A pivotal role of selective autophagy in mitochondrial quality control: Implications for zinc oxide nanoparticles induced neurotoxicity.

Excessive occupational, medical, and environmental exposure of zinc oxide nanoparticles (ZnONPs) caused its accumulation in the nervous system and raised global concerns over its detrimental effects. However, very few researches had been conducted on the impact of mitochondrial quality control process on central nervous system (CNS) after ZnONPs administration, including mitochondrial fission, fusion, biogenesis, and autophagy. In present study, mitochondrial dysfunction and apoptosis were triggered in ZnONPs-exposed human neuroblastoma SH-SY5Y cells. Upregulation of mitochondrial biogenesis regulator (PGC-1α) and fission proteins (Drp1) and downregulation of fusion proteins (OPA1 and Mfn2) were observed in 3 and 6 µg/mL ZnONPs-treated cells. Meanwhile, loss of mitochondrial dynamics and biogenesis was observed in the severe impaired cells (treated with 12 µg/mL ZnONPs). More, autophagy and mitophagy were significantly activated in ZnONPs-treated cells. The increased Beclin1 and LC3 II proteins, decreases of p62 protein, and activated PINK1/Parkin signaling were quantified. The autophagy agonist (Rapamycin), inhibitor (3-MA), and mitophagy inhibitor (Cyclosporine A, CsA) were employed to verify the roles of autophagy and mitophagy in ZnONPs-treated cells. Consequently, mitochondrial dysfunction and apoptosis were aggravated by the blockage of autophagy and mitophagy. Our research could be used to evaluate the risk assessment of ZnONPs exposure in CNS neurons so as to provide a crucial guideline for their future biological applications.

Rare hand mass: malignant peripheral nerve sheath tumor.

.

Effects of nanoparticle size on the interaction between zinc oxide nanoparticles and bovine serum albumin.

Communicated by Ramaswamy H. Sarma.

Selenium nanoparticles fabricated in laminarin polysaccharides solutions exert their cytotoxicities in HepG2 cells by inhibiting autophagy and promoting apoptosis.

Selenium nanoparticles (SeNPs) have been attracting increasing attention as potential cancer therapeutic agents. In the present study, laminarin polysaccharides (LP) decorated selenium nanoparticles (LP-SeNPs) with an average diameter of ca. 60 nm were synthesized. Transmission electron microscope (TEM), laser particle analyzer, UV-visible spectrometer and Energy dispersive X-ray (EDX) spectrometer were applied to characterize the prepared SeNPs. The cytotoxicity, apoptosis, and autophagy were examined using a series of cellular assays. The results revealed that LP-SeNPs exhibited cytotoxicity against HepG2 cells with IC50 value was 23.4 ±â€¯2.7 µM. After cells were treated with various concentrations of LP-SeNPs (10, 20 and 40 µM) for 24h, the total apoptosis rate increased to 17.4 ±â€¯1.6, 20.9 ±â€¯1.3 and 30.9 ±â€¯1.2%, respectively. Additionally, treatment of LP-SeNPs increased the expression of Bax and cleaved caspase-9 but decreased the level of Bcl-2. This suggested that LP-SeNPs induced mitochondria-mediated apoptosis. Further, exposure of cells to LP-SeNPs for 12 h induced the upregulation of LC3-II and p62. Treatment of chloroquine (CQ), the inhibitors of the autophagosome, resulted in further accumulation of p62 and LC3-II. These results demonstrated that LP-SeNPs induced the activation of early autophagy, but blocked the late phase of autophagy. Inhibition of late phase of autophagy resulted in the damaged organelles cannot be cleared and aggravating apoptosis. In conclusion, these results indicated that LP-SeNPs exerted its cytotoxicity in HepG2 cells by inhibiting autophagy and inducing apoptosis.

Green synthesis of selenium nanoparticles with extract of hawthorn fruit induced HepG2 cells apoptosis.

