Population-based proband-oriented pedigree information system: application to hypertension with population-based screening data (KCIS No. 25)

Objective To develop a population-based probandoriented pedigree information system that can be easily applied to various diseases in genetic epidemiological studies, making allowance for the capture of theoretical family relationships. Designs and Measurements A population-based proband-oriented pedigree information system with ties of consanguinity based on both population-based household registry data and Keelung Community Integrated Screening data was proposed to build a comprehensive extended family pedigree structure to accommodate a series of genetic studies on different diseases. We also developed an algorithm to efficiently assess how well theoretical family relationships affecting the occurrence of diseases across three generations with respect to the relative relationship score, a quantitative indicator of genetic influence, were captured. Results We applied this population-based probandoriented pedigree information system to estimate the rate of hypertension with various relative relationships given the selection of probands. The degree of capturing complete familial relationships was assessed for three generations. The risk for early onset of hypertension was proportional to the proband-oriented relative relationship score with 2% increased risk and 1% correction for incomplete capture. Conclusions The population-based proband-oriented pedigree information system is powerful and can support various genetic descriptive and analytic epidemiological studies

Characteristics, survival, and related factors of newly diagnosed colorectal cancer patients refusing cancer treatments under a universal health insurance program

BACKGROUND: Colorectal cancer is the third most commonly diagnosed cancer worldwide. Few studies have addressed the causes and risks of treatment refusal in a universal health insurance setting. METHODS: We examined the characteristics and survival associated with treatment refusal in patients with newly diagnosed colorectal cancer in Taiwan during 2004–2008. Treatment refusal was defined as not undergoing any cancer treatment within 4 months of confirmed cancer diagnosis. Patient data were extracted from four national databases. Factors associated with treatment refusal were identified through logistic regression using the generalized estimating equation method, and survival analysis was performed using the Cox proportional hazards model. RESULTS: Of the 41,340 new colorectal cancer cases diagnosed, 3,612 patients (8.74%) refused treatment. Treatment refusal rate was higher in patients with less urbanized areas of residence, lower incomes, preexisting catastrophic illnesses, cancer stages of 0 and IV, and diagnoses at regional and district hospitals. Logistic regression analysis revealed that patients aged >75 years were the most likely to refuse treatment (OR, 1.87); patients with catastrophic illnesses (OR, 1.66) and stage IV cancer (OR, 1.43) had significantly higher refusal rates. The treatment refusers had 2.66 times the risk of death of those who received treatment. Factors associated with an increased risk of death in refusers included age ≥75 years, insured monthly salary ≥22,801 NTD, low-income household or aboriginal status, and advanced cancer stage (especially stage IV; HR, 11.33). CONCLUSION: Our results show a lower 5-year survival for colorectal patients who refused treatment than for those who underwent treatment within 4 months. An age of 75 years or older, low-income household status, advanced stages of cancer, especially stage IV, were associated with higher risks of death for those who refused treatment

Application of Scutellariae radix

Salmonella enterica serovar Choleraesuis, a host-adapted pathogen of swine, usually causes septicemia. Lactic acid bacteria (LAB) strains have been widely studied in recent years for their probiotic properties. In this study, a mouse infection model first screened for potential agents against infection, then a pig infection model evaluated effects of LAB strains and herbal plants against infection. Scutellariae radix (SR) and Gardeniae fructus (GF) showed abilities to reduce bacteria shedding and suppressing serum level of TNF-α induced by infection in swine. Bioactivities of SR and GF were enhanced by combining with LAB strains, which alone could speed up the bacteria elimination time in feces and boost immunity of infected pigs. Baicalein and genipin exhibited stronger cytotoxicity than baicalin and geniposide did, as well as prevent Salmonella from invading macrophages. Our study suggests LAB strains as exhibiting multiple functions: preventing infection, enhancing immunity to prepare host defenses against further infection, and adjusting intestinal microbes’ enzymatic activity in order to convert herbal compounds to active compounds. The SR/GF-LAB strain mixture holds potential infection-prevention agents supplied as feed additives

Long-Term Storage Effects on Stability of Aβ1–40, Aβ1–42, and Total Tau Proteins in Human Plasma Samples Measured with Immunomagnetic Reduction Assays

Background: The stability of Alzheimer’s disease (AD) biomarkers in plasma, measured by immunomagnetic reduction (IMR) after long-term storage at –80°C, has not been established before. Method: Ninety-nine human plasma samples from 53 normal controls (NCs), 5 patients with amnestic mild cognitive impairment (aMCI), and 41 AD patients were collected. Each plasma sample was aliquoted and stored as single-use aliquots at –80°C. The baseline measurements for Aβ1–40, Aβ1–42, and total Tau protein (T-Tau) concentrations for each sample were done within 3 months of blood draw by IMR. They are referred to as baseline concentrations. A separate aliquot from each sample was assayed with IMR to assess the stability of the measured analytes during storage at –80°C between 1.1 and 5.4 years. This is referred to as a repeated result. Results: IMR shows that plasma levels of Aβ1–40 and Aβ1–42 exhibit stability over 5-year storage at –80°C and that plasma levels of T-Tau are less stable (approximately 1.5 years). Conclusion: Although the measured concentrations of T-Tau in human plasma may alter during storage, the diagnostic utility of the results are only slightly affected when the product of Aβ1–42 and T-Tau concentrations are used. The results show that the overall agreement between baseline and repeated measurements in the ability of discriminating NCs from aMCI/AD patients is higher than 80%

Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats

BACKGROUND: Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats. METHODS: Type 1 diabetes mellitus was induced in Sprague–Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nω-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats. RESULTS: Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (l-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals. CONCLUSIONS: CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals