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Abstract: The cytokine interleukin-8 (IL-8) may play a role in the pathogenesis of nasopharyngeal carcinoma (NPC) through the modulation of tumor immune response or enhanced angiogenesis. Polymorphism of IL-8 gene, which may affect the production level of cytokine, has been inversely associated with a number of cancers. To test this hypothesis, we investigated the relationship of IL-8 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL-8 gene −845 T/C, −738 T/A, −353 A/T, −251 A/T and +678 T/C in 280 patients with NPC and 290 age and sex matched controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-sequence specific primers method (PCR-SSP). There were significant differences in the genotype and allele distribution of −251 A/T polymorphism of the IL-8 gene among cases and controls. The −251 AA and AT genotypes were associated with a significantly increased risk of NPC as compared with the −251 TT genotypes (OR=1.820, 95% CI, 1.120–2.959, P =0.015 and OR=1.590, 95% CI, 1.104–2.290, P =0.013, respectively). Haplotype analysis revealed that the homozygosity of the AAT haplotype (defined by SNPs at positions −353, −251 and +678) of IL-8 gene conveys the highest risk for NPC compared with the homozygosity for the TTC haplotype (OR=1.396; 95% CI, 1.064–1.831; P =0.016). The −251 A/T polymorphism of IL-8 and its haplotype are associated with NPC in a Chinese population. Our data suggests that IL-8 gene may play a role in the development of NPC. [Copyright &y& Elsevier]

Objective A recent randomized trial demonstrated that concurrent chemoradiotherapy (CCRT) with weekly cisplatin and gemcitabine, followed by two adjuvant cycles of cisplatin and gemcitabine improved survival for advanced cervical cancer patients. An Asian Gynecologic Oncology Group (AGOG) study was designed to determine whether only adding gemcitabine in the chemoradiation phase without adjuvant chemotherapy could improve survival. Methods Between March 2009 and March 2013, 74 eligible patients with International Federation of Obstetrics and Gynecology stage III/IVA cervical cancer or stage I/II with positive pelvic/para-aortic nodal metastasis were enrolled. Thirty-seven patients were randomized to arm C (weekly cisplatin 40 mg/m²) and 37 patients were randomized to arm CG (weekly cisplatin 40 mg/m² and gemcitabine 125 mg/m²), for six cycles. Six eligible patients were excluded before the beginning of treatment. Results An interim analysis showed superimposable progression-free (PFS) and overall survival (OS), a decision of closing accrual was made. A 3-year PFS was similar in both arms (arm C 65.1% vs. arm CG 71.0%, p = 0.71), and a 3-year OS was 74.1% in arm C vs. 85.9% in arm CG (p = 0.89), but crossed over at 5 years. Grade 2-4 hematological toxicities, including neutropenia (p = 0.028) and thrombocytopenia (p = 0.001), were more frequent in arm CG than arm C. Conclusions Despite limitation in power, it suggests that only adding gemcitabine at the CCRT phase does not provide substantially superior results, but treatment toxicities could increase. Further studies are required to determine the role of post-CCRT adjuvant chemotherapy in advanced cervical cancer. [ABSTRACT FROM AUTHOR]

