Delayed recanalization reduced neuronal apoptosis and neurological deficits by enhancing liver-derived trefoil factor 3-mediated neuroprotection via LINGO2/EGFR/Src signaling pathway after middle cerebral artery occlusion in rats.

Delayed recanalization at days or weeks beyond the therapeutic window was shown to improve functional outcomes in acute ischemic stroke (AIS) patients. However, the underlying mechanisms remain unclear. Previous preclinical study reported that trefoil factor 3 (TFF3) was secreted by liver after cerebral ischemia and acted a distant neuroprotective factor. Here, we investigated the liver-derived TFF3-mediated neuroprotective mechanism enhanced by delayed recanalization after AIS. A total of 327 male Sprague-Dawley rats and the model of middle cerebral artery occlusion (MCAO) with permanent occlusion (pMCAO) or with delayed recanalization at 3 d post-occlusion (rMCAO) were used. Partial hepatectomy was performed within 5 min after MCAO. Leucine-rich repeat and immunoglobulin-like domain-containing nogo receptor-interacting protein 2 (LINGO2) siRNA was administered intracerebroventricularly at 48 h after MCAO. Recombinant rat TFF3 (rr-TFF3, 30 µg/Kg) or recombinant rat epidermal growth factor (rr-EGF, 100 µg/Kg) was administered intranasally at 1 h after recanalization, and EGFR inhibitor Gefitinib (75 mg/Kg) was administered intranasally at 30 min before recanalization. The evaluation of outcomes included neurobehavior, ELISA, western blot and immunofluorescence staining. TFF3 in hepatocytes and serum were upregulated in a similar time-dependent manner after MCAO. Compared to pMCAO, delayed recanalization increased brain TFF3 levels and attenuated brain damage with the reduction in neuronal apoptosis, infarct volume and neurological deficits. Partial hepatectomy reduced TFF3 levels in serum and ipsilateral brain hemisphere, and abolished the benefits of delayed recanalization on neuronal apoptosis and neurobehavioral deficits in rMCAO rats. Intranasal rrTFF3 treatment reversed the changes associated with partial hepatectomy. Delayed recanalization after MCAO increased the co-immunoprecipitation of TFF3 and LINGO2, as well as expressions of p-EGFR, p-Src and Bcl-2 in the brain. LINGO2 siRNA knockdown or EGFR inhibitor reversed the effects of delayed recanalization on apoptosis and brain expressions of LINGO2, p-EGFR, p-Src and Bcl-2 in rMCAO rats. EGFR activator abolished the deleterious effects of LINGO2 siRNA. In conclusion, our investigation demonstrated for the first time that delayed recanalization may enhance the entry of liver-derived TFF3 into ischemic brain upon restoring blood flow after MCAO, which attenuated neuronal apoptosis and neurological deficits at least in part via activating LINGO2/EGFR/Src pathway.

Laser-Triggered High Graphitization of Mo2C@C: High Rate Performance and Excellent Cycling Stability as Anode of Lithium Ion Batteries.

Fast electron/ion transport and cycling stability of anode materials are key factors for achieving a high rate performance of battery materials. Herein, we successfully fabricated a carbon-coated Mo2C nanofiber (denoted as laser Mo2C@C) as the lithium ion battery anode material by laser carbonization of PAN-PMo12 (PAN = Polyacrylonitrile; PMo12 = H3PMo12O40). The highly graphitized carbon layer in laser Mo2C@C effectively protects Mo2C from agglomeration and flaking while facilitating electron transfer. As such, the laser Mo2C@C electrode displays an excellent electrochemical stability under 5 A g-1, with a capacity up to 300 mA h g-1 after 3000 cycles. Furthermore, the extended X-ray absorption fine structure results show the existence of some Mo vacancies in Mo2C@C. Density functional theory calculations further prove that such vacancies make the defective Mo2C@C composites energetically more favorable for lithium storage in comparison with the intact Mo2C.

Incremental Value of Stroke-Induced Structural Disconnection in Predicting Global Cognitive Impairment After Stroke.

