mechanical thrombectomy as a first-line treatment option in patients with acute stroke resulting from infective endocarditis.

Posterior reversible encephalopathy syndrome due to hyponatremia.

Posterior reversible encephalopathy syndrome (PRES) is characterized by variable associations of seizure activity, consciousness impairment, headaches, visual abnormalities, nausea/vomiting, and focal neurological signs. The PRES may occur in diverse situations. The findings on neuroimaging in PRES are often symmetric and predominate edema in the white matter of the brain areas perfused by the posterior brain circulation, which is reversible when the underlying cause is treated. We report the case of PRES in normotensive patient with hyponatremia.