Glycemia and peak incremental indices of six popular fruits in Taiwan: healthy and Type 2 diabetes subjects compared

The aim of this study was to evaluate the glycemic index and peak incremental indices of six popular fruits in Taiwan, comparing healthy subjects (n = 20) and patients with Type 2 diabetes (n = 17). The six kinds of fruits tested were grapes, Asian pears, guavas, golden kiwifruit, lychees and bananas. Glycemic index values were tested according to the standard glycemic index testing protocol. The glycemic index and peak incremental indices were calculated according to published formulas. In Type 2 diabetes subjects, the glycemic index values of grapes, Asian pears, guavas, golden kiwifruit, lychees and bananas were 49.0 ± 4.5, 25.9 ± 2.9, 32.8 ± 5.2, 47.0 ± 6.5, 60.0 ± 8.0 and 41.3 ± 3.5. In healthy subjects, the glycemic index values were 49.1 ± 7.3, 18.0 ± 5.4, 31.1 ± 5.1, 47.3 ± 12.1, 47.9 ± 6.8 and 35.1 ± 5.6. There was no significant difference in glycemic index values between healthy and Type 2 diabetes subjects. There was also no significant difference in PII when comparing healthy subjects and subjects with Type 2 diabetes. In conclusion, glycemic index and peak incremental indices in healthy subjects can be approximately the same for Type 2 diabetes

Sequence variants of the aging gene CISD2 and the risk for Alzheimer's disease

Background/PurposeThe CISD2 gene has been related to life span control and mitochondrial dysfunction in animals. In addition, inhibition of mitochondrial enzymes due to an accumulation of beta-amyloid peptide has been related to Alzheimer's disease (AD). This study aimed to explore the association between sequence variants of the CISD2 gene and risk for AD, which has not been explored previously.MethodsThis was a case–control study involving a total of 276 patients with AD who were recruited from three teaching hospitals in Taiwan from 2007 to 2010; 460 controls were recruited from elderly individuals attending for health check-ups and volunteers in the hospital during the same period of time. All participants were aged 60 years or older. Two haplotype-tagging single nucleotide polymorphisms (htSNPs), rs223330 and rs223331, were selected from the CISD2 gene to test the association between their polymorphisms and the risk for dementia, and how ApoE ɛ4 status, sex, hypertension, and type 2 diabetes mellitus might modify this association.Resultsrs223330 variant carriage was not associated with risk for AD [TT versus CC: adjusted odds ratio (AOR) = 0.98, 95% confidence interval (CI) = 0.59–1.62; TC versus CC: AOR = 0.72, 95% CI = 0.47–1.11]. Similar findings were observed for rs223331 (AA versus TT: AOR = 1.12; AT versus TT: AOR = 0.99). In addition, hypertension significantly modified the association between rs223331 and risk for AD (p = 0.005).Three common haplotypes (with a frequency of 99.8%) were observed for CISD2. Common CISD2 haplotypes were not associated with the risk for AD.ConclusionOur findings suggested that CISD2 htSNPs are not associated with AD risk

EBV-encoded small RNA1 and nonresolving inflammation in rheumatoid arthritis

AbstractRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by perpetuated inflammation in multiple joints. To date, there is no cure for RA, and the causal factor for non-resolving inflammation in RA remains unclear. In this study, we initially observed expression of Epstein–Barr virus-encoded small RNA1 (EBER1) in the synovial tissue of all five patients who showed nonresolving RA inflammation. By contrast, EBER1 was detected in the synovial tissue of only one out of seven patients with advanced osteoarthritis (OA; p < 0.01, Fisher’s exact test). To confirm this finding, we conducted a second study on synovial tissue samples taken from 23 patients with nonresolving RA inflammation and 13 patients with OA. All synovial samples from patients with nonresolving inflammation of RA showed positive expression of EBER1 (23/23, 100%), whereas none of the synovial samples from patients with OA showed expression of EBER1 (0/13, 0%; p < 0.001, by Fisher’s exact test). In vitro, transfection of RA synovial fibroblasts with EBER1 induced the production of interleukin-6. Taken together, these data strongly suggest that nonresolving RA inflammation is strongly related to the presence of EBER1, which might be, at least partially, responsible for synovial fibroblast interleukin-6 production

Outcomes of patients with rodenticide poisoning at a far east poison center

BACKGROUND: Rodenticide poisoning remains a major public health problem in Asian countries. Nevertheless, very few data are available in world literature regarding the outcomes of these patients. Therefore, the purpose of this study was to investigate the clinical outcomes of rodenticide poisonings in our hospital and to compare these data with published reports from other international poison centers. FINDINGS: We retrospectively examined the records of 20 patients with rodenticide poisoning (8 brodifacoum, 12 bromadiolone) who were referred to Chang Gung Memorial Hospital between 2000 and 2011. It was found that most of the rodenticide patients were middle-aged adults. Both genders were equally affected and many patients had a past history of major depressive disorder or schizophrenia. Nevertheless, patients with bromadiolone were referred significantly sooner than patients with brodifacoum poisoning (0.1 ± 0.1 versus 5.5 ± 10.5, P < 0.001). Furthermore, it was found that patients with brodifacoum suffered higher incidences of ecchymosis (50.0% versus 0%, P = 0.006) and hematuria (50.0% versus 0%, P = 0.006) than patients with bromadiolone poisoning. Laboratory analysis also demonstrated a poorer hemostatic profile of patients with brodifacoum [prothrombin time (PT), international normalized ratio (INR), 4.3 ± 4.8 versus 1.0 ± 0.1, P = 0.032; PT prolongation, 50.0% versus 0%, P = 0.006; activated partial thromboplastin time (aPTT) prolongation, 50.0% versus 0%, P = 0.006] than patients with bromadiolone poisoning. At the end of analysis, no patient died of the poisoning. CONCLUSION: The favorable outcome (zero mortality rate) is comparable to the published reports from other international poison centers. Further studies are warranted