CONTEXT: Selenium nanoparticles (SeNPs) have attracted worldwide attention due to their unique properties and potential bioactivities. Considering that hawthorn is both a traditional medicine and a common edible food, hawthorn fruit extract (HE) was chosen as a reductant to prepare SeNPs. OBJECTIVE: SeNPs were synthesized by using an aqueous HE as a reductant and stabilizer. The antitumor activities and potential mechanisms of SeNPs were explored by using a series of cellular assays. MATERIALS AND METHODS: The HE mediated SeNPs (HE-SeNPs) were examined using various characterisation methods. The cytotoxicity was measured against HepG2 cells after treated with 0, 5, 10 and 20 µg/mL of HE-SeNPs for 24 h. Annexin V-FITC/PI staining analysis was performed to observe the apoptosis of HepG2 cells. Additionally, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels were evaluated. Finally, the protein expression levels of caspase-9 and Bcl-2 were identified by Western blot. RESULTS: The mono-dispersed and stable SeNPs were prepared with an average size of 113 nm. HE-SeNPs showed obvious antitumor activities towards HepG2 cells with an IC50 of 19.22 ± 5.3 µg/mL. Results from flow cytometry revealed that both early and total apoptosis rates increased after treating with HE-SeNPs. After cells were treated with various concentrations of HE-SeNPs (5, 10 and 20 µg/mL) for 24 h, the total rate increased to 7.3 ± 0.5, 9.7 ± 1.7 and 19.2 ± 1.6%, respectively. Meanwhile, treatment of HE-SeNPs up-regulated intracellular ROS levels and reduced the MMP. In addition, HE-SeNPs induced the up-regulation of caspase-9 and down-regulation of Bcl-2. DISCUSSION AND CONCLUSIONS: HE-SeNPs induced intracellular oxidative stress and mitochondrial dysfunction to initiate HepG2 cell apoptosis through the mitochondrial pathway. Therefore, HE-SeNPs may be a candidate for further evaluation as a chemotherapeutic agent for human liver cancer.

Cerebral Venous Malformations in a Chinese Population: Clinical Manifestations, Radiological Characteristics, and Long-Term Prognosis.

OBJECTIVE: We elucidated the clinical and radiological characteristics and analyzed the risk factors for hemorrhage and poor outcomes of cerebral venous malformations (CVMs) in a northern Chinese population. METHODS: We included 60 consecutive patients with CVM patients in Beijing Tiantan Hospital from January 2011 to February 2018. The clinical manifestations, radiological characteristics, management, and outcomes were elucidated and analyzed. The patients were followed up for 5-64 months (median, 26). Poor outcomes included repeat bleeding, secondary infarction, severe disability (modified Rankin scale score ≥3), and death. RESULTS: Infratentorial CVMs were more prone to intracranial hemorrhage (75% vs. 28.6%; P < 0.001), dizziness (37.5% vs. 10.7%; P = 0.017), and focal neurological deficits (65.6% vs. 25%; P = 0.002) than were supratentorial CVMs. Supratentorial CVMs were more prone to seizure (32.1% vs. 0%; P = 0.001) than were infratentorial CVMs. Multivariate logistic regression revealed that the major risk factors for intracranial hemorrhage in CVMs were infratentorial lesions (P = 0.003) and complicated cavernous angiomas (P = 0.016). Compared with conservative treatment, resection of hematoma or cavernous angiomas with CVM preservation did not increase the risk of poor outcomes (P = 0.646). However, CVM resection significantly increased that risk (odds ratio, 44.0; P = 0.003). CONCLUSIONS: Our results have shown that conservative treatment of CVMs results in a relatively good prognosis. For those complicated by hemorrhage or cavernous angiomas requiring surgical interventions, the integrity of the CVM should be preserved, irrespective of the treatment. In exceptional cases, before CVM resection, the CVM drainage should be comprehensively evaluated.

Synthesis, characterization and antitumor properties of selenium nanoparticles coupling with ferulic acid.

Selenium nanoparticles (Se NPs) attract a lot of attention as potential cancer therapeutic agents. However, the antitumor activities of pure Se NPs are poor, and some modifiers are needed to enhance the activities. In the present study, we prepared Ferulic Acid (FA)-modified selenium nanoparticles in a facile synthetic approach. The obtained FA-Se NPs were characterized using transmission electron microscope (TEM), dynamic light scattering (DLS), ultraviolet-visible spectrophotometer (UV-VIS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Energy dispersive X-ray (EDX) spectroscopy. In vitro antitumor effects of FA, Se NPs and FA-Se NPs in HepG-2 cells were examined by methyl thiazolyl tetrazolium (MTT) assay. It showed that FA-Se NPs effectively inhibited the growth of HepG-2 cells with IC50 value of 11.57 ±â€¯3.6 µg/ml, while the value of Se NPs was >100 µg/ml. In addition, FA behaves no obvious antitumor effects at high concentrations up to 100 µg/ml. In order to investigate the antitumor mechanism of FA-Se NPs, fluorescence morphological examination and Annexin V-FITC/PI staining analysis were performed to observe the apoptosis of HepG-2 cells induced by FA-Se NPs. Meanwhile, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels and caspase-3 and -9 activities were detected. The results revealed that FA-Se NPs induced intracellular ROS generation and MMP disruption by finally activating caspase-3/9 to trigger HepG-2 cells apoptosis through mitochondrial pathway. Further investigation on the interactions of FA-Se NPs with calf thymus DNA (ctDNA) indicated that the antitumor activities may be associated with the DNA-binding properties of FA-Se NPs.

