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With the insertion a segment of polarization-maintaining fiber (PMF) inside the cavity, abundant dynamics of group velocity locked vector solitons (GVLVSs) in Er-doped fiber laser have been investigated by using graphene oxide/polyvinyl alcohol (GO/PVA) film as a saturable absorber (SA). The generated Kelly sidebands in emission spectra reveal peak-valley or valley-peak alternation and slightly shift in two orthogonal components, which are the characteristics of GVLVSs. Through proper adjustment of polarization controllers (PCs) inside the EDFLs cavity, versatile vector soliton dynamics such as polarization locked GVLVSs (PL-GVLVSs), polarization rotation GVLVSs (PR-GVLVSs), dual wavelength GVLVSs, bound state GVLVSs, bunch GVLVSs and harmonic mode-locking GVLVSs (HML-GVLVSs) have been observed. The separation between two emission peaks from the dual wavelength GVLVSs was controlled by the Lyot filter and related to the insertion length of PMF inside the cavity. Unlike PL-GVLVSs, the period-doubling phenomenon has been found in two orthogonal components of the PR-GVLVSs. Besides, the bound state GVLVSs were generated showing strongly modulated interference fringes in emission spectrum. For the bunch and HML GVLVSs, the number of solitons inside the cavity increased with the pump power, and it showed the quintuple solitons and the 7th HML-GVLVSs at the highest pump power. [ABSTRACT FROM AUTHOR]

An anionic three-dimensional framework {(Me2NH2)2[Zn8(L)6(ad)4(μ4-O)]·10DMF·11H2O}(Zn-MOF, L2− = 4,4′-(3-aminopyridine-2,5-diyl)dibenzoic acid; ad− = adeninate) with a column-layered structure was synthesized. Structural studies show that the Zn-MOF has octahedral cages [Zn8(ad)4(μ4-O)], the adjacent cages are connected by O atoms to form 1D columnar SBUs, and every four SBUs are connected by L2− to form a square channel 3D framework. Gas adsorption studies show that the BET and Langmuir surface areas of Zn-MOF are 1370.31 and 1478.04 m2 g−1, respectively, and the total pore volume for single-point adsorption is 0.528 cm3 g−1. The surface of the pores of the Zn-MOF is occupied by open metal sites and uncoordinated carboxyl groups, showing good capture ability for C2H2 and good adsorption selectivity for C2H2/CH4. More importantly, the free (CH3)2NH2+ ions present in the pores of the columnar layered Zn-MOF can cation-exchange with MB, MV, and RhB ions in aqueous solution. Therefore, Zn-MOF can not only effectively adsorb the cationic dyes MB, MV, and RhB, but also exhibit particularly selective sorption towards the mixed anion and cation dyes MB/MO and MV/MO. In addition, a series of fluorescence experiments show that Zn-MOF has good fluorescence properties, exhibiting highly selective and sensitive fluorescence detection and recognition performance for Fe3+ ions in aqueous solution with a low detection limit. [ABSTRACT FROM AUTHOR]

BACKGROUND: The knee plays an essential role in movement. There are four major ligaments in the knee which all have crucial functionalities for human activities. The anterior cruciate ligament (ACL) is the most commonly injured ligament in the knee, especially in athletes. OBJECTIVE: The aim of this study was to investigate the dynamic tensile response of the porcine ACL at strain rates from 800 to 1500 s−1 for simulations of acute injury from sudden impact or collision. METHODS: Split Hopkinson Tension Bar (SHTB) was utilized to create a dynamic tensile wave on the ACL. Stress–strain curves of strain rates between 800 s−1 to 1500 s−1 were recorded. RESULTS: The results demonstrated that the elastic modulus of the porcine ACL at higher strain rates was six to eight times higher than that of porcine and human specimens at quasi-static strain rate. However, the failure stress was quite similar while the strain was much smaller than that at the lower strain rate. CONCLUSIONS: ACL is highly strain rate sensitive and easier to break with lower failure strain when the strain rates increased to more than 1000 s−1. The stress–strain curves indicated that the sketching crimps at the slack region did not happen but switched to the sliding process of collagen fibers and was accompanied by some ruptures, which can develop into tears when strain and stress were large enough. On the other hand, the viscoelastic properties of the ligament, depending on the proteoglycan matrix and the cross-link, showed a limited value in the studied strain rate range. [ABSTRACT FROM AUTHOR]