BACKGROUND: Poststroke cognitive impairment (PSCI) is highly prevalent in stroke survivors and correlated with unfavorable clinical outcomes. This study aimed to identify the neural substrate of PSCI using atlas-based disconnectome analysis and assess the value of disconnection score, a baseline measure for stroke-induced structural disconnection, in PSCI prediction. METHODS: A multicenter prospective cohort of 676 first-ever patients with acute ischemic stroke was enrolled from 3 independent hospitals in China. Sociodemographic, clinical, and neuroimaging data were collected at acute stage of stroke. Cognitive assessment was performed at 3 months after stroke. Voxel-wise and tract-wise disconnectome analysis were performed to uncover the strategic structural disconnection pattern for global PSCI. Disconnection score was calculated for each participant in leave-one-dataset-out cross-validation. Multivariable logistic regression was performed for the association between disconnection score and PSCI. Prediction models with and without disconnection score were developed, cross-validated, and compared in terms of discrimination and goodness-of-fit. RESULTS: Compared with lesions of non-PSCI, those of PSCI were more likely to have fiber connections with left prefrontal cortex and left deep structures (thalamus and basal ganglia). Disconnection score could predict the risk and severity of PSCI during cross-validation, and was independently associated with PSCI after controlling for all baseline covariates (odds ratio, 1.38 [95% CI, 1.17-1.64]; P<0.001). Incorporating disconnection score into a reference model with 6 known predictors resulted in significant improvement in both discrimination and goodness-of-fit throughout cross-validation. CONCLUSIONS: A strategic structural disconnection pattern centered on left prefrontal cortex, thalamus, and basal ganglia is identified for global PSCI using indirect disconnectome analysis. The baseline disconnection score is independently predictive of PSCI and has significant incremental value to preexisting sociodemographic, clinical, and neuroimaging predictors. REGISTRATION: URL: http://www.chictr.org.cn/enIndex.aspx; Unique identifier: ChiCTR-ROC-17013993.

Good functional outcome following bilateral external capsule hemorrhage mimicking bilateral basal ganglia hemorrhage in a coma patient.

Simultaneous spontaneous bilateral external capsule hemorrhage is a rare clinical entity with extremely poor outcome. However, knowledge on the effective management of this fatal disease is limited. Herein,we described a case of a 42-year-old man with acute coma and quadriplegia as well as respiratory failure related to the disease. The patient underwent minimally invasive surgery plus local thrombolysis. Consequently, he recovered with satisfactory neurological function recovery on the 180th day of follow-up.

Comparative study on acute management of intracerebral haematoma using local thrombolysis in moyamoya and non-moyamoya patients: a single institution experience.

PURPOSE: Spontaneous intracerebral haemorrhage (ICH) is the main presentation in adults with moyamoya disease (MMD), an unusual clinical entity with a poor prognosis. However, optimal management in the acute stage of ICH in patients with MMD remains a challenge. Since minimally invasive surgery (MIS) plus local thrombolysis has emerged as a promising strategy for ICH, we aimed to describe our experience of performing this procedure in this special population in the acute phase, while focusing on its efficacy and safety. MATERIALS AND METHODS: The medical data of patients with ICH treated with MIS and local thrombolysis between November 2013 and December 2017 were retrospectively reviewed at our institution. MMD was identified based on the angiographic images. The primary outcome was postoperative intracranial rebleeding. The secondary outcomes were 30-day mortality and 6-month outcome graded using the modified Rankin scale (mRS). Logistic regression was applied to explore independent risk factors for the above outcomes. RESULTS: A cohort of consecutive 337 ICH patients was analysed, of whom 14 (4.15%) were diagnosed with MMD. In total, 36 (11.46%) patients experienced postoperative intracranial rehaemorrhage, of which one patient had MMD. No significant difference was found between the patients with and without MMD regarding postoperative rebleeding (9.09% vs. 11.55%, p = 1.000). Additionally, the 30-day mortality of patients with MMD was 21.42% (3/14), which was not significantly different from that of non-MMD patients (10.83%; p = 0.201). Moreover, 53.8% of patients had poor outcomes at the 6-month follow-up among MMD patients, similar to 43.9% of patients without MMD (p = 0.573). The coexistence of MMD failed to show a significant association with postoperative intracranial rebleeding (p = 0.348), 30-day mortality (p = 0.211), or poor outcome at the 6-month follow-up (p = 0.450). CONCLUSION: Our findings suggest that coexistent MMD is not associated with an increased risk of postoperative rebleeding or poor outcome after local thrombolysis for ICH.