• Fibrinogen, WBC, and neutrophils can predict CP-PSDS. • Fibrinogen, WBC, and neutrophils partially mediated stroke severity and CP-PSDS. • Fibrinogen and neutrophils play a chain mediating role in CP-PSDS. Post-stroke depression (PSD) is the most common psychological consequence of stroke. Increased inflammatory markers resulting from ischemic stroke may played an important role in the pathogenesis of depressive symptomology. The present study was conducted to further elucidate the relationship between stroke severity, systemic low-grade inflammation and chronic phase post-stroke depressive symptomology (CP-PSDS). A total of 897 stroke patients were consecutively recruited in this multicenter prospective cohort study and followed up for 1 year. The analytical sample consisted of 436 patients with ischemic stroke (23.4% female, median age = 57 years) from this cohort. Serum concentrations of inflammatory markers were measured in all 436 patients with ischemic stroke, from fasting morning venous blood samples on admission. Stroke severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) on admission and post-stroke depressive symptomology (PSDS) was evaluated by 17-item Hamilton Rating Scale for Depression (HRSD). In the fully adjusted models, we observed that 1) NIHSS (Model 2: β = 0.200, 95%CI, 0.057 ∼ 0.332), fibrinogen (Model 2: β = 0.828, 95%CI, 0.269 ∼ 1.435), white blood cell counts (WBC, model 2: β = 0.354, 95%CI, 0.122 ∼ 0.577) and neutrophil counts (Model 2: β = 0.401, 95%CI, 0.126 ∼ 0.655) can independently predict the CP-PSDS after ischemic stroke onset; 2) fibrinogen (Indirect effect = 0.027, 95%CI, 0.007 ∼ 0.063, 13.4% mediated), WBC (Indirect effect = 0.024, 95%CI, 0.005 ∼ 0.058, 11.8% mediated) and neutrophil counts (Indirect effect = 0.030, 95%CI, 0.006 ∼ 0.069, 14.8% mediated) could partially mediate the association between stroke severity and CP-PSDS, and 3) stroke severity might cause CP-PSDS partly through the chain-mediating role of both fibrinogen and neutrophil counts (chain mediated effect = 0.003, 95%CI, 0.000 ∼ 0.011, p = 0.025, 1.6% mediated). Findings revealed that fibrinogen, WBC and neutrophil counts may be independent predictors of CP-PSDS and partial mediators of the relationship between stroke severity and CP-PSDS among patients with ischemic stroke. In addition, the chain mediating effect of fibrinogen and neutrophil counts might play an important role in the occurrence of CP-PSDS. However, no inflammatory markers were associated with CP-PSDS in females. [ABSTRACT FROM AUTHOR]

Abstract: Cynomolgus monkeys are an important and widely used species in preclinical toxicology studies. During the in-life phase of study, body weight effects may be indicative of toxicity; however, trends in body weight and body weight variability are often difficult to interpret due to small sample size and/or inter- and intra-animal variability. The present analysis utilizes mixed-effect modelling, which incorporates random and fixed effects into linear regression models, to evaluate control monkey body weight trends and variability relative to baseline (initial) weight and study duration. The primary aim of this analysis is to evaluate whether mixed-effect model based tolerance limits can aide in determining whether apparent test article-related changes in body weight deviate more than the predicted variability defined by the model tolerance limits. The models for this study are based on vehicle control animal body weight data from the following studies: 1-month (20 studies, 198 animals), 3-month (19 studies, 180 animals), and 9-month (17 studies, 182 animals). The analysis presented herein provides the framework for evaluating control monkey body weight change in studies with small sample size, and anticipated control monkey body weight change relative to gender and study duration. [Copyright &y& Elsevier]

This multi-center international study (Asian Gynecologic Oncology Group [AGOG]13-001/Taiwanese Gynecologic Oncology Group [TGOG]1006) was to validate human papillomavirus (HPV)16 as an independent prognostic factor of cervical adenocarcinoma and adenosquamous carcinoma (AD/ASC). Retrospective and prospective collection of patients receiving primary treatment at AGOG and TGOG member hospitals for cervical AD/ASC were enrolled. The cases treated between 1993 and 2014 were retrospectively collected, and the prospective enrollment was started since 2014. Those endometrial origin (by immunohistochemistry and imaging studies) cannot rule out were excluded for analysis. A total of 354 patients were enrolled, 287 (81.1%) of which had HPV-positive tumors. The top-3 types among HPV-positive cases was HPV 18 (50.8%), HPV16 (22.9%) and HPV45 (4.0%). A total of 322 patients were eligible for prognostic analyses. Patient with HPV16-positivity had significantly longer progression-free survival (PFS) and overall survivals (OS) than those without HPV16 (p=0.001 and 0.026, respectively). By multivariate analysis, advanced FIGO stage (HR5.7, 2.4-13.5), lymph node metastasis (HR4.6, 2.7-7.9), tumor size (>4 cm HR3.3), and HPV16-positivity (HR0.3, 0.1-0.7) were independent prognostic factors for PFS. Only the former 2 variables remained significant, while HPV16-positivity was marginally significant (p=0.064) for OS. HPV-negativity rates varied across hospitals, yet it seemed to be increasing over time (4.4% versus 12.5%, p<0.001) in the hospital with largest sample size. This study confirmed that HPV16-positivity was a good prognostic factor for PFS, yet the increasing HPV-negative AD/ASCs seemed to be a trend that needs attention. [ABSTRACT FROM AUTHOR]