Background: Exosomal long non-coding RNAs (lncRNAs) have been recognised as promising stable biomarkers in cancers. The aim of this study was to identify an exosomal lncRNA panel for diagnosis and prognosis of esophageal squamous cell carcinoma (ESCC). Materials and Methods: Exosomes were isolated from serum by ExoQuick Solution. To validate the exosomes, exosomal markers and characterization of nanoparticle were performed. Quantitative real-time PCR was used to measure the levels of lncRNAs in exosomes from ESCC patients and healthy subjects. In the training set, exosomal lncRNA profiles from 404 samples were conducted and established new models by multivariate logistic regression. In the validation set, the diagnostic performance of the panel was further validated in 222 additional individuals with a receiver operating characteristic curve (ROC). Kaplan–Meier and multivariate Cox proportional hazards analysis were applied to assess the correlation between lncRNAs and survival rate of ESCC patients. Results: A 4-lncRNA panel (UCA1, POU3F3, ESCCAL-1 and PEG10) in exosomes for ESCC diagnosis was developed by logistic regression model. The diagnostic accuracy of panel was evaluated with AUC value of 0.844 and 0.853 for training and validation stage, respectively. The corresponding AUCs for patients with TNM stage I–II and III were 0.820 and 0.935, significantly higher than squamous cell carcinoma antigen (P< 0.001), which were 0.652 and 0.642, respectively. Kaplan–Meier analysis indicated that patients with higher level of UCA1 and POU3F3 had lower survival rate (P< 0.001). Additionally, POU3F3 might be as an independent prognostic factor for ESCC patients (P=0.004). Conclusion: These findings suggested that serum exosomal 4-lncRNA panel has considerable value for ESCC diagnosis, and POU3F3 may serve as a novel and independent prognostic predictor in clinical applications. [ABSTRACT FROM AUTHOR]

Exosomes are small membrane vesicles released by many cells. These vesicles can mediate cellular communications by transmitting active molecules including long non‐coding RNAs (lncRNAs). In this study, our aim was to identify a panel of lncRNAs in serum exosomes for the diagnosis and recurrence prediction of bladder cancer (BC). The expressions of 11 candidate lncRNAs in exosome were investigated in training set (n = 200) and an independent validation set (n = 320) via quantitative real‐time PCR. A three‐lncRNA panel (PCAT‐1, UBC1 and SNHG16) was finally identified by multivariate logistic regression model to provide high diagnostic accuracy for BC with an area under the receiver‐operating characteristic curve (AUC) of 0.857 and 0.826 in training set and validation set, respectively, which was significantly higher than that of urine cytology. The corresponding AUCs of this panel for patients with Ta, T1 and T2‐T4 were 0.760, 0.827 and 0.878, respectively. In addition, Kaplan‐Meier analysis showed that non‐muscle‐invasive BC (NMIBC) patients with high UBC1 expression had significantly lower recurrence‐free survival (P = 0.01). Multivariate Cox analysis demonstrated that UBC1 was independently associated with tumour recurrence of NMIBC (P = 0.018). Our study suggested that lncRNAs in serum exosomes may serve as considerable diagnostic and prognostic biomarkers of BC. [ABSTRACT FROM AUTHOR]

To study the efficacy and safety of hematoma puncture catheter drainage under CT real-time guide for treatment of intracerebral hemorrhage (ICH). Methods A total of 80 ICH patients with hematoma volume 15-30 ml were given conservative treatment (control group, 40 cases including 6 cases with hematoma volume 15-20 ml and 34 cases with hematoma volume > 20-30 ml) and hematoma puncture and catheter drainage under CT real-time guide (operation group, 40 cases with hematoma volume > 20-30 ml). Conscious states were evaluated by Glasgow Coma Scale (GCS) on admission and 3 d after onset. Neurological deficits of patients were evaluated by National Institutes of Health Stroke Scale (NIHSS) on admission and discharge. Hospitalization days and complications (including rebleeding, epilepsy, intracranial infection, severe pulmonary infection and bleeding caused by digestive tract stress ulcer) were recorded. Results The GCS scores 3 d after onset (P = 0.000) and NIHSS scores on discharge (P = 0.000) of 2 groups were significantly lower than those on admission. The GCS score of operation group was significantly higher (P = 0.003) and NIHSS score was significantly lower (P = 0.000) than that of control group. The hospitalization time of operation group was significantly lower than those of control group [(10.53 ± 2.64) d vs. (17.30 ± 4.92) d; t = 7.673, P = 0.000]. Complications including rebleeding, intracranial infection, severe pulmonary infection and bleeding caused by digestive tract stress ulcer did not occur in patients of 2 groups. Conclusions For supratentorial hemorrhage patients with hematoma volume 15-30 ml, in comparison with conservative treatment, operation with hematoma puncture and catheter drainage under CT real-time guide can save hospitalization days, relieve edema peak response and improve the prognosis. [ABSTRACT FROM AUTHOR]

