Variable Classifications of Glycemic Index Determined by Glucose Meters

The study evaluated and compared the differences of glucose responses, incremental area under curve (IAUC), glycemic index (GI) and the classification of GI values between measured by biochemical analyzer (Fuji automatic biochemistry analyzer (FAA)) and three glucose meters: Accue Chek Advantage (AGM), BREEZE 2 (BGM), and Optimum Xceed (OGM). Ten healthy subjects were recruited for the study. The results showed OGM yield highest postprandial glucose responses of 119.6 ± 1.5, followed by FAA, 118.4 ± 1.2, BGM, 117.4 ± 1.4 and AGM, 112.6 ± 1.3 mg/dl respectively. FAA reached highest mean IAUC of 4156 ± 208 mg × min/dl, followed by OGM (3835 ± 270 mg × min/dl), BGM (3730 ± 241 mg × min/dl) and AGM (3394 ± 253 mg × min/dl). Among four methods, OGM produced highest mean GI value than FAA (87 ± 5) than FAA, followed by BGM and AGM (77 ± 1, 68 ± 4 and 63 ± 5, p<0.05). The results suggested that the AGM, BGM and OGM are more variable methods to determine IAUC, GI and rank GI value of food than FAA. The present result does not necessarily apply to other glucose meters. The performance of glucose meter to determine GI value of food should be evaluated and calibrated before use

A Proposed Framework for Influencing Factors of Partnership in E-Taiwan Collaborative Commerce

This paper attempts to integrate concepts of a collaborative commerce and inter-organizational relationship to build a framework for influencing factors of e-Taiwan collaborative commerce partnership and empirically explore it. The importance for five dimensions of the Research Model based on seven top representatives of interviewed six Taiwanese companies engaged in E-Taiwan is summarized. Statistical analysis is used to decide which factors are vital for the success in three phases of partnership in e-Taiwan. Data are collected through a survey of organizations that are actively involved in the planning or operation of E-Taiwan collaborative commerce. The result has been shown the influencing factors are not the same in three phases of partnership in this collaborative commerce. It implies that to manage a collaborative commerce must have different strategies to select, develop, and maintain participants

High levels of serum macrophage migration inhibitory factor and interleukin 10 are associated with a rapidly fatal outcome in patients with severe sepsis

SummaryObjectivesThe aim of this study was to delineate the association between high macrophage migration inhibitory factor (MIF) and interleukin 10 (IL-10) levels in the early phase of sepsis and rapidly fatal outcome.MethodsOne hundred and fifty-three adult subjects with the main diagnosis of severe sepsis (including septic shock) admitted directly from the emergency department of two tertiary medical centers and one regional teaching hospital between January 2009 and December 2011, were included prospectively. MIF and IL-10 levels were measured and outcomes were analyzed by Cox regression analysis according to the following outcomes: rapidly fatal outcome (RFO, death within 48h), late fatal outcome (LFO, death between 48h and 28 days), and survival at 28 days.ResultsAmong the three outcome groups, IL-10 levels were significantly higher in the RFO group (p < 0.001) and no significant differences were seen between the LFO and survivor groups. After Cox regression analysis, each incremental elevation of 1000 pg/ml in both IL-10 and MIF was independently associated with RFO in patients with severe sepsis. Each incremental elevation of 1000 pg/ml in IL-10 increased the RFO risk by a factor of 1.312 (95% confidence interval 1.094–1.575; p=0.003); this was the most significant factor leading to RFO in patients with severe sepsis.ConclusionsPatients with RFO exhibited simultaneously high MIF and IL-10 levels in the early phase of severe sepsis. Incremental increases in both IL-10 and MIF levels were associated with RFO in this patient group, and of the two, IL-10 was the most significant factor linked to RFO

Reduced Health-Related Quality of Life in Elders with Frailty: A Cross-Sectional Study of Community-Dwelling Elders in Taiwan