As emerging contaminants, antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have been widely detected in various aqueous environments. For antibiotic resistance to be inhibited in the environment, it is essential to control ARB and ARGs. In this study, dielectric barrier discharge (DBD) plasma was used to inactivate antibiotic resistant Escherichia coli (AR E. coli) and remove ARGs simultaneously. Within 15 s of plasma treatment, 108 CFU/mL of AR E. coli were inactivated by 97.9%. The rupture of the bacterial cell membrane and the increase of intracellular ROS are the main reasons for the rapid inactivation of bacteria. Intracellular ARGs (i- qnrB , i- blaCTX-M , i- sul2) and integron gene (i- int1) decreased by 2.01, 1.84, 2.40, and 2.73 log after 15 min of plasma treatment, respectively. In the first 5 min of discharge, extracellular ARGs (e- qnrB , e- blaCTX-M , e- sul2) and integron gene (e- int1) decreased by 1.99, 2.22, 2.66, and 2.80 log, respectively. The results of the ESR and quenching experiments demonstrated that ·OH and 1O 2 played important roles in the removal of ARGs. This study shows that DBD plasma is an effective technique to control ARB and ARGs in waters. • DBD plasma exhibited good performance in removing AR E. coli and its ARGs. • The degradation efficiency of iARGs is slower than that of eARGs. • OH and 1O 2 played important roles in the removal of ARGs. • Long-lived reactive species can help remove ARGs, especially extracellular ARGs. [ABSTRACT FROM AUTHOR]

Various shellfish samples were collected from seven coastal areas of Fujian, China, and their arsenic species characteristics were investigated. The results showed that there are six different arsenic species, i.e. arsenite, arsenate, dimethylarsinic acid, arsenobetaine, 5-deoxy-5-dimethylarsinoyl-β-ribofuranose and one unknown arsenic compound As1, existing in shellfish. Among 40 samples, arsenite was detected in 18 shellfish samples at the concentration range of 5–41 ng/g wet weight, and the later five arsenic species were detected in all shellfish samples at the concentration range of 0.01–0.07, 0.01–0.12, 0.13–1.52, 0.03–0.48 and 0.01–0.23 μg/g wet weight, respectively. The experimental results also revealed that the arsenic species characteristics in shellfish were dependent on both the shellfish species and sampling sites. For all 40 shellfish samples, arsenobetaine was the predominant species, its concentration accounted for 25–86% of total concentration of arsenic species; 5-deoxy-5-dimethylarsinoyl-β-ribofuranose was the subdominant arsenic species, its concentration accounted for 4–46% of total concentration of arsenic species. Our results provided basis for scientifically evaluating the arsenic uptake risk of shellfish samples. [ABSTRACT FROM AUTHOR]