Background: Dabigatran etexilate is a prodrug whose absorption is opposed by intestinal P-glycoprotein and which is converted by carboxylesterase to its active form, dabigatran. Unlike other statins, simvastatin and lovastatin are potent inhibitors of P-glycoprotein and carboxylesterase, and might either increase the risk of hemorrhage with dabigatran etexilate or decrease its effectiveness.Methods: We conducted 2 population-based, nested case-control studies involving Ontario residents 66 years of age and older who started dabigatran etexilate between May 1, 2012, and Mar. 31, 2014. In the first study, cases were patients with ischemic stroke; in the second, cases were patients with major hemorrhage. Each case was matched with up to 4 controls by age and sex. All cases and controls received a single statin in the 60 days preceding the index date. We determined the association between each outcome and the use of simvastatin or lovastatin, relative to other statins.Results: Among 45 991 patients taking dabigatran etexilate, we identified 397 cases with ischemic stroke and 1117 cases with major hemorrhage. After multivariable adjustment, use of simvastatin or lovastatin was not associated with an increased risk of stroke (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.88 to 2.01). In contrast, use of simvastatin and lovastatin were associated with a higher risk of major hemorrhage (adjusted OR 1.46, 95% CI 1.17 to 1.82).Interpretation: In patients receiving dabigatran etexilate, simvastatin and lovastatin were associated with a higher risk of major hemorrhage relative to other statins. Preferential use of the other statins should be considered in these patients. [ABSTRACT FROM AUTHOR]

Background: Recently, several new atypical antipsychotic agents have been introduced in Ontario, and regulatory warnings have been issued regarding use of atypical antipsychotics in older adults. We sought to establish the impact of newer atypical antipsychotics on prescribing rates and costs. Methods: We performed a population-based cross-sectional study of Ontario adults aged 65 years or more using atypical antipsychotics from Jan. 1, 2007, to Mar. 31, 2013. These people have universal access to publicly funded drugs through the Ontario Health Insurance Plan and the Ontario Drug Benefit. We conducted time-series analysis to assess the impact of the introduction of new atypical antipsychotics on rates of use of atypical antipsychotics and associated expenditures. Results: Rates of atypical antipsychotic use increased following the introduction of new agents in 2009, from 27.6 users per 1000 older adults in the third quarter of 2009 to 29.1 users per 1000 older adults at the end of the study period (p = 0.04). Although prescribing rates for the newer atypical agents (paliperidone, ziprasidone and aripiprazole) remained low relative to their older counterparts (risperidone, olanzapine and quetiapine), rates of aripiprazole use rose to 1.0 user per 1000 older adults by the end of the study period. The proportion of prescriptions that were for brand-name agents fell from 57.5% in the second quarter of 2007 to 6.1% in the second quarter of 2009, and then rose to 11.7% by the end of the study period. By the first quarter of 2013, newer atypical antipsychotic agents were used by 4.4% of atypical antipsychotic users but accounted for 14.1% ($1.2 million of $8.5 million) of atypical antipsychotic expenditures. Interpretation: Although the overall prevalence of use of new atypical antipsychotic agents remains low, their introduction has led to increased prescribing of this class of drugs in older adults. Given the potential cost implications, further study of these trends would be prudent. [ABSTRACT FROM AUTHOR]

