BACKGROUND: Skull base malignancies are problematic. We evaluated the efficacy and toxicity of gamma knife radiosurgery (GKRS) in the treatment of patients with primary and secondary malignancies in the skull base. METHODS: The data of 43 patients were retrospectively analyzed. Sixteen of these patients had a primary skull base malignancy, and 27 patients had skull base metastasis or an invasion from other cancers. The median tumor volume was 7.2cm(3)(range, 0.6-33.4). The median prescription margin dose was 14.0Gy (range, 10-16). Nine patients with tumor regrowth after initial reduction received another treatment. RESULTS: The median follow-up time was 14 months (range, 1-60). Following GKRS, the progression-free survival was 89% and 62% at 1 and 2 years, respectively, and the overall survival rate was 74% and 45% at 1 and 2 years, respectively. Nineteen (44%) patients reported an improvement following GKRS. One patient (2%) reported decreased vision, which was considered to be a side effect from cumulative GKRS doses. CONCLUSION: Gamma knife radiosurgery is an effective treatment for primary and secondary malignant tumors in the skull base as initial monotherapy or as an adjunct therapy to surgery or radiotherapy.

Benzo(a)pyrene (BaP) never exists in the environment as a single compound but always coexists with other chemicals. These chemicals may affect the toxicity of BaP. Our previous study confirmed that polychlorinated biphenyls (PCBs), which were recently found coexisting with BaP in various environmental media, dramatically enhanced the genotoxicity of BaP. But the known mechanisms associated with this phenomenon are limited. Because BaP's genotoxicity is highly associated with its ability to induce the oxidative stress, we propose that the coexistence of PCBs may enhance BaP's genotoxicity by affecting BaP-induced oxidative stress. In this study, the HepG2 cells were treated with either BaP (50 μM), 3,3',4,4',5-pentachlorobiphenyl (PCB126)(0.01, 0.1, 1, and 10 nM), or pretreated with PCB126 followed by a coexposure to BaP and PCB126. We found that the exposure to BaP alone effectively increased the level of reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and the percentage of cells in G0/G1 phase, but decreased the percentage of S-phase cells. Compared to BaP alone, coexposure to both BaP and PCB126 effectively enhanced the levels of ROS and MDA as well as the percentage of cells in S phase, but decreased the levels of GSH and percentage of cells in G0/G1 phase. Our findings suggest that increasing oxidative stress and impairing the normal cell-cycle control may be mechanisms by which PCB126 enhances the genotoxity of BaP exposure. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.

OBJECTIVES. To determine current trends for different modes of delivery in twin pregnancies, factors affecting the mode of delivery, and associated outcomes. DESIGN. Retrospective cohort study. SETTING. A public hospital in Hong Kong. PARTICIPANTS. All twin pregnancies booked at Kwong Wah Hospital during a 3-year period from 1 April 2006 to 31 March 2009. RESULTS. Of 197 sets of twins, 35 (18%) were delivered vaginally and 162 (82%) by caesarean section (47% were emergencies and 53% elective). In all, 32 (37%) of the elective and 21 (28%) of the emergency caesarean sections were in response to maternal requests. Vaginal delivery was more common in mothers with a history of vaginal delivery and monochorionic diamniotic twins. Women who conceived by assisted reproduction or those who had a tertiary education were more likely to deliver by caesarean section. The type of conception and the presentation of the second twin were statistically significant factors affecting maternal choice on the mode of delivery. Maternal age did not affect the choice of delivery mode. Except for the higher frequency of sepsis and cord blood acidosis in second twins delivered vaginally, there were no significant differences in neonatal morbidity between the groups that attempted vaginal delivery or requested caesarean sections. All the women who had compression sutures or hysterectomy to control massive postpartum haemorrhage were delivered by caesarean section. CONCLUSION. A high caesarean section rate observed in our cohort was associated with maternal requests for this mode of delivery. The type of conception and the presentation of the second twin were statistically significant factors affecting maternal choice on mode of delivery. Women's requests for caesarean delivery out of the concern for their babies are not supported by current evidence. In response to a woman with a twin pregnancy requesting caesarean delivery, the pros and cons of vaginal deliveries and caesarean sections should be fully explained before the woman's autonomy is respected.

The origin of the peroxidase-like activity of gold nanoparticles and the impact of surface modification are studied. Furthermore, some influencing factors, such as fabrication process, redox property of the modifier, and charge property of the substrate, are investigated. Compared to amino-modified or citrate-capped gold nanoparticles, unmodified gold nanoparticles show significantly higher catalytic activity toward peroxidase substrates, that is, the superficial gold atoms are a contributing factor to the observed peroxidase-like activity. The different catalytic activities of amino-modified and citrate-capped gold nanoparticles toward 3,3',5,5'-tetramethylbenzidine (TMB) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) show that the charge characteristics of the nanoparticles and the substrate also play an important role in the catalytic reactions.