Piezo1 Mediates Inflammation in Balloon-inflated Rat Brain and its Bidirectional Mechanosensitivity.

BACKGROUND: Brain injury after intracerebral hemorrhage is extremely complicated, and the exact mechanism remains puzzling. Piezo1, a novel mammalian mechanosensitive ion channel, has been identified to play important roles in several pathologic and physiologic procedures that involve cellular mechanotransduction. However, the role of Piezo1 in hematoma compression after intracerebral hemorrhage is still unclear. MATERIALS AND METHODS: In the present study, we established a balloon-inflated brain model based on an adult male rat mimicking the pure mechanical compression of a hematoma. Then the behavioral assessment (Garcia Scale) was taken to observe the syndrome after "hematoma". Western blotting and immunofluorescence were applied to detect Piezo1 expression around lesions in rat brains. ELISA was used for quantitative analysis of inflammation factors. A statistical significance was confirmed as P value<0.05. RESULTS: Balloon compression lesions were detected in the basal ganglia region of the brain, resulting in abnormal behaviors and a significant increase in the expression of Piezo1 and proinflammatory cytokines. GsMTx4, an antagonist of Piezo1, reversed these effects. Additionally, the balloon deflation time affected behavioral function and the levels of Piezo1 and proinflammatory cytokines. CONCLUSION: These results establish the first in vivo evidence for the role of Piezo1 in blood-brain neuroinflammation after hematoma compression. Piezo1 showed "bidirectional mechanosensitivity" and therefore is a potential therapeutic target for the treatment of intracerebral hemorrhage.

Structural disconnection-based prediction of poststroke depression.

Poststroke depression (PSD) is a common complication of stroke. Brain network disruptions caused by stroke are potential biological determinants of PSD but their conclusive roles are unavailable. Our study aimed to identify the strategic structural disconnection (SDC) pattern for PSD at three months poststroke and assess the predictive value of SDC information. Our prospective cohort of 697 first-ever acute ischemic stroke patients were recruited from three hospitals in central China. Sociodemographic, clinical, psychological and neuroimaging data were collected at baseline and depression status was assessed at three months poststroke. Voxel-based disconnection-symptom mapping found that SDCs involving bilateral temporal white matter and posterior corpus callosum, as well as white matter next to bilateral prefrontal cortex and posterior parietal cortex, were associated with PSD. This PSD-specific SDC pattern was used to derive SDC scores for all participants. SDC score was an independent predictor of PSD after adjusting for all imaging and clinical-sociodemographic-psychological covariates (odds ratio, 1.25; 95% confidence interval, 1.07, 1.48; P = 0.006). Split-half replication showed the stability and generalizability of above results. When added to the clinical-sociodemographic-psychological prediction model, SDC score significantly improved the model performance and ranked the highest in terms of predictor importance. In conclusion, a strategic SDC pattern involving multiple lobes bilaterally is identified for PSD at 3 months poststroke. The SDC score is an independent predictor of PSD and may improve the predictive performance of the clinical-sociodemographic-psychological prediction model, providing new evidence for the brain-behavior mechanism and biopsychosocial theory of PSD.

Application of kNN and SVM to predict the prognosis of advanced schistosomiasis.

