Spatiotemporal Trends in Oral Cancer Mortality and Potential Risks Associated with Heavy Metal Content in Taiwan Soil

Central and Eastern Taiwan have alarmingly high oral cancer (OC) mortality rates, however, the effect of lifestyle factors such as betel chewing cannot fully explain the observed high-risk. Elevated concentrations of heavy metals in the soil reflect somewhat the levels of exposure to the human body, which may promote cancer development in local residents. This study assesses the space-time distribution of OC mortality in Taiwan, and its association with prime factors leading to soil heavy metal content. The current research obtained OC mortality data from the Atlas of Cancer Mortality in Taiwan, 1972–2001, and derived soil heavy metals content data from a nationwide survey carried out by ROCEPA in 1985. The exploratory data analyses showed that OC mortality rates in both genders had high spatial autocorrelation (Moran’s I = 0.6716 and 0.6318 for males and females). Factor analyses revealed three common factors (CFs) representing the major pattern of soil pollution in Taiwan. The results for Spatial Lag Models (SLM) showed that CF1 (Cr, Cu, Ni, and Zn) was most spatially related to male OC mortality which implicates that some metals in CF1 might play as promoters in OC etiology

L-Arginine and L-Citrulline Supplementation Have Different Programming Effect on Regulatory T-Cells Function of Infantile Rats

Arginine is a semiessential amino acid in healthy adult human, but is essential for preterm, newborn or critically ill patients. Arginine can be supplied from our diet or de novo synthesis from citrulline. In conditions of sepsis or endotoxemia, arginine may be deficient and be accompanied with altered immune response. L-arginine supplementation can ameliorate dysregulated immune condition and improve prognosis. Many studies had tried L-arginine or L-citrulline supplementation to examine the effect on immune response in the adult population. Few had studied on the young children. In this study, we determined the effect of L-arginine and L-citrulline supplementation on the immune response of infantile rats. Male infantile rats received normal saline, L-arginine (200 mg/kg/day) or L-citrulline (200 mg/kg/day) intraperitoneally over postnatal day 8 to day 14. The infantile rats were then sacrificed. The blood was analyzed while the spleen was indicated for immune analysis after stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS). We found L-arginine supplementation enhanced Th1 immune response by increasing IFN-γ production. Both the L-arginine and L-citrulline therapy can modulate regulatory T-cell (Treg) immune effects by increasing the IL-10 level. Only the L-citrulline group showed a TGF-β1 increase. Both L-arginine and L-citrulline therapy were also noted to decrease SMAD7 expression and enhance SIRT-1 abundance. However, FOXP3 expression was only modulated by L-citrulline treatment. We then concluded that L-arginine and L-citrulline supplementation can modulate the regulatory T-cells function differently for infantile rats

Novel Ultrasonographic Fatty Liver Indicator Can Predict Hepatitis in Children With Non-alcoholic Fatty Liver Disease

Background: Childhood non-alcoholic fatty liver disease (NAFLD) is a public health issue worldwide. To date, liver biopsy remains the gold standard for diagnosing the severity of NAFLD. However, this invasive procedure might contribute to complications. Owing to this reason, a good non-invasive tool to estimate NAFLD in children is urgently needed. We sought to investigate whether a non-invasive semi-quantitative ultrasonographic fatty liver indicator (US-FLI) can estimate NAFLD in children.Methods: Children aged between 10 and 18 years were enrolled prospectively. Abdominal ultrasonography was performed by a single experienced pediatric gastroenterologist and the non-invasive semi-quantitative US-FLI score were used. Patients were diagnosed with NAFLD if they had a US-FLI score ≥2. The anthropometric measures, obesity-related biochemical results, and levels of tumor necrosis factor-α, interleukin-6, caspase-cleaved cytokeratin fragment of cytokeratin 18 (M30), and adiponectin were also checked.Results: Overall, 117 children aged 10–18 years were enrolled. The anthropometric measures and obesity-related biochemical parameters (hsCRP, triglyceride, uric acid, AST, ALT, γ-GT, homeostatic model assessment insulin resistance (HOMA-IR), and M30) were significantly higher in the obesity group than in the non-obesity group (p < 0.05). Similarly, the US-FLI score was significantly higher in the obesity group than that in the non-obesity group (p < 0.001). Multiple linear regression showed that the US-FLI score was significantly associated with the waist-to-height ratio, uric acid, adiponectin, and M30 levels (all p < 0.05) in children with obesity. The US-FLI score ≥6 was the optimal cut-off point for predicting the hepatitis in children with NAFLD. The area under the receiver operating characteristic curve was 0.710 (95% CI: 0.572–0.847; p = 0.005).Conclusions: The non-invasive US-FLI score can predict hepatitis in children with NAFLD without mandatory liver biopsy. Moreover, the waist-to-height ratio, uric acid, adiponectin, and M30 levels were significantly associated with US-FLI score in children with obesity

Granulocyte Colony-Stimulating Factor Alleviates Bacterial-Induced Neuronal Apoptotic Damage in the Neonatal Rat Brain through Epigenetic Histone Modification