The mammalian target of rapamycin (mTOR) signaling pathway is upregulated in the pathogenesis of many cancers. Arachidonic acid (AA) and its metabolites play critical role in the development of breast cancer, but the mechanisms through which AA promotes mammary tumorigenesis and progression are poorly understood. We found that the levels of AA and cytosolic phospholipase A2 (cPLA2) strongly correlated with the signaling activity of mTORC1 and mTORC2 as well as the expression levels of vascular epithelial growth factor (VEGF) in human breast tumor tissues. In cultured breast cancer cells, AA effectively activated both mTOR complex 1 (mTORC1) and mTORC2. Interestingly, AA-stimulated mTORC1 activation was independent of amino acids, phosphatidylinositol 3-kinase (PI3-K) and tuberous sclerosis complex 2 (TSC2), which suggests a novel mechanism for mTORC1 activation. Further studies revealed that AA stimulated mTORC1 activity through destabilization of mTOR-raptor association in ras homolog enriched in brain (Rheb)-dependent mechanism. Moreover, we showed that AA-stimulated cell proliferation and angiogenesis required mTOR activity and that the effect of AA was mediated by lipoxygenase (LOX) but not cyclooxygenase-2 (COX-2). In animal models, AA-enhanced incidences of rat mammary tumorigenesis, tumor weights and angiogenesis were inhibited by rapamycin. Our findings suggest that AA is an effective intracellular stimulus of mTOR and that AA-activated mTOR plays critical roles in angiogenesis and tumorigenesis of breast cancer.Oncogene advance online publication, 20 February 2012; doi:10.1038/onc.2012.47.

A new lignan glycoside, 7α, 7'β-bis-(4-hydroxy-3-methoxyphenyl)-7,9':7',9-diepoxylignan-8αH,8'α-O-β-d-(2″,7'α-epoxy)-glucopyranoside, named elshrugulosain (1), has been isolated from the EtOH extract of Elsholtzia rugulosa, together with six known compounds,(-)-bornyl (E)-3,4,5-trimethoxycinnamate, apigenin, luteolin, apigenin-7-O-β-d-glucopyranoside, luteolin-7-O-β-d-glucopyranoside, and luteolin-3'-glucuronate methyl ester. Their structures were characterized by spectroscopic methods and comparison with the data in the literature. On the basis of detailed 1D and 2D NMR spectral analysis, as well as X-ray crystallographic diffraction, the NMR spectroscopic data of (-)-bornyl (E)-3,4,5-trimethoxycinnamate were revised and assigned completely.

Disinfection of drinking water reduces pathogenic infection, but generates disinfection by-products (DBPs) in drinking water. In this study, the effect of fifteen DBPs on DNA damage in human-derived hepatoma line (HepG2) was investigated by the single cell gel electrophoresis (SCGE) assay. These fifteen DBPs are: four trihalomethanes (THMs), six haloacetic acides (HAAs), three haloacetonitriles (HANs), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), and chloral hydrate (CH). Based on the minimal effective concentration (MEC) at which DBPs induced significant increase in olive tail moment (OTM), the rank order of DNA-damaging potency is: bromodichloromethane (BDCM)>dibromochloromethane (DBCM)>tribromomethane (TBM)>trichloromethane (TCM) of the four THMs; iodoacetic acid (IA)>bromoacetic acid (BA)>dibromoacetic acid (DBA)>dichloracetic acid (DCA)>trichloroacetic acid (TCA) of the five HAAs; dibromoacetonitrile (DBN)approximately dichloroacetonitrile (DCN)>trichloroacetonitrile (TCN) of the three HANs. The DNA damaging potency of MX and CH is similar to TCA and DCA, respectively. IA is the most genotoxic DBP in the fifteen DBPs, followed by BA. Chloroacetic acid (CA) is not genotoxic in this assay. Our findings indicated that HepG2/SCGE is a sensitive tool to evaluate the genotoxicity of DBPs and iodinated DBPs are more genotoxic than brominated DBPs, but chlorinated DBPs are less genotoxic than brominated DBPs.

The complete DNA sequence of Marek's disease virus (MDV) serotype 1 vaccine strain 814 was determined. It consisted of 172,541 bp, with an overall gene organization identical to that of the MDV-1 type strains. Comparative genomic analysis of vaccine strains (814 and CVI988) and other strains (CU-2, Md5, and Md11) showed that 814 was most similar to CVI988. Several unique insertions, deletions, and substitutions were identified in strain 814. Of note, a 177-bp insertion in the overlapping genes encoding the Meq, RLORF6, and 23-kDa proteins of strain 814 was identified, and a 69-bp deletion was also located in the origin of replication site (Ori) in the gene encoding RLORF12. Compared to the CVI988 vaccine strain, a deletion of 510 bp was identified in the UL36 gene. These analyses identified key mutations in the 814 strain and the vaccine strain that could be exploited for future MDV vaccine design.

Although several flavonoids have been reported to exert inhibitory effects on influenza H1N1 neuraminidase (NA), little is known about the structure-activity relationship and binding mode. Three dimensional QSAR (quantitative structure-activity relationship) and molecular docking approaches were applied to explore the structural requisites of flavone derivatives for NA inhibitory activity. A meaningful QSAR model with R(2) of 0.5968, Q(2) of 0.6457, and Pearson-R value of 0.8679, was constructed. From the QSAR model, it could be seen how 6-OH, 3'-OH, 4'-OH, and 8-position substituent affect the NA inhibitory activity. Molecular docking study between the most active compound and NA suggested that hydrogen bonds, hydrophobic and electrostatic interactions were closely related to NA inhibitory activity, 5-OH and 7-OH may be essential for this activity. The results provide a set of useful guidelines for the rational design of novel NA inhibitors.

Spontaneous rupture of an iliac vein is a very rare condition, with 34 reported cases in the previously published data and only two cases involving the right side. We report the third case of spontaneous rupture of the right external iliac vein. A 62-year-old woman presented with sudden onset of lower abdominal pain and an inability to move the right lower extremity shortly after stretching her right leg backward. A contrast computed tomography demonstrated a massive pelvic retroperitoneal hematoma and a thrombus extending from the inferior vena cava to the right iliac veins. An inferior vena cave filter was inserted using interventional radiology, followed by an exploratory laparotomy. A 1.5-cm laceration in the right external iliac vein was uncovered and repaired. The etiology, clinical features, and treatment of spontaneous iliac vein rupture are discussed.