Global spatial risk pattern of highly pathogenic avian influenza H5N1 virus in wild birds: A knowledge-fusion based approach.

Highly pathogenic avian influenza (HPAI) H5N1 viruses have continuously circulated throughout much of the world since 2003, resulting in huge economic losses and major public health problems. Wild birds have played an important role in the spread of H5N1 HPAI. To understand its spatial distribution, H5N1 HPAI have been studied by many disciplines from different perspectives, but only one kind of disciplinary knowledge was involved, which has provided limited progress in understanding. Combining risk information from different disciplines based on knowledge fusion can provide more accurate and detailed information. In this study, local k function, phylogenetic tree analysis, and logistic spatial autoregressive models were used to explore the global spatial pattern of H5N1 HPAI based on outbreak data in wild birds, genetic sequences, and risk factors, respectively. On this basis, Dempster-Shafer (D-S) evidence theory was further applied to study the spatial distribution of H5N1 HPAI. We found D-S evidence theory was more robust and reliable than the other three methods, providing technical and methodological support for application to the research of other diseases. The shortest distance to wild bird migration routes, roads and railways, elevation, the normalized difference vegetation index (NDVI), land use and land cover (LULC) and infant mortality rates (IMR) were significantly associated with the occurrence of H5N1 HPAI. The high-risk areas were mainly located in Northern and Central Europe, the eastern Mediterranean, and East and Southeast Asia. High-risk clusters were closely related to the social, economic and ecological environment of the region. Locations where the potential transmission risk remains high should be prioritized for control efforts.

Shear Stress Induces Phenotypic Modulation of Vascular Smooth Muscle Cells via AMPK/mTOR/ULK1-Mediated Autophagy.

Phenotypic modulation of vascular smooth muscle cells (VSMCs) is involved in the pathophysiological processes of the intracranial aneurysms (IAs). Although shear stress has been implicated in the proliferation, migration, and phenotypic conversion of VSMCs, the molecular mechanisms underlying these events are currently unknown. In this study, we investigated whether shear stress(SS)-induced VSMC phenotypic modulation was mediated by autophagy involved in adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/Unc-51-like kinase 1 (ULK1) pathway. The results show that shear stress could inhibit the expression of key VSMC contractile genes and induce pro-inflammatory/matrix-remodeling genes levels, contributing to VSMCs phenotypic switching from a contractile to a synthetic phenotype. More importantly, Shear stress also markedly increased the levels of the autophagy marker microtubule-associated protein light chain 3-II (LC3II), Beclin-1, and p62 degradation. The autophagy inhibitor 3-methyladenine (3-MA) significantly blocked shear-induced phenotypic modulation of VSMCs. To further explore the molecular mechanism involved in shear-induced autophagy, we found that shear stress could activate AMPK/mTOR/ULK1 signaling pathway in VSMCs. Compound C, a pharmacological inhibitor of AMPK, significantly reduced the levels of p-AMPK and p-ULK, enhanced p-mTOR level, and finally decreased LC3II and Beclin-1 level, which suggested that activated AMPK/mTOR/ULK1 signaling was related to shear-mediated autophagy. These results indicate that shear stress promotes VSMC phenotypic modulation through the induction of autophagy involved in activating the AMPK/mTOR/ULK1 pathway.

Suppression of FoxO3a attenuates neurobehavioral deficits after traumatic brain injury through inhibiting neuronal autophagy.

