Synthesis,Structural and Antioxidant Studies of Some Novel N-Ethyl Phthalimide Esters

A series of N-ethyl phthalimide esters 4(a-n) were synthesized and characterized by spectroscopic studies. Further, the molecular structure of majority of compounds were analysed by single crystal X-ray diffraction studies. The X-ray analysis revealed the importance of substituents on the crystal stability and molecular packing. All the synthesized compounds were tested for in vitro antioxidant activity by DPPH radical scavenging, FRAP and CUPRAC methods. Few of them have shown good antioxidant activity.     

Early Detection for Cases of Enterovirus- and Influenza-Like Illness through a Newly Established School-Based Syndromic Surveillance System in Taipei,January 2010 ~ August 2011

School children may transmit pathogens with cluster cases occurring on campuses and in families. In response to the 2009 influenza A (H1N1) pandemic, Taipei City Government officials developed a School-based Infectious Disease Syndromic Surveillance System (SID-SSS). Teachers and nurses from preschools to universities in all 12 districts within Taipei are required to daily report cases of symptomatic children or sick leave requests through the SID-SSS. The pre-diagnosis at schools is submitted firstly as common pediatric disease syndrome-groups and re-submitted after confirmation by physicians. We retrieved these data from January 2010 to August 2011 for spatio-temporal analysis and evaluated the temporal trends with cases obtained from both the Emergency Department-based Syndromic Surveillance System (ED-SSS) and the Longitudinal Health Insurance Database 2005 (LHID2005). Through the SID-SSS, enterovirus-like illness (EVI) and influenza-like illness (ILI) were the two most reported syndrome groups (77.6% and 15.8% among a total of 19,334 cases, respectively). The pre-diagnosis judgments made by school teachers and nurses showed high consistency with physicians’ clinical diagnoses for EVI (97.8%) and ILI (98.9%). Most importantly, the SID-SSS had better timeliness with earlier peaks of EVI and ILI than those in the ED-SSS. Furthermore, both of the syndrome groups in these two surveillance systems had the best correlation reaching 0.98 and 0.95, respectively (p<0.01). Spatio-temporal analysis observed the patterns of EVI and ILI both diffuse from the northern suburban districts to central Taipei, with ILI spreading faster. This novel system can identify early suspected cases of two important pediatric infections occurring at schools, and clusters from schools/families. It was also cost-effective (95.5% of the operation cost reduced and 59.7% processing time saved). The timely surveillance of mild EVI and ILI cases integrated with spatial analysis may help public health decision-makers with where to target for enhancing surveillance and prevention measures to minimize severe cases.     

Abacus Training Affects Math and Task Switching Abilities and Modulates Their Relationships in Chinese Children

Our previous work demonstrated that abacus-based mental calculation (AMC), a traditional Chinese calculation method, could help children improve their math abilities (e.g. basic arithmetical ability) and executive function (e.g. working memory). This study further examined the effects of long-term AMC training on math ability in visual-spatial domain and the task switching component of executive function. More importantly, this study investigated whether AMC training modulated the relationship between math abilities and task switching. The participants were seventy 7-year-old children who were randomly assigned into AMC and control groups at primary school entry. Children in AMC group received 2-hour AMC training every week since primary school entry. On the contrary, children in the control group had never received any AMC training. Math and task switching abilities were measured one year and three years respectively after AMC training began. The results showed that AMC children performed better than their peers on math abilities in arithmetical and visual-spatial domains. In addition, AMC group responded faster than control group in the switching task, while no group difference was found in switch cost. Most interestingly, group difference was present in the relationships between math abilities and switch cost. These results implied the effect of AMC training on math abilities as well as its relationship with executive function.     

Racial differences in genome-wide methylation profiling and gene expression in breast tissues from healthy women

Breast cancer is more common in European Americans (EAs) than in African Americans (AAs) but mortality from breast cancer is higher among AAs. While there are racial differences in DNA methylation and gene expression in breast tumors, little is known whether such racial differences exist in breast tissues of healthy women. Genome-wide DNA methylation and gene expression profiling was performed in histologically normal breast tissues of healthy women. Linear regression models were used to identify differentially-methylated CpG sites (CpGs) between EAs (n = 61) and AAs (n = 22). Correlations for methylation and expression were assessed. Biological functions of the differentially-methylated genes were assigned using the Ingenuity Pathway Analysis. Among 485 differentially-methylated CpGs by race, 203 were hypermethylated in EAs, and 282 were hypermethylated in AAs. Promoter-related differentially-methylated CpGs were more frequently hypermethylated in EAs (52%) than AAs (27%) while gene body and intergenic CpGs were more frequently hypermethylated in AAs. The differentially-methylated CpGs were enriched for cancer-associated genes with roles in cell death and survival, cellular development, and cell-to-cell signaling. In a separate analysis for correlation in EAs and AAs, different patterns of correlation were found between EAs and AAs. The correlated genes showed different biological networks between EAs and AAs; networks were connected by Ubiquitin C. To our knowledge, this is the first comprehensive genome-wide study to identify differences in methylation and gene expression between EAs and AAs in breast tissues from healthy women. These findings may provide further insights regarding the contribution of epigenetic differences to racial disparities in breast cancer.     