The effect of high-pressure treatment (0.1 to 500 MPa for 10 min) on the moisture sorption properties of brown rice(Feng Liang You Xiang No. 1) was investigated. Air was maintained at selected conditions (temperature between 20°C and 40°C, equilibrium relative humidity between 11% and 75%) and equilibrium moisture content was measured. The control attained a higher equilibrium moisture content than treated samples, while the 300 MPa treated sample had the lowest. The area of hysteresis of the 300 MPa test sample was the largest and the BET model was applied to determine the monolayer moisture content. [ABSTRACT FROM AUTHOR]

Effects of presoaking-high hydrostatic pressure (PHHP) on cooking time, hardness, gumminess, springiness, and microstructure of brown rice were evaluated. Compared with traditional soaking treatment, PHHP significantly shorten the cooking time of brown rice from 34 to 14 min. The hardness of brown rice treated by PHHP reduced remarkably, which is lower than that treated by soaking process and similar to that of white rice. The gumminess and springiness of brown rice dramatically decreased under pressure above 500 MPa. However, the water uptake capacity of brown rice treated by PHHP was not obviously affected, whose moisture contents were much lower than that of soaked samples. The analysis of thermal properties revealed that the enthalpy of brown rice was influenced by PHHP, and the denaturation of brown rice components generated. These results and microstructure analysis revealed that the structures of pericarp and aleurone layer of brown rice were damaged by PHHP, which allows water to be easily absorbed by the rice kernel during cooking process. PHHP treatment could be a potentially applicable pretreatment for improving cooking properties of brown rice. [ABSTRACT FROM AUTHOR]

Histone, and non-histone, protein acetylation plays an important role in a variety of cellular events, including the normal and abnormal development of blood cells, by changing the epigenetic status of chromatin and regulating non-histone protein function. Histone acetyltransferases (HATs), which are the enzymes responsible for histone and non-histone protein acetylation, contain p300/CBP, MYST, and GNAT family members. HATs are not only protein modifiers and epigenetic factors but also critical regulators of cell development and carcinogenesis. Here, we will review the function of HATs such as p300/CBP, Tip60, MOZ/MORF, and GCN5/PCAF in normal hematopoiesis and the pathogenesis of hematological malignancies. The inhibitors that have been developed to target HATs will also be reviewed here. Understanding the roles of HATs in normal/malignant hematopoiesis will provide the potential therapeutic targets for the hematological malignancies. [ABSTRACT FROM AUTHOR]

Background: The incidence of neonatal opioid withdrawal is increasing in both Canada and the United States. However, the degree to which the treatment of pain with opioids, rather than the misuse of prescription opioids or heroin, contributes to the prevalence of neonatal opioid withdrawal remains unknown. Methods: We conducted a retrospective, population-based, cross-sectional study between 1992 and 2011 in Ontario with 2 objectives. First, we determined the annual incidence of neonatal abstinence syndrome. Second, using data from a subset of women eligible for publicly funded prescription drugs, we determined what proportion of women who deliver an infant with neonatal abstinence syndrome were given a prescription for an opioid before and during pregnancy. Results: The incidence of neonatal abstinence syndrome in Ontario increased 15-fold during the study period, from 0.28 per 1000 live births in 1992 to 4.29 per 1000 live births in 2011. During the final 5 years of the study, we identified 927 deliveries of infants with neonatal abstinence syndrome to mothers who were public drug plan beneficiaries. Of these mothers, 67% had received an opioid prescription in the 100 days preceding delivery, including 53.3% who received methadone, an increase from 28.6% in the interval spanning 1 to 2 years before delivery (p < 0.001). Prescription for nonmethadone opioids decreased from 38% to 17% (p < 0.001). Interpretation: The incidence of neonatal opioid withdrawal in Ontario has increased substantially over the last 20 years. Most of the women in this cohort who delivered an infant with neonatal abstinence syndrome had received a prescription for an opioid both before and during their pregnancy. [ABSTRACT FROM AUTHOR]