Traumatic brain injury (TBI) is a serious insult that frequently leads to neurological impairments. Forkhead box O (FoxO) 3a, as transcription factor, has been confirmed to modulate autophagic process. Moreover, FoxO3a is expressed throughout the brain including the hippocampus. However, the role of FoxO3a in the pathophysiology of TBI is unclear. The present study is designed to investigate whether FoxO3a has the neuroprotective effects on rats subjected to TBI, and further to explore the potential molecular mechanisms. Thus, a rat model of TBI was created by using a modified weight-drop device to mimic the insults of TBI. The results showed that FoxO3a was significantly increased in the serum of patients with TBI as well as in experimental animals. Furthermore, our data also demonstrated that TBI stimulated the translocation of FoxO3a from the cytosol to the nucleus. Additionally, we found that knockdown of FoxO3a by siRNA silencing significantly improved neurobehavioral dysfunctions and conferred a better neuroprotective effects after TBI, evidenced by promoting motor behavioral recovery, attenuating learning and memory impairments, and partially reversing neuronal damage in the hippocampus. To further investigate the molecular mechanisms underlying this neuroprotection, we identified that nuclear accumulation of Foxo3a could induce highly expression of autophagy pathway genes including LC-3, Beclin-1, p62, ATG12, and ATG14, and finally initiate neurological impairments. Interestingly, silencing FoxO3a by siRNA remarkably inhibited the induction of neuronal autophagy after TBI, and activated autophagy was closely related to TBI-induced neurological deficits. Taken together, these findings indicated that FoxO3a knockdown conferred neuroprotective effects after TBI through inhibiting the activation of neuronal autophagy.

miR-23b improves cognitive impairments in traumatic brain injury by targeting ATG12-mediated neuronal autophagy.

Dysregulated microRNAs (miRNAs) have been reported to involve in the pathophysiological process of traumatic brain injury (TBI), and modulate autophagy-related genes (ATGs) expression. Our previous studies showed that neuronal autophagy was activated in the injury hippocampus post- TBI and associated with neurological and cognitive impairments. The present study was designed to investigate the possible role of miR-23b in TBI-induced cognitive impairments. We found the overexpression of miR-23b conferred a better neuronprotective effects after TBI by decreasing lesion volume, alleviating brain edema, inhibiting neuron apoptosis and attenuating long-term neurological deficits, and most interestingly, improving cognitive impairments. To further explore the molecular underlying this neuronprotection, we evaluated autophagic activity and ATG12 expression in the injury hippocampus CA1 region. The results identified that miR-23b directly targeted to the 3'UTR region of ATG12 mRNA to suppress the activation of neuronal autophagy by a dual-luciferase reporter system. Notably, overexpression of ATG12 abrogated the neuronprotective effects of miR-23b on TBI-induced neurological and cognitive impairments. Taken together, these date revealed inhibition of ATG12-mediated autophagic activity by miR-23b overexpression might be involve in cognitive improvement after TBI, indicating that miR-23b might be a potential therapeutic target for TBI.

MiR-144 promotes ß-amyloid accumulation-induced cognitive impairments by targeting ADAM10 following traumatic brain injury.

The dysregulation expression of microRNAs (miRNAs) including miR-144, has been widely documented in TBI. However, little is known about the potential roles of miR-144 in the pathogenesis of TBI. In this study, we investigated the potential effects of miR-144 on cognitive function in vivo and in vitro. The results indicated that inhibition of miR-144 conferred a better neurological outcome after TBI in vivo, as evidenced by reduced lesion volume, alleviated brain edema and increased mNSS, of particular importance, improved cognitive deficits. In vitro, miR-144 knockdown protected neuron against Glu-induced injury, by enhancing cell viability, suppressing LDH release and caspase-3 activity, and reducing cognitive-related proteins levels. However, overexpression of miR-144 in vivo and in vitro showed the opposite effects. To further explore the molecular mechanisms underlying miR-144-induced cognitive dysfunctions, we found a significant inverse correlation between miR-144 and ADAM10 expression. Moreover, the direct interaction between miR-144 and ADAM10 3'-UTR was identified by dual-luciferase reporter assay. Also, we found miR-144 negatively regulated ADAM10 protein expression. Additionally, ADAM10 could modulate ß-amyloid formation involved in cognitive deficits. Notably, ADAM10 knockdown by siRNA apparently abrogated miR-144 inhibitor-mediated neuroprotection. Taken together, these findings demonstrated that elevated miR-144 promoted cognitive impairments induced by ß-amyloid accumulation post-TBI through suppressing of ADAM10 expression.