Interleukin (IL) 13 plays a critical role in inflammatory diseases, including systemic lupus erythematosus (SLE). This study aims to explore the potential association of IL-13 polymorphisms with the risk of SLE. We genotyped IL-13 rs20541, rs848 and rs1295686 using Snapshot SNP genotyping assays. Plasma IL-13 level was determined by enzyme-linked immunosorbent assay (ELISA). We found that rs20541 was associated with increased risk of SLE (CT vs. CC: adjusted OR = 1.43, 95%CI, 1.04–1.99, P = .030; TT vs. CC: adjusted OR = 1.73, 95%CI, 1.10–2.73, P = .018; CT/TT vs. CC: adjusted OR = 1.50, 95%CI, 1.10–2.04, P = .010; T vs. C adjusted OR = 1.34, 95%CI, 1.08–1.93, P = .031). CT and TT genotypes in rs20541 were associated with increased risk of renal disorder in SLE (CT vs. CC: adjusted OR = 1.97, 95%CI, 1.18–3.28, P = .009; TT vs. CC: adjusted OR=2.42, 95%CI, 1.22–4.77, P = .011). Moreover, The concentration of IL-13 was significantly elevated in rs20541 CT/TT genotypes compared with CC genotype ( P < .001). These results suggest that rs20541 CT/TT genotypes may be a risk factor for SLE, probably by increasing the level of IL-13. [ABSTRACT FROM AUTHOR]

Objectives: α7-Human papillomavirus (HPV)-related cervical squamous cell carcinoma (SCC) treated with radiotherapy, or concurrent chemoradiation (RT/CCRT) is associated with poor prognosis. We aimed to discover the underlying relevant biomarkers. Methods: We compared the genomic profiles of α7-HPV-related cervical SCC (2001-2014 cohort) with different responses to radiotherapy or concurrent chemoradiation by microRNA profiling (miR4.0 array) and human transcriptome array 2.0, then verified by a real-time reverse-transcriptase quantitative polymerase chain reaction in order to discover predictive biomarkers. Results: We found significantly lower expression of miR143-3p in tumors with treatment failure (p = 0.0309), while one of the miR143-3p targets baculoviral inhibitor of apoptosis protein (IAP) repeat-containing 2 (BIRC2) mRNA expression (p = 0.0261) and BIRC2 protein levels (p = 0.0023) were significantly higher than those without treatment failure. Moreover, we showed that miR-143-3p sensitizes chemotherapy via targeting BIRC2. Besides, a combination of BIRC2 inhibitor (LCL161) and topotecan exerted synergistic effects on cancer cells and animal tumor models. With a pooled cohort of α7-HPV (including mixed infections with coexisting non-α7-HPV(s))-related cervical SCC treated between 1993 and 2014, high BIRC2 expression was associated with significantly worse outcome (cancer-specific survival, HR: 1.42; p = 0.008, progression-free survival, HR: 1.64; p = 0.005). Conclusions: These results suggest BIRC2 is a novel prognostic factor and therapeutic target for α7-HPV-related cervical SCC. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of surgery, radiation therapy and chemotherapy in the management of small cell carcinoma of the uterine cervix (SCCC) through a retrospective study of Taiwanese Gynecologic Oncology Group. Methods: We reviewed the medical records and histological files of 144 patients with FIGO stages IA-IIB SCCC treated in 11 main hospitals in Taiwan from 1987 to 2009. Results: There were 110 patients receiving primary surgery and 34 primary radiation therapy. Most patients in each group also received chemotherapy as part of primary treatment. A lower loco-regional failure rate was observed in patients who received primary radiation therapy than in those who had primary surgery (6% vs. 27%; P = 0.009). The 5-year overall survival (OS) was 89% for 13 surgically treated patients with cervical tumor ≤ 2 cm and no lymphovascular space involvement (LVSI) in whom recurrence was noted in 2 of 4 patients without receiving adjuvant chemotherapy and none in the 9 patients who had chemotherapy. Excluding these 13 patients, primary radiation therapy with at least 5 cycles of platinum-based chemotherapy (n = 14, including 12 stages IB2-IIB) resulted in a 5-year OS of 78%, better than that of 46% by primary surgery (n = 97, including 40 stages IB2-IIB) (P = 0.046). Conclusions: None of the 9 patients with cervical tumor ≤ 2 cm and no LVSI showed disease recurrence after primary surgery and adjuvant chemotherapy. For most patients with stages I-II, primary radiation therapy with aggressive chemotherapy was associated with better survival than surgery. [ABSTRACT FROM AUTHOR]