Association of Retinal Nerve Fiber Layer Thickness with Brain Microstructural Changes in Participants with White Matter Hyperintensities.

PURPOSE: White matter hyperintensity (WMH) is suggested to cause stroke and dementia in older adults. Retinal structural thicknesses revealed by optical coherence tomography (OCT) are associated with structural changes in the brain. We aimed to explore the association between the peripapillary retinal nerve fiber layer (RNFL) and cerebral microstructural changes in participants with white matter hyperintensities (WMH). METHODS: Seventy-four participants (37 controls, healthy control (HC), and 37 older adults with WMH) underwent retinal and brain imaging using OCT and magnetic resonance imaging (MRI) respectively. Peripapillary RNFL thickness was assessed by the OCT. Gray matter volume (GMV) was assessed from a T1-weighted MRI. White matter integrity was assessed with diffusion tensor imaging (DTI) while WMH severity was assessed with the Fazekas scale. All participants underwent a neuropsychological examination (Mini-Mental State Examination, MMSE). RESULTS: Older adults with WMH showed thinner peripapillary RNFL (p = 0.004) thickness when compared with the control group after adjusting for age, hypertension and gender. In our older adults with WMH, RNFL thickness correlated with fractional anisotropy (FA) in the superior longitudinal fasciculus (SLF) (Rho = -0.331, p < 0.001). In older adults with WMH, RNFL was significantly associated with MMSE scores (Rho = 0.422, p < 0.001) and Fazekas scores (Rho = -0.381, p = 0.022) respectively. CONCLUSIONS: We suggest neurodegeneration of peripapillary RNFL in older adults with WMH was associated with cerebral microstructural volume, impaired cerebral axonal damage, and cognitive performances. OCT metrics may provide evidence of neurodegeneration that may underpin WMH and cerebral microstructural changes in the brain. CLINICAL TRIAL REGISTRATION: This study was registered online at the China Clinical Trial Registration Center (registration number: ChiCTR-ROC-17011819).

PSD-95 inhibitor Tat-NR2B9c (NA-1) protects the integrity of the blood-brain barrier after transient middle artery occlusion in rats by downregulating matrix metalloprotease-9 and upregulating endothelial nitric oxide synthase.

BACKGROUND: Protection against ischemic stroke may be most effective when multiple components of the neurovascular unit are protected, yet current treatments target mainly neurons. Here we explored whether the PSD-95 inhibitor Tat-NR2B9c (NA-1) can protect not only neurons but also the blood-brain barrier. METHODS: Adult male Sprague-Dawley rats were randomly divided into three groups, which were subjected to either sham surgery or transient cerebral ischemia-reperfusion, after which some animals were treated with Tat-NR2B9c. The therapeutic efficacy of Tat-NR2B9c was assessed in terms of the degree of neurological deficit and cerebral infarction, integrity of the blood-brain barrier, cerebral water content, as well as expression of PSD-95, nitric oxide synthase, and matrix metalloprotease-9. RESULTS: Tat-NR2B9c (NA-1) ameliorated neurofunctional deficit, reduced cerebral infarction, mitigated blood-brain barrier injury and improved its integrity following ischemia-reperfusion, leading to less cerebral edema. These improvements were associated with upregulation of tight junction proteins in the blood-brain barrier. At the same time, Tat-NR2B9c (NA-1) downregulated neuronal nitric oxide synthase and matrix metalloprotease-9, while reversing the ischemia-induced downregulation of endothelial nitric oxide synthase in brain. We report here the first evidence that PSD-95 is expressed in vascular endothelial cells in the brain. CONCLUSION: Our experiments in a rat model of transient occlusion of the middle cerebral artery suggest that Tat-NR2B9c (NA-1) can mitigate ischemic injury to the blood-brain barrier, and that it may do so by downregulating matrix metalloprotease-9 and upregulating endothelial nitric oxide synthase.