Background: The increased use of opioid analgesics, sedative hypnotics and stimulants, coupled with the associated risks of overdose have raised concerns around the inappropriate prescribing of these monitored drugs. We assessed the impact of new legislation, the Narcotics Safety and Awareness Act, and a centralized Narcotics Monitoring System (implemented November 2011 and May 2012, respectively), on the dispensing of prescriptions suggestive of misuse. Methods: We conducted a time series analysis of publicly funded prescriptions for opioids, benzodiazepines and stimulants dispensed monthly in Ontario from January 2007 to May 2013, based on information in the Ontario Public Drug Benefit Database. In the primary analysis, a prescription was deemed potentially inappropriate if it was dispensed within 7 days of an earlier prescription and was for at least 30 tablets of a drug in the same class as the earlier prescription, but originated from a different physician and a different pharmacy. Results: After enactment of the new legislation, the prevalence of potentially inappropriate opioid prescriptions decreased by 12.5% in 6 months (from 1.6% in October 2011 to 1.4% in April 2012; p = 0.01). No further significant change was observed after the introduction of the narcotic monitoring system (p = 0.8). By May 2013, the prevalence had dropped to 1.0%. Inappropriate benzodiazepine prescribing was significantly influenced by both the legislation (p < 0.001) and the monitoring system (p = 0.05), which together reduced potentially inappropriate prescribing by 50.0% between October 2011 and May 2013 (from 0.4% to 0.2%). The prevalence of potentially inappropriate prescribing of stimulants was significantly influenced by the introduction of the monitoring system in May 2012, falling from 0.7% in April 2012 to 0.3% in May 2013 (p = 0.02). Interpretation: For a select group of drugs prone to misuse and diversion, legislation and a prescription monitoring program reduced the prevalence of prescriptions suggestive of misuse. This suggests that regulatory interventions can promote appropriate prescribing which could potentially be applied to other jurisdictions and drugs of concern. [ABSTRACT FROM AUTHOR]

Background: Telmisartan, unlike other angiotensin -receptor blockers, is a partial agonist of peroxisome proliferator--activated receptor-γ, a property that has been associated with improvements in surrogate markers of cardiovascular health in small trials involving patients with diabetes. However, whether this property translates into a reduced risk of car- diovascular events and death in these patients is unknown. We sought to explore the risk of myocardial infarction, stroke and heart failure in patients with diabetes who were taking telmisartan relative to the risk of these events occurring in patients taking other angiotensin- receptor blockers. Methods: We conducted a population- based, retrospective cohort study of Ontario residents with diabetes aged 66 years and older who started treatment with candesartan, irbesartan, losartan, telmisartan or valsartan between Apr. 1, 2001, and Mar. 31, 2011. Our primary outcome was a composite of admission to hospital for acute myocardial infarction, stroke or heart failure. We examined each outcome individually in secondary analyses, in addition to all-cause mortality. Results: We identified 54 186 patients with diabetes who started taking an angiotensin- receptor blocker during the study period. After multivariable adjustment, patients who took either telmisartan (adjusted hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.74-0.97) or valsartan (adjusted HR 0.86, 95% CI 0.77-0.95) had a lower risk of the composite outcome compared with patients who took irbesartan. In contrast, no significant difference in risk was seen between other angiotensin-receptor blockers and irbesartan. In secondary analyses, we found a reduced risk of admission to hospital for heart failure with telmisartan compared with irbesartan (adjusted HR 0.79, 95% CI 0.66-0.96), but no significant differences in risk were seen between angiotensin-receptor blockers in our other secondary analyses. Interpretation: Compared with other angiotensin-receptor blockers, telmisartan and valsartan were both associated with a lower risk of admission to hospital for acute myocardial infarction, stroke or heart failure among older adults with diabetes and hypertension. Telmisartan and val sartan may there- fore be the preferred angiotensin-receptor blockers for use in these patients. [ABSTRACT FROM AUTHOR]

Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent due to its selective cytotoxicity to transformed cells. However, most human hepatocellular carcinomas (HCC) develop resistance to TRAIL. Thus, there is an urgent need to investigate the molecular targets and the underlying mechanisms that may be involved in overriding the resistance of tumor cells to TRAIL. Methods: Cell viability analysis was performed in HCC cells after treatment with TRAIL and/or ABT-263. Flow cytometry was used to assess apoptosis. The expression of caspases and members of the Bcl-2 family was examined through immunoblot analysis. Finally, the viability of cancer cells transfected with a plasmid containing HBx (hepatitis B virus X protein) following treatment with TRAIL was also measured. Results: In this study, we demonstrate that ABT-263, a potent and orally bioavailable inhibitor of the Bcl-2 family, was able to reverse the resistance of hepatocarcinoma cell lines to TRAIL-induced apoptosis, while sparing normal liver cells. The molecular mechanism of the reversal in resistance may be attributed to the inhibition by ABT-263 of anti-apoptosis proteins of the Bcl-2 family. In addition, we determined that HBx was able to sensitize TRAIL-resistant hepatocarcinoma Huh7 cells. Conclusions: These findings provide a novel insight into the clinical application of TRAIL-induced apoptosis of HCC cells. [ABSTRACT FROM AUTHOR]