Synthesis and cytotoxic activities of novel 4-methoxy-substituted and 5-methyl-substituted (3'S,4'S)-(-)-cis-khellactone derivatives that induce apoptosis via the intrinsic pathway.

This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3'S,4'S)-(-)-cis-khellactones. The newly synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C-NMR, mass spectrometry, and elemental analysis. All the derivatives were subjected to in vitro cytotoxicity screening against HEPG-2 (human liver carcinoma), SGC-7901 (human gastric carcinoma), and LS174T (human colon carcinoma), by using the MTT assay. The results revealed that several of the 4-methoxy-substituted compounds exhibited potent cytotoxicity. Among these, compound 12e showed the highest activity against cancer cells which 50% inhibitory concentration (IC50) values were in the range of 6.1-9.2 µM with low toxicity on normal human hepatocyte. Preliminary investigation of possible mechanisms of action of compound 12e against HEPG-2 cells indicated possible induction of apoptosis, as determined by morphological observations and Annexin V/propidium iodide (PI) double staining, in addition to apparent dissipation of mitochondrial membrane potential (MMP), as measured by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining in combination with the activation of caspase-9 and caspase-3 by Western blot analysis. Overall, the data suggest that compound 12e may be a promising potential anti-cancer agent that could act primarily by inducing apoptosis through the mitochondria-mediated intrinsic pathway in human hepatoma cells.

Risk Factors to Predict Neurologic Complications After Endovascular Treatment of Unruptured Paraclinoid Aneurysms.

OBJECTIVE: Unruptured paraclinoid aneurysms are often asymptomatic, and endovascular coiling is the main treatment. However, endovascular treatment of these lesions still leads to neurologic complications. We aimed to identify predictors of neurologic complications in these lesions. METHODS: We retrospectively analyzed patients with unruptured paraclinoid aneurysms who were treated with endovascular coiling between January 2014 and December 2015. A neurologic complication was defined as any transient or permanent increase in the modified Rankin Scale score after aneurysm embolization. Univariate and mulitivariate logistic regression analyses were performed to assess the risk factors of neurologic complications. RESULTS: Of the 443 unruptured paraclinoid aneurysms that were included in this study, the incidence of neurologic complications was 5.2%. Neurologic complications were highly correlated with hypertension (odds ratio [OR], 3.147; 95% confidence interval [CI], 1.217-8.138; P = 0.018), cerebral ischemic comorbidities (OR, 3.396; 95% CI, 1.378-8.374; P = 0.008), and aneurysm size (OR, 7.714; 95% CI, 1.784-31.635; P < 0.001), and irregular shape (OR, 3.157; 95% CI, 1.239-8.043; P = 0.016) in the univariate analysis. Cerebral ischemic comorbidities (OR, 2.837, 95% CI, 1.070-7.523; P = 0.036) and aneurysm size as dichotomous variables (OR, 7.557; 95% CI, 2.975-19.198; P < 0.001) were strongly correlated with neurologic complications in the final adjusted multivariate logistic analysis. CONCLUSIONS: Unruptured paraclinoid aneurysms after endovascular treatments had 5.2% of neurologic complications. Cerebral ischemic comorbidities and aneurysm size were predictors of neurologic complications.

MiR-29b Downregulation Induces Phenotypic Modulation of Vascular Smooth Muscle Cells: Implication for Intracranial Aneurysm Formation and Progression to Rupture.

BACKGROUND/AIMS: Our previous microarray results identified numerous microRNAs (miRNAs), including miR-29b, that were differentially expressed in the serum of intracranial aneurysm (IA) patients. The current study aimed to investigate whether miR-29b downregulation in IA could promote the phenotypic modulation of vascular smooth muscle cells (VSMCs) involved in the pathogenesis of aneurysm by activating ATG14-mediated autophagy. METHODS: First, the levels of miR-29b and autophagy related genes (ATGs) between IA patients and normal subjects were compared. Next, we modified the level of miR-29b via lentivirus particles in the VSMCs and examined the effects of miR-29b on proliferation, migration, and phenotypic modulation of VSMCs from a contractile phenotype to a synthetic phenotype, as well as the levels of autophagy. Finally, the binding of miR-29b to the 3'UTR of ATG14 mRNA and its effects on ATG14 expression were analysed by a luciferase reporter assay and Western blot, respectively. RESULTS: The level of miR-29b was decreased, and autophagy markers were increased in the IA patients compared to that of the normal subjects. Knockdown of miR-29b significantly promoted VSMCs proliferation and migration and, more importantly, induced the phenotypic modulation associated with autophagy activation, whereas miR-29b overexpression showed the opposite effects. The luciferase reporter assay demonstrated that ATG14 was a functional target gene of miR-29b. Notably, knockdown of ATG14 by siRNA apparently abrogated miR-29b inhibition-mediated phenotypic modulation. CONCLUSION: Downregulation of miR-29b induced VSMCs phenotypic modulation by directly activating ATG14-mediated autophagy, which is associated with the formation, growth and rupture of IAs.