Associations between computed tomography markers of cerebral small vessel disease and hemorrhagic transformation after intravenous thrombolysis in acute ischemic stroke patients.

Background: Hemorrhagic transformation (HT) is common among acute ischemic stroke patients after treatment with intravenous thrombolysis (IVT). We analyzed potential relationships between markers of cerebral small vessel disease (CSVD) and HT in patients after IVT. Methods: This study retrospectively analyzed computed tomography (CT) data for acute ischemic stroke patients before and after treatment with recombinant tissue plasminogen activator at a large Chinese hospital between July 2014 and June 2021. Total CSVD score were summed by individual CSVD markers including leukoaraiosis, brain atrophy and lacune. Binary regression analysis was used to explore whether CSVD markers were related to HT as the primary outcome or to symptomatic intracranial hemorrhage (sICH) as a secondary outcome. Results: A total of 397 AIS patients treated with IVT were screened for inclusion in this study. Patients with missing laboratory data (n = 37) and patients treated with endovascular therapy (n = 42) were excluded. Of the 318 patients included, 54 (17.0%) developed HT within 24-36 h of IVT, and 14 (4.3%) developed sICH. HT risk was independently associated with severe brain atrophy (OR 3.14, 95%CI 1.43-6.92, P = 0.004) and severe leukoaraiosis (OR 2.41, 95%CI 1.05-5.50, P = 0.036), but not to severe lacune level (OR 0.58, 95%CI 0.23-1.45, P = 0.250). Patients with a total CSVD burden ≥1 were at higher risk of HT (OR 2.87, 95%CI 1.38-5.94, P = 0.005). However, occurrence of sICH was not predicted by CSVD markers or total CSVD burden. Conclusion: In patients with acute ischemic stroke, severe leukoaraiosis, brain atrophy and total CSVD burden may be risk factors for HT after IVT. These findings may help improve efforts to mitigate or even prevent HT in vulnerable patients.

High ratio of C-reactive protein to albumin is associated with hemorrhagic transformation and poor functional outcomes in acute ischemic stroke patients after thrombolysis.

Background: In patients with acute ischemic stroke, hemorrhagic transformation (HT) is a common complication after intravenous thrombolysis (IVT). In this study, we evaluated the relationship between the ratio of C-reactive protein to albumin (CAR) before thrombolysis, HT, and functional outcomes in patients with acute ischemic stroke. Methods: We retrospectively analyzed data from 354 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China between July 2014 and May 2022. CAR was measured on admission, and HT was identified by cranial computed tomography (CT) within 24-36 h after treatment. Poor outcome was defined as a score on the modified Rankin Scale (mRS) > 2 at discharge. The multivariate logistic regression model was used to investigate the association between CAR, HT, and poor outcome after thrombolysis, respectively. Results: A total of 354 patients were analyzed, and their median CAR was 0.61 (interquartile range, 0.24-1.28). CAR was significantly higher in the 56 patients (15.8%) who experienced HT than in those who did not (0.94 vs. 0.56, p < 0.001), and the 131 patients (37.0%) who experienced poor outcome than in those who did not (0.87 vs. 0.43, p < 0.001). Multivariate logistic regression indicated that CAR was an independent risk factor for both HT and poor outcome. The risk of HT was significantly higher among patients whose CAR fell in the fourth quartile than among those with CAR in the first quartile (OR 6.64, 95% CI 1.83 to 24.17, p = 0.004). Patients with CAR in the third quartile were more likely to experience poor outcome (OR 3.35, 95% CI 1.32 to 8.51, p = 0.01), as were those in the fourth quartile (OR 7.33, 95% CI 2.62 to 20.50, p < 0.001), compared to patients with CAR in the first quartile. Conclusion: High ratio of C-reactive protein to albumin in individuals with ischemic stroke is associated with an increased risk of HT and poor functional outcomes after thrombolysis.