PURPOSE: Exploring the domains and degrees of health-related quality of life (HRQOL) that are affected by the frailty of elders will help clinicians understand the impact of frailty. This association has not been investigated in community-dwelling elders. Therefore, we examined the domains and degree of HRQOL of elders with frailty in the community in Taiwan. METHODS: A total of 933 subjects aged 65 years and over were recruited in 2009 from a metropolitan city in Taiwan. Using an adoption of the Fried criteria, frailty was defined by five components: shrinking, weakness, poor endurance and energy, slowness, and low physical activity level. HRQOL was assessed by the short form 36 (SF-36). The multiple linear regression model was used to test the independent effects of frailty on HRQOL. RESULTS: After multivariate adjustment, elders without frailty reported significantly better health than did the pre-frail and frail elders on all scales, and the pre-frail elders reported better health than did the frail elders for all scales except the scales of role limitation due to physical and emotional problems and the Mental Component Summary (MCS). The significantly negative differences between frail and robust elders ranged from 3.58 points for the MCS to 22.92 points for the physical functioning scale. The magnitude of the effects of frail components was largest for poor endurance and energy, and next was for slowness. The percentages of the variations of these 10 scales explained by all factors in the models ranged from 11.1% (scale of role limitation due to emotional problems) to 49.1% (scale of bodily pain). CONCLUSIONS: Our study demonstrates that the disabilities in physical health inherent in frailty are linked to a reduction in HRQOL. Such an association between clinical measures and a generic measure of the HRQOL may offer clinicians new information to understand frailty and to conceptualize it within the broader context of disability

Current trends in drug metabolism and pharmacokinetics.

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug-drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice

Safety and efficacy of intracoronary artery administration of human bone marrow-derived mesenchymal stem cells in STEMI of Lee-Sung pigs—A preclinical study for supporting the feasibility of the OmniMSC-AMI phase I clinical trial

BackgroundThis study tested whether early left intracoronary arterial (LAD) administration of human bone marrow-derived mesenchymal stem cells (hBMMSCs, called OmniMSCs) in acute ST-segment elevation myocardial infarction (STEMI) of Lee-Sung pigs induced by 90 min balloon-occluded LAD was safe and effective.Methods and resultsYoung male Lee-Sung pigs were categorized into SC (sham-operated control, n = 3), AMI-B (STEMI + buffer/21 cc/administered at 90 min after STEMI, n = 6), and AMI-M [acute myocardial infarction (AMI) + hBMMSCs/1.5 × 107/administered at 90 min after STEMI, n = 6] groups. By 2 and 5 months after STEMI, the cardiac magnetic resonance imaging demonstrated that the muscle scar score (MSS) and abnormal cardiac muscle exercise score in the infarct region were significantly increased in the AMI-B than in the SC group that were significantly reversed in the AMI-M group, whereas the left ventricular ejection function by each month (from 1 to 5) displayed an opposite pattern of MSS among the groups (all p &lt; 0.001). By 5 months, histopathological findings of infarct and fibrosis areas and isolectin-B4 exhibited an identical pattern, whereas the cellular expressions of troponin-I/troponin-T/von Willebrand factor exhibited an opposite pattern of MSS among the groups (all p &lt; 0.001). The ST-segment resolution (&gt;80%) was significantly earlier (estimated after 6-h AMI) in the AMI-M group than in the AMI-B group (p &lt; 0.001). The protein expressions of inflammation (IL-1β/TNF-α/NF-κB)/oxidative stress (NOX-1/NOX-2/oxidized protein)/apoptosis (cleaved caspase-3/cleaved PARP)/DNA damage (γ-H2AX) displayed an identical pattern to MSS among the groups, whereas the protein expressions of angiogenesis factors (SDF-1α/VEGF) were significantly and progressively increased from SC, AMI-B, to AMI-M groups (all p &lt; 0.001).ConclusionEarly intra-LAD transfusion of OmniMSC treatment effectively reduced the infarct size and preserved LV function in porcine STEMI

Pilot Scale Production of Highly Efficacious and Stable Enterovirus 71 Vaccine Candidates

