Potential functionality and digestibility of oryzanol as determined using in vitro cell culture models

A mouse lymphatic endothelial cell (SVEC4-10) model and a human intestinal cell (C2BBe1) model in vitro were developed and capable to be used to study antioxidant activity, hypocholesterolemic capability and digestibility of γ-oryzanol. The critical and vital parameters in developing these cell models were the emulsion preparation of hydrophobic compounds for cell models, the consistent management of cell culture, and the selection of cell viability detection methods compatible with the cell lines and the test substances. The results showed that, in some situations, γ-oryzanol could present a more effective antioxidant activity than α-tocopherol, in terms of reducing tert-butyl hydroperoxide promoted oxidative damage on cellular mitochondrial activity. After 1-hour oxidation, cell viability was 81.8% when incubated with γ-oryzanol, compared to 54.5% with the control and 74.6% with α-tocopherol. The three major components of γ-oryzanol, cycloartenyl ferulate, 24-methylene cycloartanyl ferulate and campesteryl ferulate, generally had higher antioxidant activity than γ-oryzanol and among them, 24-methylene cycloartanyl ferulate was found to be relatively more effective and could be more powerful than α-tocopherol. A synergistic antioxidant activity among γ-oryzanol, ferulic acid and α-tocopherol was also found. With regard to the hypocholesterolemic capacity of γ-oryzanol, the results suggested that the intact γ-oryzanol was poorly absorbed by intestinal cells in vitro. Therefore, it was speculated that the effect of γ-oryzanol might take place in the lumen of gastrointestinal tract, possibly by means of reducing the micellar solubility of cholesterol and cholesteryl esters and inhibiting cholesterol esterase-facilitated cholesteryl ester hydrolysis. The results showed that preincubation of cholesterol and γ-oryzanol for six hours significantly reduced the cholesterol uptake into cells. γ-Oryzanol also showed a trend towards inhibition of cholesteryl esterase, which is responsible for hydrolyzing cholesteryl esters to free cholesterol before uptake. The results of in vitro digestibility studies of γ-oryzanol showed that the ester bond of γ-oryzanol, especially campesteryl ferulate and sitosteryl ferulate, was broken down by cholesterol esterase and produced triterpene alcohols or sterols and ferulic acid, which were further degraded. The degradation of γ-oryzanol in the stomach may undergo a different pathway because sterols or triterpene alcohols were also not found after peptic digestion

Effects of Extreme Precipitation to the Distribution of Infectious Diseases in Taiwan, 1994–2008

The incidence of extreme precipitation has increased with the exacerbation of worldwide climate disruption. We hypothesize an association between precipitation and the distribution patterns that would affect the endemic burden of 8 infectious diseases in Taiwan, including water- and vector-borne infectious diseases. A database integrating daily precipitation and temperature, along with the infectious disease case registry for all 352 townships in the main island of Taiwan was analysed for the period from 1994 to 2008. Four precipitation levels, <130 mm, 130–200 mm, 200–350 mm and >350 mm, were categorized to represent quantitative differences, and their associations with each specific disease was investigated using the Generalized Additive Mixed Model and afterwards mapped on to the Geographical Information System. Daily precipitation levels were significantly correlated with all 8 mandatory-notified infectious diseases in Taiwan. For water-borne infections, extreme torrential precipitation (>350 mm/day) was found to result in the highest relative risk for bacillary dysentery and enterovirus infections when compared to ordinary rain (<130 mm/day). Yet, for vector-borne diseases, the relative risk of dengue fever and Japanese encephalitis increased with greater precipitation only up to 350 mm. Differential lag effects following precipitation were statistically associated with increased risk for contracting individual infectious diseases. This study’s findings can help health resource sector management better allocate medical resources and be better prepared to deal with infectious disease outbreaks following future extreme precipitation events

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase&nbsp;1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation&nbsp;disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age&nbsp; 6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score&nbsp; 652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc&nbsp;= 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N&nbsp;= 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in&nbsp;Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in&nbsp;Asia&nbsp;and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Comparative Analysis of Urinary N7-(2-Hydroxyethyl)Guanine for Ethylene Oxide- and Non-Exposed Workers

Ethylene oxide (EO), a direct alkylating agent and a carcinogen, can attack the nucleophilic sites of DNA bases to form a variety of DNA adducts. The most abundant adduct, N7-(2-hydroxyethyl)guanine (N7-HEG), can be depurinated spontaneously or enzymatically from DNA backbone to form abasic sites. Molecular dosimetry of the excised N7-HEG in urine can serve as an EO exposure and potential risk- associated biomarker. This study was to analyze N7-HEG in urine collected from 89 EO-exposed and 48 nonexposed hospital workers and 20 exposed and 10 nonexposed factory workers by using our newly developed on-line solid-phase extraction isotope-dilution LC-MS/MS method. Statistical analysis of data shows that the exposed factory workers excreted significantly greater concentrations of N7-HEG than both the nonexposed factory workers and hospital workers. Multiple linear regression analysis reveals that the EO- exposed factory workers had a significantly greater post- shift urinary N7-HEG than their nonexposed coworkers and hospital workers. These results demonstrate that analysis of urinary N7-HEG can serve as a biomarker of EO exposure for future molecular epidemiology studies to better understand the role of the EO-induced DNA adduct formation in EO carcinogenicity and certainly for routine surveillance of occupational EO exposure for the study of potential health impacts on workers

Withdrawal from long-term hemodialysis in patients with end-stage renal disease in Taiwan

Withdrawal from dialysis is ethically appropriate for some patients with multiple comorbidities and a shortened life expectancy. Taiwan has the highest prevalence of dialysis patients in the world, and the National Health Insurance (NHI) program offers renal replacement therapy free of charge. In this review, we discuss its current status and many background issues related to withdrawing dialysis from patients with advanced renal failure in Taiwan. Compared with dialysis therapy, the medical resources for hospice care are relatively sparse. Since the announcement of the Statute for Palliative Care in 2000, there has been a gradual improvement in the laws and health polices supporting dialysis withdrawal. Culture and social customs also have a significant impact on the practice of hospice care. Based on current evidence and in accordance with the local environment, we propose recommendations for the clinical practice of dialysis withdrawal and hospice care. There remains a need to expand upon the community-based hospice care and home care systems to better serve patients. In conclusion, there are cross-cultural differences relating to dialysis withdrawal between Taiwan and Western countries. Our experience and clinical recommendations may be helpful for the countries with NHI systems or for the Eastern countries

Establishment of a renal supportive care program: Experience from a rural community hospital in Taiwan

Renal supportive care (RSC) denotes a care program dedicated for patients with acute, chronic renal failure, and end-stage renal disease (ESRD), aiming to offer maximal symptom relief and optimize patients' quality of life. The uncertainty of prognosis for patients with chronic kidney disease and ESRD, the sociocultural issues inherent to the Taiwanese society, and the void of structured and practical RSC pathway, contributes to the underrecognition and poor utilization of RSC. Taiwanese patients rarely receive information regarding RSC as part of a standardized care and are not commonly offered this option. In National Taiwan University Hospital Jinshan branch, we started a RSC subprogram, supported by the community-based palliative/hospice care main program. We focused on understanding the need and providing the choice of RSC to suitable candidates. A three-step and four-phase protocol was designed and implemented to identify appropriate patients and to enhance the applicability of the RSC. We harnessed family visit and home-based family meeting as a vehicle to understand the patients' preferences, to discover what ESRD patients and their family value most, and to introduce the option of RSC. In the current review, we described our pilot experience of establishing a RSC program in Taiwan, and discuss its potential advantage