The epidermal growth-factor receptor (EGFR) tyrosine kinase inhibitor erlotinib has been proven to be highly effective in the treatment of nonsmall cell lung cancer (NSCLC) harboring oncogenic EGFR mutations. The majority of patients, however, will eventually develop resistance and succumb to the disease. Recent studies have identified secondary mutations in the EGFR (EGFR T790M) and amplification of the N-Methyl-N'-nitro-N-nitroso-guanidine (MNNG) HOS transforming gene (MET) oncogene as two principal mechanisms of acquired resistance. Although they can account for approximately 50% of acquired resistance cases together, in the remaining 50%, the mechanism remains unknown. In NSCLC-derived cell lines and early-stage tumors before erlotinib treatment, we have uncovered the existence of a subpopulation of cells that are intrinsically resistant to erlotinib and display features suggestive of epithelial-to-mesenchymal transition (EMT). We showed that activation of TGF-β-mediated signaling was sufficient to induce these phenotypes. In particular, we determined that an increased TGF-β-dependent IL-6 secretion unleashed previously addicted lung tumor cells from their EGFR dependency. Because IL-6 and TGF-β are prominently produced during inflammatory response, we used a mouse model system to determine whether inflammation might impair erlotinib sensitivity. Indeed, induction of inflammation not only stimulated IL-6 secretion but was sufficient to decrease the tumor response to erlotinib. Our data, thus, argue that both tumor cell-autonomous mechanisms and/or activation of the tumor microenvironment could contribute to primary and acquired erlotinib resistance, and as such, treatments based on EGFR inhibition may not be sufficient for the effective treatment of lung-cancer patients harboring mutant EGFR. [ABSTRACT FROM AUTHOR]

The article presents a study that developed and examined nonfluorinated copolymerized polyimide (PI) thin films with ultralow dielectric constants. The researchers used Fourier transform infrared and nuclear magnetic resonance (NMR) spectroscopy, thermogravimetric analysis and dynamic mechanical analysis to measure the structures and properties of the thin films. They found that excellent solubility was showed by all of the PI films in organic solvents.

Although the recently identified Pirh2 protein is known as a p53-induced ubiquitin-protein E3 ligase, which negatively regulates p53, the detailed mechanism underlying the regulation of Pirh2 remains largely unknown. Here, we demonstrate that while Pirh2 is mostly detected in the phosphorylated form in normal tissues, it is predominantly present in the unphosphorylated form in majority of tumor cell lines and tissues examined. Phosphorylated Pirh2 is far more unstable than its unphosphorylated form. We further identified that Calmodulin-dependent kinase II (CaMK II) phosphorylates Pirh2 on residues Thr-154 and Ser-155. Phosphorylation of Pirh2 appears to be regulated through cell cycle-dependent mechanism. CaMK II-mediated Pirh2 phosphorylation abrogates its E3 ligase activity toward p53. Together, our data suggest that phosphorylation of Pirh2 may act as a fine-tuning to maintain the balance of p53-Pirh2 autoregulatory feedback loop, which facilitates the tight regulation of p53 stability and tumor suppression. [ABSTRACT FROM AUTHOR]