Predictive models for prognosis of small sample advanced schistosomiasis patients have not been well studied. We aimed to construct prognostic predictive models of small sample advanced schistosomiasis patients using two machine learning algorithms, k nearest neighbour (kNN) and support vector machine (SVM) utilising routinely available data under the government medical assistance programme. The predictive models were derived from 229 patients from Xiantao and externally validated by 77 patients of Jiayu, two county-level cities in Hubei province, China. Candidate predictors were selected according to expert opinions and literature reports, including clinical features, sociodemographic characteristics, and medical examinations results. An area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models' predictive performances. The AUC values were 0.879 for the kNN model and 0.890 for the SVM model in the training set, 0.852 for the kNN model, and 0.785 for the SVM model in the external validation set. The kNN and SVM models can be used to improve the health services provided by healthcare planners, clinicians, and policymakers.

Caspase-1: A Promising Target for Preserving Blood-Brain Barrier Integrity in Acute Stroke.

The blood-brain barrier (BBB) acts as a physical and biochemical barrier that plays a fundamental role in regulating the blood-to-brain influx of endogenous and exogenous components and maintaining the homeostatic microenvironment of the central nervous system (CNS). Acute stroke leads to BBB disruption, blood substances extravasation into the brain parenchyma, and the consequence of brain edema formation with neurological impairment afterward. Caspase-1, one of the evolutionary conserved families of cysteine proteases, which is upregulated in acute stroke, mainly mediates pyroptosis and compromises BBB integrity via lytic cellular death and inflammatory cytokines release. Nowadays, targeting caspase-1 has been proven to be effective in decreasing the occurrence of hemorrhagic transformation (HT) and in attenuating brain edema and secondary damages during acute stroke. However, the underlying interactions among caspase-1, BBB, and stroke still remain ill-defined. Hence, in this review, we are concerned about the roles of caspase-1 activation and its associated mechanisms in stroke-induced BBB damage, aiming at providing insights into the significance of caspase-1 inhibition on stroke treatment in the near future.

Higher Serum Lactic Dehydrogenase is Associated with Post-Stroke Depression at Discharge.

PURPOSE: Post-stroke depression (PSD) is one of the most common and severe psychological sequelae after stroke, negatively affecting the patient's functional outcome and quality of life. Rapidly measurable biomarkers to predict PSD are pivotal for the optimized care and allocation of healthcare resources. Lactic dehydrogenase (LDH) levels are increased in patients with central nervous system (CNS) disorders such as cerebral infarction and hypoxic-ischemic encephalopathy, which may be related to the occurrence of PSD in acute ischemic stroke (AIS) patients. This study aimed to investigate whether LDH levels on admission are associated with PSD at discharge. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted, including all consecutive AIS patients within 7 days after symptom onset from May 2018 to October 2019. According to the distribution of LDH and the number of patients, patients were divided into equal tertiles. PSD was evaluated by DSM-V criteria and the 17-item Hamilton Rating Scale for Depression (HRSD-17) at discharge. RESULTS: A total of 518 AIS patients were included. The optimal cut-off points of LDH were: lowest tertile (T1) 102-159/L, middle tertile (T2) 160-189 U/L, and upper tertile (T3) 190-520 U/L. A total of 249 patients (48.07%) were diagnosed with PSD at discharge. After adjusting for potential confounding factors, the odds ratio of T3 PSD was 1.698 (95% CI, 1.070-2.694, P=0.025), compared with T1. CONCLUSION: In summary, LDH serum levels on admission are associated with PSD at discharge. Clinicians should pay more attention to the baseline LDH level in screening for PSD at discharge.

Mitochondrial Dynamics: A Potential Therapeutic Target for Ischemic Stroke.

Stroke is one of the leading causes of death and disability worldwide. Brain injury after ischemic stroke involves multiple pathophysiological mechanisms, such as oxidative stress, mitochondrial dysfunction, excitotoxicity, calcium overload, neuroinflammation, neuronal apoptosis, and blood-brain barrier (BBB) disruption. All of these factors are associated with dysfunctional energy metabolism after stroke. Mitochondria are organelles that provide adenosine triphosphate (ATP) to the cell through oxidative phosphorylation. Mitochondrial dynamics means that the mitochondria are constantly changing and that they maintain the normal physiological functions of the cell through continuous division and fusion. Mitochondrial dynamics are closely associated with various pathophysiological mechanisms of post-stroke brain injury. In this review, we will discuss the role of the molecular mechanisms of mitochondrial dynamics in energy metabolism after ischemic stroke, as well as new strategies to restore energy homeostasis and neural function. Through this, we hope to uncover new therapeutic targets for the treatment of ischemic stroke.

Association of Satellite Sign with Postoperative Rebleeding in Patients Undergoing Stereotactic Minimally Invasive Surgery for Hypertensive Intracerebral Haemorrhage.

There are few studies regarding imaging markers for predicting postoperative rebleeding after stereotactic minimally invasive surgery (MIS) for hypertensive intracerebral haemorrhage (ICH), and little is known about the relationship between satellite sign on computed tomography (CT) scans and postoperative rebleeding after MIS. This study aimed to determine the value of the CT satellite sign in predicting postoperative rebleeding in patients with hypertensive ICH who undergo stereotactic MIS. We retrospectively examined and analysed 105 patients with hypertensive ICH who underwent standard stereotactic MIS for hematoma evacuation within 72 h following admission. Postoperative rebleeding occurred in 14 of 65 (21.5%) patients with the satellite sign on baseline CT, and in 5 of the 40 (12.5%) patients without the satellite sign. This difference was statistically significant. Positive and negative values of the satellite sign for predicting postoperative rebleeding were 21.5% and 87.5%, respectively. Multivariate logistic regression analysis verified that baseline ICH volume and intraventricular rupture were independent predictors of postoperative rebleeding. In conclusion, the satellite sign on baseline CT scans may not predict postoperative rebleeding following stereotactic MIS for hypertensive ICH.

Neurokinin Receptor 1 (NK1R) Antagonist Aprepitant Enhances Hematoma Clearance by Regulating Microglial Polarization via PKC/p38MAPK/NFκB Pathway After Experimental Intracerebral Hemorrhage in Mice.

Hematoma clearance is an important therapeutic target to improve outcome following intracerebral hemorrhage (ICH). Recent studies showed that Neurokinin receptor-1 (NK1R) inhibition exerts protective effects in various neurological disease models, but its role in ICH has not been explored. The objective of this study was to investigate the role of NK1R and its relation to hematoma clearance after ICH using an autologous blood injection mouse model. A total of 332 adult male CD1 mice were used. We found that the expression levels of NK1R and its endogenous ligand, substance P (SP), were significantly upregulated after ICH. Intraperitoneal administration of the NK1R selective antagonist, Aprepitant, significantly improved neurobehavior, reduced hematoma volume and hemoglobin levels after ICH, and promoted microglia polarization towards M2 phenotype. Aprepitant decreased phosphorylated PKC, p38MAPK, and NFκB p65, and downregulated M1 markers while upregulating M2 markers after ICH. Intracerebroventricular administration of the NK1R agonist, GR73632 or PKC agonist, phorbol 12-myristate 13-acetate (PMA) reversed the effects of Aprepitant. To demonstrate the upstream mediator of NK1R activation, we performed thrombin injection and found that it increased SP. Inhibiting thrombin suppressed SP and decreased M1 markers while increasing M2 microglia polarization. Thus, NK1R inhibition promoted hematoma clearance after ICH by increasing M2 microglial polarization via downregulating PKC/p38MAPK/NFκB signaling pathway, and thrombin may be a key upstream mediator of NK1R activation. Therapeutic interventions inhibiting NK1R signaling may be a new target for the treatment of ICH.

Kisspeptin-54 attenuates oxidative stress and neuronal apoptosis in early brain injury after subarachnoid hemorrhage in rats via GPR54/ARRB2/AKT/GSK3ß signaling pathway.

Oxidative stress-induced neuron apoptosis plays a crucial role in the early brain injury (EBI) after subarachnoid hemorrhage (SAH). Kisspeptin has been reported as antioxidant to reduce oxidative stress-induced neuronal cell death through G protein-coupled receptor 54 (GPR54). The goal of this study was to determine the neuroprotection of the Kisspeptin/GRP54 signaling pathway against EBI after SAH. Two hundred and ninety-two Sprague Dawley male rats were used and SAH was induced by the endovascular perforation. Exogenous Kisspeptin 54 (KP54) was delivered intranasally. Small interfering ribonucleic acid (siRNA) for endogenous KISS1, a selective GPR54 antagonist kisspeptin 234, or ß-arrestin 2 siRNA for ARRB2 (a functional adaptor of GPR54) were administered intracerebroventricularly. Post-SAH evaluations included neurobehavioral tests, SAH grade, Western blot, immunofluorescence, Fluoro-Jade C, TUNEL, and Nissl staining. The results showed that endogenous KISS1 knockdown aggravated but exogenous KP54 (1.0 nmol/kg) treatment attenuated neurological deficits, brain oxidative stress, and neuronal apoptosis at 24 h after SAH. The benefits of KP54 persisted to 28 days after SAH, which significantly improved cognitive function in SAH rats. The GPR54 blockade or the ARRB2 knockout offset the neuroprotective effects of KP54 in SAH rats. In conclusion, our results suggested that administration of KP54 attenuated oxidative stress, neuronal apoptosis and neurobehavioral impairments through GPR54/ARRB2/AKT/GSK3ß signaling pathway after SAH in rat. Thus, KP54 may provide an effective treatment strategy for SAH patients.

Activation of MC1R with BMS-470539 attenuates neuroinflammation via cAMP/PKA/Nurr1 pathway after neonatal hypoxic-ischemic brain injury in rats.

BACKGROUND: Microglia-mediated neuroinflammation plays a crucial role in the pathogenesis of hypoxic-ischemic (HI)-induced brain injury. Activation of melanocortin-1 receptor (MC1R) has been shown to exert anti-inflammatory and neuroprotective effects in several neurological diseases. In the present study, we have explored the role of MC1R activation on neuroinflammation and the potential underlying mechanisms after neonatal hypoxic-ischemic brain injury in rats. METHODS: A total of 169 post-natal day 10 unsexed rat pups were used. HI was induced by right common carotid artery ligation followed by 2.5 h of hypoxia. BMS-470539, a specific selective MC1R agonist, was administered intranasally at 1 h after HI induction. To elucidate the potential underlying mechanism, MC1R CRISPR KO plasmid or Nurr1 CRISPR KO plasmid was administered via intracerebroventricular injection at 48 h before HI induction. Percent brain infarct area, short- and long-term neurobehavioral tests, Nissl staining, immunofluorescence staining, and Western blot were conducted. RESULTS: The expression levels of MC1R and Nurr1 increased over time post-HI. MC1R and Nurr1 were expressed on microglia at 48 h post-HI. Activation of MC1R with BMS-470539 significantly reduced the percent infarct area, brain atrophy, and inflammation, and improved short- and long-term neurological deficits at 48 h and 28 days post-HI. MC1R activation increased the expression of CD206 (a microglial M2 marker) and reduced the expression of MPO. Moreover, activation of MC1R with BMS-470539 significantly increased the expression levels of MC1R, cAMP, p-PKA, and Nurr1, while downregulating the expression of pro-inflammatory cytokines (TNFα, IL-6, and IL-1ß) at 48 h post-HI. However, knockout of MC1R or Nurr1 by specific CRISPR reversed the neuroprotective effects of MC1R activation post-HI. CONCLUSIONS: Our study demonstrated that activation of MC1R with BMS-470539 attenuated neuroinflammation, and improved neurological deficits after neonatal hypoxic-ischemic brain injury in rats. Such anti-inflammatory and neuroprotective effects were mediated, at least in part, via the cAMP/PKA/Nurr1 signaling pathway. Therefore, MC1R activation might be a promising therapeutic target for infants with hypoxic-ischemic encephalopathy (HIE).

Nomograms to predict 2-year overall survival and advanced schistosomiasis-specific survival after discharge: a competing risk analysis.

BACKGROUND: The prognosis of patients with advanced schistosomiasis is poor. Pre-existing prognosis studies did not differentiate the causes of the deaths. The objectives were to evaluate the 2-year overall survival (OS) and advanced schistosomiasis-specific survival (ASS) in patients with advanced schistosomiasis after discharge through competing risk analysis and to build predictive nomograms. METHODS: Data was extracted from a previously constructed database from Hubei province. Patients were enrolled from September 2014 to January 2015, with follow up to January 2017. OS and ASS were primary outcome measures. Nomograms for estimating 2-year OS and ASS rates after discharge were established based on univariate and multivariate Cox regression model and Fine and Gray's model. Their predictive performances were evaluated using C-index and validated in both internal and external validation cohorts. RESULTS: The training cohort included 1487 patients with advanced schistosomiasis. Two-year mortality rate of the training cohort was 8.27% (123/1487). Competing events accounted for 26.83% (33/123). Older age, splemomegaly clinical classification, abnormal serum DBil, AST, ALP and positive HBsAg were significantly associated with 2-year OS. Older age, splemomegaly clinical classification, abnormal serum AST, ALP and positive HBsAg were significantly associated with 2-year ASS. The established nomograms were well calibrated, and had good discriminative ability, with a C-index of 0.813 (95% CI 0.803-0.823) for 2-year OS prediction and 0.834 (95% CI 0.824-0.844) for 2-year ASS prediction. Their predictive performances were well validated in both internal and external validation cohorts. CONCLUSION: The effective predictors of 2-year OS and ASS were discovered through competing risk analysis. The nomograms could be used as convenient predictive tools in clinical practice to guide follow-up and aid accurate prognostic assessment.

Modulation of Self-Separating Molecular Catalysts for Highly Efficient Biomass Transformations.

The energetically viable fabrication of stable and highly efficient solid acid catalysts is one of the key steps in large-scale transformation processes of biomass resources. Herein, the covalent modification of the classical Dawson polyoxometalate (POMs) with sulfonic acids (-SO3 H) is reported by grafting sulfonic acid groups on the POM's surface followed by oxidation of (3-mercaptopropyl)trimethoxysilane. The acidity of TBA6 -P2 W17 -SO3 H (TBA=tetrabutyl ammonium) has been demonstrated by using 31 P NMR spectroscopy, clearly indicating the presence of strong Brønsted acid sites. The presence of TBA counterions renders the solid acid catalyst as a promising candidate for phase transfer catalytic processes. The TBA6 -P2 W17 -SO3 H shows remarkable activity and selectivity, excellent stability, and great substrate compatibility for the esterification of free fatty acids (FFA) with methanol and conversion into biodiesel at 70 °C with >98 % conversion of oleic acid in 20 min. The excellent catalytic performance can be attributed to the formation of a catalytically active emulsion, which results in a uniform catalytic behavior during the reaction, leading to efficient interaction between the substrate and the active sites of the catalyst. Most importantly, the catalyst can be easily recovered and reused without any loss of its catalytic activity owing to its excellent phase transfer properties. This work offers an efficient and cost-effective strategy for large-scale biomass conversion applications.

The Incidence and Characteristics of Venous Thromboembolism in Neurocritical Care Patients: A Prospective Observational Study.

Risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is presumed to be high for neurologic intensive care unit (NICU) patients. However, exact incidences of VTE have yet to be reported. In this prospective observational study, we consecutively enrolled 126 neurocritical care patients who had an NICU stay ≥1 week with paralysis and/or unconsciousness. All patients received DVT prevention strategies. Patients were screened for VTE after 1 week of hospitalization, using venous ultrasonography and computed tomography pulmonary angiography. Following 1 week of NICU hospitalization, DVT incidence was 35.7% and PE incidence was 17.5%. Of the DVTs, 75.6% were in the muscular calf vein. Of the PEs, 22.7% were in main pulmonary arteries, while 77.3% were in branches. Approximately 96% of the DVTs and 86% of the PEs were asymptomatic. Approximately 24% of patients with DVT had a concurrent PE, while 50% of PE patients had a DVT. Paralysis, raised d-dimer on admission, and pulmonary infection were found to be independent risk factors for DVT. Paraplegia, femoral vein thrombosis, and pulmonary infection were found to be independent risk factors for PE. Despite active preventive measures, incidences of VTE in NICU patients were high. Most VTEs were asymptomatic, meaning they could have led to a missed diagnosis. Attention should be paid to the VTE events of critically ill neurological patients.