Uneven Terrain Walking with Linear and Angular Momentum Allocation.

Uneven terrain walking is hard to achieve for most child-size humanoid robots, as they are unable to accurately detect ground conditions. In order to reduce the demand for ground detection accuracy, a walking control framework based on centroidal momentum allocation is studied in this paper, enabling a child-size humanoid robot to walk on uneven terrain without using ground flatness information. The control framework consists of three controllers: momentum decreasing controller, posture controller, admittance controller. First, the momentum decreasing controller is used to quickly stabilize the robot after disturbance. Then, the posture controller restores the robot posture to adapt to the unknown terrain. Finally, the admittance controller aims to decrease contact impact and adapt the robot to the terrain. Note that the robot uses a mems-based inertial measurement unit (IMU) and joint position encoders to calculate centroidal momentum and use force-sensitive resistors (FSR) on the robot foot to perform admittance control. None of these is a high-cost component. Experiments are conducted to test the proposed framework, including standing posture balancing, structured non-flat ground walking, and soft uneven terrain walking, with a speed of 2.8 s per step, showing the effectiveness of the momentum allocation method.

High ratio of monocytes to high-density lipoprotein is associated with hemorrhagic transformation in acute ischemic stroke patients on intravenous thrombolysis.

Background: Hemorrhagic transformation (HT) is a frequent, serious complication in acute ischemic stroke patients on intravenous thrombolysis. Here we investigated whether risk of HT is associated with the ratio of monocyte count to high-density lipoprotein level (MHR). Materials and methods: Medical records were retrospectively examined for consecutive patients with acute ischemic stroke who received thrombolytic therapy. HT was diagnosed by computed tomography at 24-36 h after therapy. Potential association between MHR and HT was examined using logistic regression. Results: A total of 340 patients were analyzed, and their median MHR was 0.44 (0.31-0.59). MHR was higher in the 51 patients (15.0%) with HT than in those who did not suffer HT (0.53 vs. 0.42, P = 0.001). Multivariate logistic regression showed that, after adjusting for potential confounders, MHR was an independent risk factor for HT (OR 7.50, 95% CI 1.64 to 34.35, P = 0.009). Risk of HT was significantly higher among patients whose MHR fell in the third quartile (0.42-0.53) and the fourth quartile (> 0.53) than among those with MHR in the first quartile (< 0.31; OR 3.53, 95% CI 1.11 to 11.20, P = 0.032; OR 4.79, 95% CI 1.49 to 15.42, P = 0.009). Conclusion: High MHR may be independently associated with higher risk of HT in patients with acute ischemic stroke on intravenous thrombolysis.

Kid-size robot humanoid walking with heel-contact and toe-off motion.

Human-like features, like toe-off, heel-strike can enhance the performance of bipedal robots. However, few studies have considered the anthropomorphism of walking planning. Fewer studies have achieved their toe-off, heel-strike gait planning framework in a child-sized humanoid robot platform. This paper presents a human-like walking control framework based on the Divergent Component of Motion (DCM) com planning method that enables a child-sized humanoid robot to walk with a humanoid pattern with a speed of 0.6 s per step a strike of 30 cm. The control framework consists of three parts: the human-like gait generation of the center of mass (CoM) and swings foot trajectory, the dynamic replan in phase switch and the upper body stabilization controller. The dynamic replanning of the CoM and foot trajectory can efficiently decrease the vibration in the step-phase switch. The up-body stabilization controller can reduce the up-body swing in walking and increase the robot's stability while walking. The robot uses a mems-based inertial measurement unit (IMU) and joint position encoders to estimate the current state of the robot and use force-sensitive resistors (FSR) on the robot foot to identify the actual step phase of the robot. None of these solutions is high-cost or difficult to integrate with a child-size robot. Software simulations and walking experiments are using to verify the motion control algorithm. The effectiveness of the pattern generation and the controller can realize more human-like walking styles in a child-size robot are confirmed.