Bacterial meningitis during the perinatal period may cause long-term neurological deficits. The study investigated whether bacterial lipopolysaccharide (LPS) derived from E. coli. led to neuronal apoptosis with an impaired performance of long-term cognitive function involving the activation of histone modification in the TNF-α gene promoter. Further, we looked into the therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) in a neonatal brain suffering from perinatal bacterial meningitis. We applied the following research techniques: neurobehavioral tasks, confocal laser microscopy, chromatin immunoprecipitation, and Western blotting. At postnatal day 10, the animals were subjected to LPS and/or G-CSF. The target brain tissues were then collected at P17. Some animals (P45) were studied using neurobehavioral tasks. The LPS-injected group revealed significantly increased expression of NF-κB phosphorylation and trimethylated H3K4 in the TNFA gene promoter locus. Furthermore, the caspase-3, neuronal apoptosis expression, and an impaired performance in cognitive functions were also found in our study. Such deleterious outcomes described above were markedly alleviated by G-CSF therapy. This study suggests that selective therapeutic action sites of G-CSF through epigenetic regulation in the TNFA gene promoter locus may exert a potentially beneficial role for the neonatal brain suffering from perinatal bacterial-induced meningitis

Incidence of oral cancer in relation to nickel and arsenic concentrations in farm soils of patients' residential areas in Taiwan

<p>Abstract</p> <p>Background</p> <p>To explore if exposures to specific heavy metals in the environment is a new risk factor of oral cancer, one of the fastest growing malignancies in Taiwan, in addition to the two established risk factors, cigarette smoking and betel quid chewing.</p> <p>Methods</p> <p>This is an observational study utilized the age-standardized incidence rates of oral cancer in the 316 townships and precincts of Taiwan, local prevalence rates of cigarette smoking and betel quid chewing, demographic factors, socio-economic conditions, and concentrations in farm soils of the eight kinds of heavy metal. Spatial regression and GIS (Geographic Information System) were used. The registration contained 22,083 patients, who were diagnosed with oral cancer between 1982 and 2002. The concentrations of metal in the soils were retrieved from a nation-wide survey in the 1980s.</p> <p>Results</p> <p>The incidence rate of oral cancer is geographically related to the concentrations of arsenic and nickel in the patients' residential areas, with the prevalence of cigarette smoking and betel quid chewing as controlled variables.</p> <p>Conclusions</p> <p>Beside the two established risk factors, cigarette smoking and betel quid chewing, arsenic and nickel in farm soils may be new risk factors for oral cancer. These two kinds of metal may involve in the development of oral cancer. Further studies are required to understand the pathways via which metal in the farm soils exerts its effects on human health.</p

Polygenic risk scores for prediction of breast cancer risk in Asian populations.

PURPOSE: Non-European populations are under-represented in genetics studies, hindering clinical implementation of breast cancer polygenic risk scores (PRSs). We aimed to develop PRSs using the largest available studies of Asian ancestry and to assess the transferability of PRS across ethnic subgroups. METHODS: The development data set comprised 138,309 women from 17 case-control studies. PRSs were generated using a clumping and thresholding method, lasso penalized regression, an Empirical Bayes approach, a Bayesian polygenic prediction approach, or linear combinations of multiple PRSs. These PRSs were evaluated in 89,898 women from 3 prospective studies (1592 incident cases). RESULTS: The best performing PRS (genome-wide set of single-nucleotide variations [formerly single-nucleotide polymorphism]) had a hazard ratio per unit SD of 1.62 (95% CI = 1.46-1.80) and an area under the receiver operating curve of 0.635 (95% CI = 0.622-0.649). Combined Asian and European PRSs (333 single-nucleotide variations) had a hazard ratio per SD of 1.53 (95% CI = 1.37-1.71) and an area under the receiver operating curve of 0.621 (95% CI = 0.608-0.635). The distribution of the latter PRS was different across ethnic subgroups, confirming the importance of population-specific calibration for valid estimation of breast cancer risk. CONCLUSION: PRSs developed in this study, from association data from multiple ancestries, can enhance risk stratification for women of Asian ancestry

European polygenic risk score for prediction of breast cancer shows similar performance in Asian women

Abstract: Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Nonobstructive Dilation of Urinary Tract and Later Development of Obstruction: Report of One Case

Cases of nonobstructive dilation of the upper urinary tract subsequently becoming obstructive are rare. We report a case involving a male child approximately 2.5 years old (29 months) who presented with an obstruction of the ureterovesical junction, which had been diagnosed and treated for nonobstructive dilation at another hospital 15 months earlier. At our hospital, we found no ureteral orifice by cystoscopic examination. Exploratory surgery was performed and complete obstruction of the ureterovesical junction was observed. We resected the segment involved in the obstruction and performed an ureteroneocystostomy. Patients found to have nonobstructive dilation of the urinary tract, a common and often innocuous finding, need careful follow-up to ensure that obstructions that may develop later can be treated in a timely manner