Association between the risk of lung cancer and influenza: A population-based nested case-control study

Background: Previous animal studies have shown that certain respiratory oncoviruses can lead to tumorigenesis, especially influenza virus. However, no clinical studies other than animal studies have been conducted to test this hypothesis. Objective: To investigate the association between influenza and the risk of lung cancer using the Taiwan Cancer Registry Database (TCRD) and Taiwan’s National Health Insurance Research Database (NHIRD). Methods: We identified a study cohort consisting of patients aged 40 years or above who were enrolled in the NHIRD between 1 January 2012 and 31 December 2014. Among them, we identified patients with lung cancer (cases) and their matched controls (matched by age, sex, and disease risk score (DRS) at a ratio of 1:10). Multivariate conditional logistic regression models were used to evaluate the association between exposure to influenza (timing and cumulative number) and risk of lung cancer. Results: We identified 32,063 cases and 320,627 matched controls. Influenza was associated with a 1.09-fold increased risk of lung cancer (aOR 1.09, 95% CI 1.04–1.14, p<0.0001). The risk of lung cancer increased slightly with cumulative exposure to influenza (1–2 exposures: aOR 1.05, 95% CI 1.00–1.11; 3-4 exposures: aOR 1.12, 95% CI 1.00–1.25; 5+ exposures: aOR 1.25, 95% CI 1.13–1.39). Conclusion: Exposure to influenza was associated with an increased risk of lung cancer and the risk increased with cumulative exposure to influenza. However, the lack of valid information on smoking could lead to confounding, and future studies collecting patients’ smoking histories are warranted to validate the association between influenza and lung cancer

Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.

Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high resolution along 30 Mb of the human genome and found that active promoters are marked by trimethylation of Lys4 of histone H3 (H3K4), whereas enhancers are marked by monomethylation, but not trimethylation, of H3K4. We developed computational algorithms using these distinct chromatin signatures to identify new regulatory elements, predicting over 200 promoters and 400 enhancers within the 30-Mb region. This approach accurately predicted the location and function of independently identified regulatory elements with high sensitivity and specificity and uncovered a novel functional enhancer for the carnitine transporter SLC22A5 (OCTN2). Our results give insight into the connections between chromatin modifications and transcriptional regulatory activity and provide a new tool for the functional annotation of the human genome. Activation of eukaryotic gene transcription involves the coordination of a multitude of transcription factors and cofactors on regulatory DNA sequences such as promoters and enhancers and on the chromatin structure containing these elements 1-3 . Promoters are located at the 5¢ ends of genes immediately surrounding the transcriptional start site (TSS) and serve as the point of assembly of the transcriptional machinery and initiation of transcription 4 . Enhancers contribute to the activation of their target genes from positions upstream, downstream or within a target or neighboring gene Recent investigations using chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) experiments have described the chromatin architecture of transcriptional promoters in yeast, fly and mammalian systems 9 . In a manner largely conserved across species, active promoters are marked by acetylation of various residues of histones H3 and H4 and methylation of H3K4, particularly trimethylation of this residue. Nucleosome depletion is also a general characteristic of active promoters in yeast and flies, although this feature remains to be thoroughly examined in mammalian systems. Although some studies suggest that distal regulatory elements like enhancers may be marked by similar histone modification patterns 10-13 , the distinguishing chromatin features of promoters and enhancers have yet to be determined, hindering our understanding of a predictive histone code for different classes of regulatory elements. Here, we present high-resolution maps of multiple histone modifications and transcriptional regulators in 30 Mb of the human genome, demonstrating that active promoters and enhancers are associated with distinct chromatin signatures that can be used to predict these regulatory elements in the human genome. RESULTS Chromatin architecture and transcription factor localization We performed ChIP-chip analysis 14 to determine the chromatin architecture along 44 human loci selected by the ENCODE consortium as common targets for genomic analysis 15 , totaling 30 Mb

Expression of ezrin is associated with invasion and dedifferentiation of hepatitis B related hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the fifth most common malignancy in the world and constitutes the leading cause of cancer-related death among men, and second among women in Taiwan. Liver cirrhosis and HCC are relatively prevalent, and 80% to 85% of the patients with these conditions have positive results for hepatitis B surface antigen in Taiwan. Only 5% of the general population is seronegative for all hepatititis B virus (HBV) markers. This is the first study to determine the role of ezrin upon HBV HCC cell and patients with HBV HCC undergoing hepatectomy</p> <p>Methods</p> <p>Immunohistochemical study with ezrin in 104 human HBV-HCC cases were carried out to investigate its association with the clinicopathological features and the outcomes of 104 HBV-HCC patients undergoing hepatetomy. In addition, DNA constructs including the wild type ezrin (wt-ezrin) and mutant ezrin Tyr353 (Y353) were transfected into Hep3B cell to study its role in tumor invasion and differentiation.</p> <p>Results</p> <p>HBV HCC patients with ezrin over-expression independently have smaller tumor size, cirrhotic liver background, poor tumor differentiation, and more vascular invasion. Ezrin expression status has no impact on survival for HBV-HCC patients undergoing hepatectomy. The in vitro assay showed that wt-ezrin Hep3B cells have a significant higher level of AFP secretion and higher invasion ability as compared with the control and Y353- ezrin Hep3B cells.</p> <p>Conclusion</p> <p>Ezrin over-expression contributed to de-differentiation and invasion of HBV-HCC cell. HBV-HCC patients with ezrin over-expression were independently associated with tumor with smaller size, cirrhotic liver background, poor differentiation, and vascular invasion.</p

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie