Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition.

Intestinal microbiota and their metabolites affect systemic inflammation and kidney disease outcomes. Here, we investigated the key metabolites associated with the acute kidney injury (AKI)-to chronic kidney disease (CKD) transition and the effect of antibiotic-induced microbiota depletion (AIMD) on this transition. In 61 patients with AKI, 59 plasma metabolites were assessed to determine the risk of AKI-to-CKD transition. An AKI-to-CKD transition murine model was established four weeks after unilateral ischemia-reperfusion injury (IRI) to determine the effects of AIMD on the gut microbiome, metabolites, and pathological responses related to CKD transition. Human proximal tubular epithelial cells were challenged with CKD transition-related metabolites, and inhibitory effects of NADPH oxidase 2 (NOX2) signals were tested. Based on clinical metabolomics, plasma trimethylamine N-oxide (TMAO) was associated with a significantly increased risk for AKI-to-CKD transition [adjusted odds ratio 4.389 (95% confidence interval 1.106-17.416)]. In vivo, AIMD inhibited a unilateral IRI-induced increase in TMAO, along with a decrease in apoptosis, inflammation, and fibrosis. The expression of NOX2 and oxidative stress decreased after AIMD. In vitro, TMAO induced fibrosis with NOX2 activation and oxidative stress. NOX2 inhibition successfully attenuated apoptosis, inflammation, and fibrosis with suppression of G2/M arrest. NOX2 inhibition (in vivo) showed improvement in pathological changes with a decrease in oxidative stress without changes in TMAO levels. Thus, TMAO is a key metabolite associated with the AKI-to-CKD transition, and NOX2 activation was identified as a key regulator of TMAO-related AKI-to-CKD transition both in vivo and in vitro.

Chemokine (C-C Motif) Ligand 8 and Tubulo-Interstitial Injury in Chronic Kidney Disease.

Kidney fibrosis has been accepted to be a common pathological outcome of chronic kidney disease (CKD). We aimed to examine serum levels and tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with CKD and to investigate their association with kidney fibrosis in CKD model. Serum levels and tissue expression of CCL8 significantly increased with advancing CKD stage, proteinuria level, and pathologic deterioration. In Western blot analysis of primary cultured human tubular epithelial cells after induction of fibrosis with rTGF-ß, CCL8 was upregulated by rTGF-ß treatment and the simultaneous treatment with anti-CCL8 mAb mitigated the rTGF-ß-induced an increase in fibronectin and a decrease E-cadherin and BCL-2 protein levels. The antiapoptotic effect of the anti-CCL8 mAb was also demonstrated by Annexin V/propidium iodide staining assay. In qRT-PCR analysis, mRNA expression levels of the markers for fibrosis and apoptosis showed similar expression patterns to those observed by western blotting. The immunohistochemical analysis revealed CCL8 and fibrosis- and apoptosis-related markers significantly increased in the unilateral ureteral obstruction model, which agrees with our in vitro findings. In conclusion, CCL8 pathway is associated with increased risk of kidney fibrosis and that CCL8 blockade can ameliorate kidney fibrosis and apoptosis.

A fast minimum variance beamforming method using principal component analysis.

Minimum variance (MV) beamforming has been studied for improving the performance of a diagnostic ultrasound imaging system. However, it is not easy for the MV beamforming to be implemented in a real-time ultrasound imaging system because of the enormous amount of computation time associated with the covariance matrix inversion. In this paper, to address this problem, we propose a new fast MV beamforming method that almost optimally approximates the MV beamforming while reducing the computational complexity greatly through dimensionality reduction using principal component analysis (PCA). The principal components are estimated offline from pre-calculated conventional MV weights. Thus, the proposed method does not directly calculate the MV weights but approximates them by a linear combination of a few selected dominant principal components. The combinational weights are calculated in almost the same way as in MV beamforming, but in the transformed domain of beamformer input signal by the PCA, where the dimension of the transformed covariance matrix is identical to the number of some selected principal component vectors. Both computer simulation and experiment were carried out to verify the effectiveness of the proposed method with echo signals from simulation as well as phantom and in vivo experiments. It is confirmed that our method can reduce the dimension of the covariance matrix down to as low as 2 × 2 while maintaining the good image quality of MV beamforming.

Predictors of 30-day mortality and 90-day functional recovery after primary intracerebral hemorrhage : hospital based multivariate analysis in 585 patients.

OBJECTIVE: The purpose of this study was to identify independent predictors of mortality and functional recovery in patients with primary intracerebral hemorrhage (PICH) and to improve functional outcome in these patients. METHODS: Data were collected retrospectively on 585 patients with supratentorial PICH admitted to the Stroke Unit at our hospital between 1st January 2004 and the 31st July 2008. Using multivariate logistic regression analysis, the associations between all selected variables and 30-day mortality and 90-day functional recoveries after PICH was evaluated. RESULTS: Ninety-day functional recovery was achieved in 29.1% of the 585 patients and 30-day mortality in 15.9%. Age (OR=7.384, p=0.000), limb weakness (OR=6.927, p=0.000), and hematoma volume (OR=5.293, p=0.000) were found to be powerful predictors of 90-day functional recovery. Furthermore, initial consciousness (OR=3.013, p=0.014) hematoma location (lobar, OR=2.653, p=0.003), ventricular extension of blood (OR=2.077, p=0.013), leukocytosis (OR=2.048, p=0.008), alcohol intake (drinker, OR=1.927, p=0.023), and increased serum aminotransferase (OR=1.892, p=0.035) were found to be independent predictors of 90-day functional recovery after PICH. On the other hand, a pupillary abnormality (OR=4.532, p=0.000) and initial unconsciousness (OR=3.362, p=0.000) were found to be independent predictors of 30-day mortality after PICH. CONCLUSION: The predictors of mortality and functional recovery after PICH identified during this analysis may assist during clinical decision-making, when advising patients or family members about the prognosis of PICH and when planning intervention trials.

Predictors for functional recovery and mortality of surgically treated traumatic acute subdural hematomas in 256 patients.

OBJECTIVE: The purpose of this study was to investigate the reliable factors influencing the surgical outcome of the patients with traumatic acute subdural hematoma (ASDH) and to improve the functional outcome of these patients. METHODS: A total of 256 consecutive patients who underwent surgical intervention for traumatic ASDH between March 1998 and March 2008 were reviewed. We evaluated the influence of perioperative variables on functional recovery and mortality using multivariate logistic regression analysis. RESULTS: Functional recovery was achieved in 42.2% of patients and the overall mortality was 39.8%. Age (OR=4.91, p=0.002), mechanism of injury (OR=3.66, p=0.003), pupillary abnormality (OR=3.73, p=0.003), GCS score on admission (OR=5.64, p=0.000), and intraoperative acute brain swelling (ABS) (OR=3.71, p=0.009) were independent predictors for functional recovery. And preoperative pupillary abnormality (OR=2.60, p=0.023), GCS score (OR=4.66, p=0.000), and intraoperative ABS (OR=4.16, p=0.001) were independent predictors for mortality. Midline shift, thickness and volume of hematoma, type of surgery, and time to surgery showed no independent association with functional recovery, although these variables were correlated with functional recovery in univariate analyses. CONCLUSION: Functional recovery was more likely to be achieved in patients who were under 40 years of age, victims of motor vehicle collision and having preoperative reactive pupils, higher GCS score and the absence of ABS during surgery. These results would be helpful for neurosurgeon to improve outcomes from traumatic acute subdural hematomas.