Activation of the apical caspase-8 is crucial to the extrinsic apoptotic pathway. Although the death effector domain (DED) of caspase-8 has been reported to be involved in death-inducing signaling complex formation, the detailed mechanism of how DED functions in regulating apoptosis remains largely unknown. Here, we demonstrate that the prodomain of the caspase-8/Mch5 can be further cleaved between two tandemly repeated DEDs (DEDa–DEDb) at the amino-acid residue Asp129 by caspase-8 itself. The DEDa fragment generated from the endogenous caspase-8 was detected in isolated nucleoli upon treatment with TRAIL (tumor necrosis factor-related apoptosis-inducing ligand). Cleaved DEDa appears to translocate into the nucleus by association with extracellular signal-regulated protein kinases-1/2 (ERK1/2). Elimination of ERK1/2 expression by RNA interference resulted in a significant attenuation of nuclear entry of DEDa and reduced caspase-8-dependent apoptosis. In the nucleus, DEDa interacts with TOPORS, a p53 and topoisomerase I binding protein, and possibly displaces p53 from TOPORS, allowing p53 to stimulate caspase-8 gene expression. In summary, we postulate a positive feedback loop involving DEDa, which enables the continual replenishment of procaspase-8 during apoptosis. [ABSTRACT FROM AUTHOR]

Abstract Background. The aim of this study was to investigate the safety and efficacy of a heparin drug delivery system (HEP DDS) for prevention of posterior capsular opacification (PCO) in rabbits. Methods. Fifty New Zealand albino rabbits (50 eyes) undergoing phacoemulsification were equally divided into five groups receiving normal saline eye drops (group A), a carrier DDS implanted into the posterior chamber (group B), 5% heparin eye drops (group C), a HEP DDS implanted subconjunctivally (group D) and a HEP DDS implanted into the posterior chamber (group E). All the 50 eyes were examined by slit-lamp microscopy. The heparin levels in blood and aqueous humor were measured, and the wet posterior capsules were weighed. Results. All eyes in groups A and B had PCO at 5-7 days, much earlier than in groups C, D and E. Two eyes in group C, three eyes in group D and six eyes in group E showed no signs of PCO throughout the 12-week study. The mean weight of wet posterior capsules from groups A-E was 157.919 mg, 160.091 mg, 81.114 mg, 71.827 mg and 19.984 mg respectively. The mean aqueous humor heparin level in groups C, D and E was 10.279 μg/ml, 13.246 μg/ml and 25.964 μg/ml respectively. Cell proliferation of the posterior capsules in group E was not active. The conjunctiva, cornea, iris, ciliary body and retina remained intact, and no significant toxic reactions were observed. No intraocular hemorrhage occurred during the follow-up. Conclusion. Implantation of a HEP DDS into the posterior chamber of experimental animals significantly maintained a higher heparin level in aqueous humor for a relatively long period of time. The findings indicate potential prevention of PCO with minimum toxic and side effects. [ABSTRACT FROM AUTHOR]

The complete mitochondrial (mt) genome of the Neptune whelk,Neptunea arthritica cumingii, was determined using genome walking techniques in this study. The total length of the mt genome sequence ofN. arthritica cumingiiwas 15 256 bp, including 13 protein-coding genes, 21 transfer RNA genes and 2 ribosomal RNA genes. The overall composition of the mitogenome was estimated to be 30.85% for A, 38.59% for T, 15.15% for C and 15.40% for G, indicating that an A + T (69.44%)-rich feature occurs in theN. arthritica cumingiimitogenome. The phylogenetic relationships of 11 mollusc species were constructed based on the complete mtDNA sequences by the neighbour-joining method using MEGA 5.0 software (MEGA Inc., Englewood, NJ). [ABSTRACT FROM PUBLISHER]

Recently, expression signatures of exosomal long non-coding RNAs (lncRNAs) have been proposed as potential non-invasive biomarkers for cancer detection. In this study, we aimed to develop a urinary exosome (UE)-derived lncRNA panel for diagnosis and recurrence prediction of bladder cancer (BC). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to screen and evaluate the expressions of eight candidate lncRNAs in a training set (208 urine samples) and a validation set (160 urine samples). A panel consisting of three differently expressed lncRNAs (MALAT1, PCAT-1 and SPRY4-IT1) was established for BC diagnosis in the training set, showing an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.854. Subsequently, the performance of the panel was further verified with an AUC of 0.813 in the validation set, which was significantly higher than that of urine cytology (0.619). In addition, Kaplan-Meier analysis suggested that the up-regulation of PCAT-1 and MALAT1 was associated with poor recurrence-free survival (RFS) of non-muscle-invasive BC (NMIBC) (p < 0.001 and p = 0.002, respectively), and multivariate Cox proportional hazards regression analysis revealed that exosomal PCAT-1 overexpression was an independent prognostic factor for the RFS of NMIBC (p = 0.018). Collectively, our findings indicated that UE-derived lncRNAs possessed considerable clinical value in the diagnosis and prognosis of BC. [ABSTRACT FROM AUTHOR]

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An image that shows the association between statin use and ischemic stroke or major hemorrhage in patients who take dabigatran for atrial fibrillation is presented.