[Immunopathology and immunomodulatory roles of interleukin-12 in periodontal disease].

PURPOSE: To investigate the immunopathology and immunomodulatory roles of interleukin-12 (IL-12) in periodontal disease. METHODS: Ninety-eight patients with chronic periodontitis from January 2016 to January 2019 were enrolled and divided into mild group (30 cases), moderate group (35 cases) and severe group (33 cases) according to the severity of periodontitis; meanwhile, 30 healthy subjects who underwent periodontal examination in our hospital were selected as the control group. Clinical periodontal indicators including probing depth(PD), attachment loss(AL), plaque index(PLI), bleeding index(BI), Th cell expression (Th1, Th2, Th17) in peripheral blood, IL-12 levels in gingival crevicular fluid (GCF) and serum were measured. SPSS 20.0 software package was performed to analyze the correlation between IL-12 levels in GCF and serum and Th1, Th2, Th17, PD, AL, PLI, and BI. RESULTS: The differences of PD, PLI and BI among the groups were statistically significant(P<0.05). The levels of PD, PLI and BI in the mild, moderate and severe group were significantly higher than those in the control group (P<0.05). The difference of AL index among mild, moderate and severe group was statistically significant(P<0.05). The PD, AL, PLI, and BI in the moderate and severe group was significantly higher than those in the mild group(P<0.05), and the severe group was significantly higher than the mild group(P<0.05). Th1, Th2 and Th17 were significantly higher in the mild, moderate and severe group than in the control group(P<0.05); the moderate, severe group was significantly higher than the mild group in terms of Th1, Th2 and Th17 (P<0.05), and the severe group was significantly higher than the moderate group (P<0.05). The IL-12 levels in GCF and serum of the mild, moderate, and severe groups were significantly higher than those of the control group (P<0.05); IL-12 levels in the the moderate and severe groups were significantly higher than those in the mild group (P<0.05), and the IL-12 were significantly higher in the severe group than in the moderate group (P<0.05); IL-12 was positively correlated with PD, AL, PLI, BI, Th1, Th2 and Th17(P<0.05). H-E staining showed there were fewer lymphocytes in the mild group, more lymphocytes in the moderate group, and dense lymphocytes in the severe group with significant hemorrhage in intercellular mesenchyme. The IL-12 protein positive staining results were expressed in gingival tissue lymphocyte pulp with significant brown observed. The positive staining of IL-12 protein in the gingival tissues in the mild, moderate and severe group was significantly higher than in the control group, and the staining was aggravated with mild, moderate and severe inflammatory changes. CONCLUSIONS: IL-12 is involved in the immunoregulatory mechanism of periodontal disease and may be a key pro-inflammatory cytokine in the development of periodontitis.

Polysaccharide biosynthesis protein CapD is a novel pathogenicity-associated determinant of Haemophilus parasuis involved in serum-resistance ability.

The capD gene, encoding a polysaccharide biosynthesis protein, was identified previously as a differential gene between Haemophilus parasuis virulent strain Nagasaki and avirulent strain SW114; however, the characteristics of this gene associating with the pathogenicity of H. parasuis remain unclear. Here, the capD deletion mutant (ΔcapD) and its complement strain (C-capD) were generated in H. parasuis virulent strain SH0165. The deletion of capD gene significantly attenuated the pathogenicity of the SH0165 strain, while the complementation of this gene largely recovered the pathogenicity to piglets. Additionally, the ΔcapD strain could not be recovered from piglets after challenge, while both SH0165 and C-capD strains were recovered from most systemic sites. Moreover, the ΔcapD strain exhibited an extreme sensitivity to the complement-mediated killing compared with SH0165 strain, while its serum-resistance ability largely restored with the capD gene complementation. These data present the evidence that the capD gene is a novel pathogenicity-associated determinant and involved in serum-resistance ability of H. parasuis.