BACKGROUND: Enterovirus 71 (EV71) has caused several epidemics of hand, foot and mouth diseases (HFMD) in Asia and now is being recognized as an important neurotropic virus. Effective medications and prophylactic vaccine against EV71 infection are urgently needed. Based on the success of inactivated poliovirus vaccine, a prototype chemically inactivated EV71 vaccine candidate has been developed and currently in human phase 1 clinical trial. PRINCIPAL FINDING: In this report, we present the development of a serum-free cell-based EV71 vaccine. The optimization at each step of the manufacturing process was investigated, characterized and quantified. In the up-stream process development, different commercially available cell culture media either containing serum or serum-free was screened for cell growth and virus yield using the roller-bottle technology. VP-SFM serum-free medium was selected based on the Vero cell growth profile and EV71 virus production. After the up-stream processes (virus harvest, diafiltration and concentration), a combination of gel-filtration liquid chromatography and/or sucrose-gradient ultracentrifugation down-stream purification processes were investigated at a pilot scale of 40 liters each. Although the combination of chromatography and sucrose-gradient ultracentrifugation produced extremely pure EV71 infectious virus particles, the overall yield of vaccine was 7-10% as determined by a VP2-based quantitative ELISA. Using chromatography as the downstream purification, the virus yield was 30-43%. To retain the integrity of virus neutralization epitopes and the stability of the vaccine product, the best virus inactivation was found to be 0.025% formalin-treatment at 37 °C for 3 to 6 days. Furthermore, the formalin-inactivated virion vaccine candidate was found to be stable for >18 months at 4 °C and a microgram of viral proteins formulated with alum adjuvant could induce strong virus-neutralizing antibody responses in mice, rats, rabbits, and non-human primates. CONCLUSION: These results provide valuable information supporting the current cell-based serum-free EV71 vaccine candidate going into human Phase I clinical trials

Six-membered ring systems: with O and/or S atoms

A large variety of publications involving O- and S-6-membered ring systems have appeared in 2017. The importance of these heterocyclic compounds is highlighted by the huge number of publications on the total synthesis of natural oxygen derivatives and of other communications dedicated to synthetic derivatives. Reviews on stereoselective organocatalytic synthesis of tetrahydropyrans (17EJO4666), of tetrahydropyrans and their application in total synthesis of natural products (17CSR1661), on the synthesis of the less thermodynamically stable 2,6-trans-tetrahydropyrans (17S4899), on enantioselective synthesis of polyfunctionalized pyran and chromene derivatives (17TA1462), and on enantioselective and racemic total synthesis of camptothecins, including the formation of their pyran-2-one ring (17SL1134), have appeared. Advances in the transition metal-catalyzed synthesis of pyran-2/4-ones (17TL263), N-heterocyclic carbene (NHC)-catalyzed achiral synthesis of pyran-2-one, coumarin and (thio)chromone derivatives (17OBC4731), on the synthesis and transformation of 2H-pyran-2-ones (17T2529) and 2-styrylchromones (17EJO3115) into other heterocyclic compounds, have been surveyed. The strategies to build up the tetrahydropyranyl core of brevisamide (17H(95)81) and the reactions of ketyl radicals, generated from carbonyl derivatives under transition-metal photoredox-catalyzed conditions, leading to isochromen- and chroman-type compounds (17CC13093) were disclosed. Developments in the synthesis of pentafluorosulfanyl(chromene and coumarin) derivatives (17TL4803), photoswitchable D9-tetrahydrocannabinol derivatives (17JA18206), and aminobenzopyranoxanthenes with nitrogen-containing rings (17JOC13626) have been studied.info:eu-repo/semantics/publishedVersio

The global response: How cities and provinces around the globe tackled Covid-19 outbreaks in 2021

Background: Tackling the spread of COVID-19 remains a crucial part of ending the pandemic. Its highly contagious nature and constant evolution coupled with a relative lack of immunity make the virus difficult to control. For this, various strategies have been proposed and adopted including limiting contact, social isolation, vaccination, contact tracing, etc. However, given the heterogeneity in the enforcement of these strategies and constant fluctuations in the strictness levels of these strategies, it becomes challenging to assess the true impact of these strategies in controlling the spread of COVID-19.Methods: In the present study, we evaluated various transmission control measures that were imposed in 10 global urban cities and provinces in 2021 Bangkok, Gauteng, Ho Chi Minh City, Jakarta, London, Manila City, New Delhi, New York City, Singapore, and Tokyo.Findings: Based on our analysis, we herein propose the population-level Swiss cheese model for the failures and pit-falls in various strategies that each of these cities and provinces had. Furthermore, whilst all the evaluated cities and provinces took a different personalized approach to managing the pandemic, what remained common was dynamic enforcement and monitoring of breaches of each barrier of protection. The measures taken to reinforce the barriers were adjusted continuously based on the evolving epidemiological situation.Interpretation: How an individual city or province handled the pandemic profoundly affected and determined how the entire country handled the pandemic since the chain of transmission needs to be broken at the very grassroot level to achieve nationwide control

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care