The article presents a nested case-control study on the impact of Trimethoprim-sulfamethoxazole and spironolactone drugs in the occurence of hyperkalaemia in older patients in Ontario. Multivariable conditional logistic regression analysis is used to study the influence of the said drugs. Findings reveal that approximately 60 % of hyperkalaemia in older patients who take spironolactone and treated with urinary tract infection antibiotics can be avoided without trimethoprim-sulfamethoxazole.

: BACKGROUND Embryo transfer is a crucial step in the IVF process. Most randomized prospective studies comparing transfer catheters have demonstrated significantly higher pregnancy rates with soft versus firm catheters, but none have taken the operator effect into account. Our aim was to perform a prospective randomized clinical trial comparing two catheters and to study interactions between catheters and operators. : METHODS A prospective randomized trial comparing the Cook K-SOFT-5100 and Frydman classical catheters 4.5 was performed. Three experienced operators participated in the trial, using a fixed distance transfer protocol. Primary end-point was clinical pregnancy rate, secondary end-points were rates of difficult transfer and of catheter failure. Patients were randomized by a computer program prior to embryo transfer. : RESULTS A total of 1446 embryo transfers were performed in 1155 women undergoing IVF or ICSI treatment. A total of 723 cycles were randomized to the Cook catheter and 723 cycles to the Frydman catheter. Following intention-to-treat analysis, the adjusted odds ratio of clinical pregnancy between for the Cook versus the Frydman catheter was 1.11 [95% confidence interval (95% CI) 0.89–1.38]. Odds ratios of clinical pregnancy between the Cook and Frydman catheters for the three operators were respectively 1.19 (95% CI 0.84–1.69), 2.35 (95% CI 1.40–3.95) and 0.69 (95% CI 0.48–0.99). : CONCLUSIONS Variation in pregnancy rates between embryo transfer catheters depends on variation between operators. Results from randomized clinical trials comparing embryo transfer catheters should not be generalized, because inconsistent conclusions may be unavoidable on the account of different proportions of cycles with transfers by each type of operator.The study was registered at clinicaltrials.gov. NCT00766714. [ABSTRACT FROM AUTHOR]

BACKGROUND We postulated that impaired endometrial differentiation in women with pelvic endometriosis predisposes for pre-eclampsia. METHODS A retrospective case–control study set at the University of Ghent IVF centre. The incidence of pre-eclampsia and pregnancy-induced hypertension (PIH) following the clinical and/or laparoscopic diagnosis of endometriosis-associated infertility (case group; n = 245 pregnancies) was compared with the incidence of these obstetric complications in pregnancies following treatment for male-factor infertility (control group; n = 274 pregnancies). Pregnancy data were obtained by searching electronic databases and postal questionnaires. The case and control groups were matched for age, parity and multiple pregnancies. RESULTS The incidence of pre-eclampsia was significantly lower in the case group (0.8%) when compared with control group (5.8%) (P = 0.002; odds ratio (OR) = 7.5, 95% confidence interval (CI): 1.7–33.3). Analysis of obstetric outcome in the subgroup of patients with laparoscopic data confirmed the lower risk of pre-eclampsia in the case (1.2%) versus control (7.4%) groups (P = 0.032; OR = 6.6, 95% CI: 1.2–37). PIH occurred in 3.5% and 8.7% of case and control pregnancies, respectively (P = 0.018; OR = 2.6, 95% CI: 1.2–6.0). The odds of developing pre-eclampsia were 5.67 times higher in the control group than in pregnancies following endometriosis-associated infertility. In multiple pregnancies, the odds of developing pre-eclampsia increased 1.93 times per additional child, with or without endometriosis. CONCLUSIONS We found no evidence that endometriosis predisposes for pre-eclampsia. Instead, the risk of hypertensive disorder in pregnancy is significantly reduced in women with endometriosis-associated infertility. [ABSTRACT FROM AUTHOR]