Derivation and external validation of a model to predict 2-year mortality risk of patients with advanced schistosomiasis after discharge.

To date, no risk prediction tools have been developed to identify high mortality risk of patients with advanced schistosomiasis within 2 years after discharge. We aim to derive and validate a risk prediction model to be applied in clinical practice. The risk prediction model was derived from 1487 patients from Jingzhou and externally validated by 723 patients of Huangshi, two prefecture-level cities in Hubei province, China (from September 2014 to January 2015, with follow-up to January 2017). The baseline variables were collected. The mean age [SD] was 62.89 [10.38] years for the derivation cohort and 62.95 [12.22] years for the external validation cohort. The females accounted for 36.3% and 43.7% of the derivation and validation cohorts, respectively. 8.27% patients (123/1487) in the derivation cohort and 7.75% patients (56/723) in the external validation cohort died within 2 years after discharge. We constructed 4 models based on the 7 selected variables: age, clinical classification, serum direct bilirubin (DBil), aspartate aminotransferase (AST), alkaline phosphatase (ALP), hepatitis B surface antigen (HBsAg), alpha fetoprotein (AFP) at admission. In the external validation cohort, the multivariate model including 7 variables had a C statistic of 0.717 (95% CI, 0.646-0.788) and improved integrated discrimination improvement (IDI) value and net reclassification improvement (NRI) value compared to the other reduced models. Therefore, a multivariate model was developed to predict the 2-year mortality risk for patients with advanced schistosomiasis after discharge. It could also help guide follow-up, aid prognostic assessment and inform resource allocation.

Is it dangerous to treat spontaneous intracerebral hemorrhage by minimally invasive surgery plus local thrombolysis in patients with coexisting unruptured intracranial aneurysms?

OBJECTIVES: Limited evidence supports the presumed increased frequency of hemorrhage caused by the unruptured intracranial aneurysms which coexist in patients with spontaneous intracerebral hemorrhage treated with minimally invasive surgery plus local thrombolysis. Subsequently, we sought to determine the safety of local thrombolysis for this particular subset of patients. PATIENTS AND METHODS: We reviewed the medical records of patients treated with minimally invasive surgery plus local thrombolysis for intracerebral hemorrhage between November 2013 to December 2015 in an intensive care unit of a tertiary care hospital. Depending upon the vascular images, unruptured intracranial aneurysms were identified. The primary outcome was any of postoperative intracranial rebleeding. The second outcome included the 30-day death and 6-month follow up graded by Modified Rank Scale. Blind abstractors reviewed the medical data and binary logistic regression was performed to investigate the risk factors of poor prognosis. RESULTS: We identified a cohort of consecutive 188 patients, of whom 23 (12.2%) harbored unruptured intracranial aneurysms. There were 28 aneurysms documented in this study, among which 3 were in the posterior circulation. And in total, 20 (11.3%) cases suffered from postoperative hematoma growth, of which 4 were with aneurysms. Additionally,the 30-day mortality after stroke in patients with aneurysms was 8.69% (2/23), comparable to 13.33% in without (22/165,p = 0.744). The proportion of the favorable outcome at 6-month follow-up in patients with aneurysms was comparable to that in without (47.8% versus 48.5%,p = 1.000) Insignificant associations were demonstrated between the unruptured intracranial aneurysms and postoperative intracranial rehemorrhage (p = 0.092), 30-day death(p = 0.588) and poor long-term prognosis (p = 0.332), respectively. CONCLUSION: Our findings suggest that unruptured intracranial aneurysms seem to represent no increased risks of poor outcome after local thrombolysis for intracerbral hematomas.