Neuroprotective effects of miR-27a against traumatic brain injury via suppressing FoxO3a-mediated neuronal autophagy.

MicroRNA-27a (miR-27a) has been reported to be a brain-specific miRNA and aberrantly expressed in the brain suffered from traumatic brain injury (TBI). The present study is designed to investigate the potential role and molecular mechanism of miR-27a in the pathogenesis of TBI. The level of miR-27a in brain was manipulated by intracerebroventricular injection of lentiviral-encoding miR-27a before TBI induction. Real-time PCR was used to detected miR-27a and Forkhead box O3a (FoxO3a) levels in the hippocampus. Then, we evaluated the impact of miR-27a overexpression on neurological function, brain edema, lesion volume and neuronal autophagy after TBI. The blinding of miR-27a to the 3'UTR of FoxO3a mRNA and its effects on FoxO3a translation were analyzed by luciferase reporter assay and Western blot. The downregulation of miR-27a and the increase in FoxO3a level were observed in the hippocampus post-TBI. Overexpression of miR-27a significantly attenuated neurological deficits and brain injury, especially suppressed autophagic activation after TBI. Furthermore, we identified that miR-27a directly targeted the FoxO3a 3'UTR region to reduced FoxO3a protein expression. Knockdown of FoxO3a significantly reversed high levels of autophagy-related genes induced by TBI. Taken together, Overexpression of miR-27a may protect against brain injury via suppressing FoxO3a-mediated neuronal autophagy following TBI.

Monitoring schistosomiasis risk in East China over space and time using a Bayesian hierarchical modeling approach.

Schistosomiasis remains a major public health problem and causes substantial economic impact in east China, particularly along the Yangtze River Basin. Disease forecasting and surveillance can assist in the development and implementation of more effective intervention measures to control disease. In this study, we applied a Bayesian hierarchical spatio-temporal model to describe trends in schistosomiasis risk in Anhui Province, China, using annual parasitological and environmental data for the period 1997-2010. A computationally efficient approach-Integrated Nested Laplace Approximation-was used for model inference. A zero-inflated, negative binomial model best described the spatio-temporal dynamics of schistosomiasis risk. It predicted that the disease risk would generally be low and stable except for some specific, local areas during the period 2011-2014. High-risk counties were identified in the forecasting maps: three in which the risk remained high, and two in which risk would become high. The results indicated that schistosomiasis risk has been reduced to consistently low levels throughout much of this region of China; however, some counties were identified in which progress in schistosomiasis control was less than satisfactory. Whilst maintaining overall control, specific interventions in the future should focus on these refractive counties as part of a strategy to eliminate schistosomiasis from this region.

Larger inflow angle and incomplete occlusion predict recanalization of unruptured paraclinoid aneurysms after endovascular treatment.