Human Ghrelin Mitigates Intestinal Injury and Mortality after Whole Body Irradiation in Rats

Widespread use of ionizing radiation has led to the realization of the danger associated with radiation exposure. Although studies in radiation countermeasures were initiated a half century ago, an effective therapy for a radiomitigator has not been identified. Ghrelin is a gastrointestinal hormone, and administration of ghrelin is protective in animal models of injuries including radiation combined injury. To test whether ghrelin can be protective in whole body irradiaton (WBI) alone, male Sprague Dawley (SD) rats were treated with human ghrelin (20 nmol/rat) daily for 6 days starting at either 24 h or 48 h after 10 Gray (Gy) WBI and survival outcome was examined. The 10 Gy WBI produced a LD^70/30 model in SD rats (30% survival in 30 days). The survival rate in rats treated with ghrelin starting at 24 h was significantly improved to 63% and when treatment was initiated at 48 h, the survival remained at 61%. At 7 days post WBI, plasma ghrelin was significantly reduced from the control value. Ghrelin treatment starting at 24 h after WBI daily for 6 days improved histological appearance of the intestine, reduced gut permeability, serum endotoxin levels and bacterial translocation to the liver by 38%, 42% and 61%, respectively at day 7 post WBI. Serum glucose and albumin were restored to near control levels with treatment. Ghrelin treatment also attenuated WBI-induced intestinal apoptosis by 62% as evidenced by TUNEL staining. The expression of anti-apoptotic cell regulator Bcl-xl was decreased by 38% in the vehicle and restored to 75% of the control with ghrelin treatment. Increased expression of intestinal CD73 and pAkt were observed with ghrelin treatment, indicating protection of the intestinal epithelium after WBI. These results indicate that human ghrelin attenuates intestinal injury and mortality after WBI. Thus, human ghrelin can be developed as a novel mitigator for radiation injury.     

Overexpression of BIRC6 Is a Predictor of Prognosis for Colorectal Cancer

MethodsWe used Western blotting and immunohistochemistry to examine BIRC6 expression in 7 CRC cell lines and 126 CRC clinical samples. We determined the biological significance of BIRC6 in CRC cell lines by a lentivirus-mediated silencing method.ResultsWe reported that BIRC6 was overexpressed in CRC cell lines and clinical CRC tissues. BIRC6 overexpression was correlated with tumor size and invasion depth of CRC. BIRC6 overexpression is associated with worse overall survival (OS) (P = 0.001) and shorter disease-free survival (DFS) (P = 0.010). BIRC6 knockdown inhibited cell proliferation, arrested cell cycle at S phase, downregulated cyclin A2, B1, D1 and E1 levels, and sensitized CRC cells to chemotherapy in vitro and in vivo.ConclusionsTaken together, these data suggests that BIRC6 overexpression is a predictor of poor prognosis in colorectal cancer and BIRC6 could be a potential target of CRC therapy.     

Risk of Shingles in Adults with Primary Sjogren’s Syndrome and Treatments: A Nationwide Population-Based Cohort Study

Background

Primary Sjögren''s syndrome (pSS) is associated with immunological dysfunctions—a well-known risk factor of shingles. This study aimed to examine the incidence and risk of shingles in adults with pSS and pharmacological treatments.

Methods

This retrospective population-based cohort study was conducted using National Health Insurance claims data. Using propensity scores, 4,287 pSS adult patients and 25,722-matched cohorts by age, gender, selected comorbidities and Charlson comorbidity index scores were identified. Kaplan-Meier analysis and Cox regression were conducted to compare the differences in developing shingles. In pSS, oral and eye dryness are treated with substitute agents. Extraglandular features are often treated with pharmacological drugs including steroids and immunosuppressants. pSS patients were grouped as follows: no pharmacological drugs, steroids alone; immunosuppressants alone; combined therapies.

Results

During the follow-up, 463 adults with pSS (10.80%) and 1,345 control cohorts (5.23%) developed shingles. The cumulative incidence of shingles in pSS patients (18.74/1,000 patient-years) was significantly higher than controls (8.55/1,000 patient-years). The adjusted hazard ratio (HR) of shingles was 1.69 (95% confidence interval (CI) 1.50–1.90). In age-subgroup analyses, incidences of shingles in pSS increased with age and peaked in pSS patients aged ≧60; however, adjusted HRs decreased with age. Compared to control cohorts with no drugs, adjusted HRs for shingles in pSS patients were ranked from high to low as: combined therapies (4.14; 95% CI 3.14–5.45) > immunosuppressants alone (3.24; 95% CI 2.36–4.45) > steroids alone (2.54; 95% CI 2.16–2.97) > no pharmacological drugs (2.06; 95% CI 1.76–2.41). Rates of shingles-associated hospitalization and postherpetic neuralgia were 5.62% and 24.41%, both of which were significantly higher than those (2.60%; 13.01%) in the control cohorts.

Conclusions

Adults with pSS were at greater risk for shingles than control cohorts. Drug exposures significantly increased the risk of shingles in pSS.