BACKGROUND: Unruptured paraclinoid aneurysms have a high incidence of aneurysm recanalization (AR) after endovascular treatment. We aimed to identify the incidence and predictors of AR in these lesions. METHODS: We retrospectively analyzed consecutive patients with unruptured paraclinoid aneurysms who underwent endovascular treatment between January 2013 and December 2014. Patients with fusiform aneurysms, dissection aneurysms, traumatic aneurysms, or without digital subtraction angiography (DSA) at follow-up, were excluded. AR was defined as any aneurysm remnant that had increased in size or contrast filling that was observed via DSA at the follow-up. Univariate and multivariate logistic regression analyses were performed to assess the predictors of AR. RESULTS: We included 145 patients with 150 unruptured paraclinoid aneurysms in the analysis. The incidence of AR was 8.7% (95% confidence interval (CI): 4.7-13.3%) at a mean follow-up of 7.4 months. In the univariate analysis, AR was associated with aneurysm size (odd ratio (OR): 6.098; 95% CI: 1.870-19.886; p = 0.003), location (OR: 3.88; 95% CI: 1.196-12.583; p = 0.024), inflow angle (OR: 6.852; 95% CI: 1.463-32.087; p = 0.015), and Raymond scale (OR: 12.473; 95% CI: 2.7496-56.59; p < 0.001). In the adjusted multivariate analysis, AR was independently predicted by Raymond scale (OR: 9.136; 95% CI: 1.683-49.587; p = 0.001) and inflow angle (OR: 16.159; 95% CI: 3.211-81.308; p = 0.01). CONCLUSIONS: Unruptured paraclinoid aneurysms had a high incidence of AR after endovascular treatment. An inflow angle of ≥90 degrees and incomplete occlusion were significant predictors of AR.

Risk Score for Neurological Complications After Endovascular Treatment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Procedure-related neurological complications are common after endovascular treatment of unruptured intracranial aneurysms. We aimed to develop a score to quantify individual patient risk. METHODS: We retrospectively analyzed consecutive patients who underwent endovascular treatment for unruptured intracranial aneurysms between January 2012 and September 2015. After excluding those who lost to follow-up and those with fusiform unruptured intracranial aneurysms, included patients were randomly divided into a derivation group (60%) and a validation group (40%). A neurological complication was defined as any transient or permanent increase in the modified Rankin Scale score after aneurysm embolization. A risk score for neurological complications was derived from multivariable logistic regression analyses in the derivation group and validated in the validation group. RESULTS: Overall, 1060 patients were included (636 in the derivation group and 424 in the validation group). The incidence of neurological complications was 5.5% (95% confidence interval, 3.8%-7.4%). A 3-point risk score (S-C-C) was derived to predict neurological complications (size [≥10 mm=1], core areas [yes=1], and cerebral ischemic comorbidity [yes=1]). The incidence of neurological complications varied from 2.2% in 0-point patients to 25.0% in 3-point patients. The score demonstrated significant discrimination (C-statistic, 0.714; 95% confidence interval, 0.624-0.804) and calibration (McFadden R(2), 0.102) in the derivation group. Excellent prediction, discrimination, and calibration properties were reproduced in the validation group. CONCLUSIONS: One in 20 patients will develop neurological complications after endovascular treatment of unruptured intracranial aneurysms. The S-C-C score may be useful for predicting these adverse outcomes based on variables in daily practice.

Is a highly pathogenic avian influenza virus H5N1 fragment recombined in PB1 the key for the epidemic of the novel AIV H7N9 in China, 2013?

BACKGROUND: A novel avian influenza A H7N9 virus that infects humans was identified in China in 2013. This study is the first to comprehensively investigate the characteristics of genomic recombination, rather than reassortment, which has been the subject of investigation in previously reported studies. METHODS: Novel avian influenza virus (AIV) H7N9 genome sequences were obtained from the NCBI Influenza Virus Sequence Database and the Global Initiative on Sharing Avian Influenza Database (GISAID) and a representative isolate was subjected to homogeneity analysis. A phylogenetic tree was constructed. Eight segments of the isolate were analyzed to identify segments with recombination events, the corresponding recombination fragments, and breakpoints. The evolutionary history of the recombined fragments was tracked by constructing phylogenetic trees of the recombination fragments. RESULTS: Among the eight segments of the novel AIV H7N9 analyzed, only the PB1 segment showed a marked recombination phenomenon, with 11 recombination events; these included five actual recombination events and six possible misalignment artifact recombination events. The most notable was the recombination of a 291-nucleotide (nt) fragment at the 490-780 nt site that was affiliated to a highly pathogenic avian influenza virus (HPAIV) H5N1 (A/tree sparrow/Thailand/VSMU-16-RBR/2005). The phylogenetic tree of the 291-nt recombination fragment on the PB1 segment showed that the novel AIV H7N9 had a close genetic relationship to H9N2 and H5N1. CONCLUSIONS: The novel AIV H7N9 might have reassorted its PB1 segment from H9N2 circulating in China, and this H9N2 PB1 might have been recombined into a highly pathogenic fragment from HPAIV H5N1, which could be the reason for the high fatality rate among patients with AIV H7N9 influenza.