Edible Osmanthus fragrans flowers: aroma and functional components, beneficial functions, and applications.

Osmanthus fragrans (O. fragrans) has been cultivated in China for over 2,500 years as a traditional fragrant plant. Recently, O. fragrans has drawn increasing attention due to its unique aroma and potential health benefits. In this review, the aroma and functional components of O. fragrans are summarized, and their biosynthetic mechanism is discussed. The beneficial functions and related molecular mechanism of O. fragrans extract are then highlighted. Finally, potential applications of O. fragrans are summarized, and future perspectives are proposed and discussed. According to the current research, O. fragrans extracts and components have great potential to be developed into value-added functional ingredients with preventive effects on certain chronic diseases. However, it is crucial to develop efficient, large-scale, and commercially viable extraction methods to obtain the bioactive components from O. fragrans. Furthermore, more clinical studies are highly needed to explore the beneficial functions of O. fragrans and guide its development into functional food products.

A multicomponent index method to evaluate the relationship between urban environment and CHD prevalence.

Cardiovascular disease (CVD) is the leading cause of death globally, coronary heart disease (CHD) is the main category of it. It has been shown that the urban built environment affects the occurrence of CHD, but most focus on single environmental factors. This study developed two multicomponent Urban Heart Health Environment (UHHE) Indexes (unweighted index and weighted index), which were based on the four main behavioral risk factors for CHD (unhealthy diet, lack of physical activity, smoking, and drinking). And we examined the relationship between the indexes and the prevalence of CHD. The prevalence calculation is based on the database of F Hospital patients, who have had coronary stent implantation (CSI). Furthermore, these single-center data were corrected to reduce underestimation of prevalence. We performed global (Ordinal Least Square) and local (Geographically Weighed Regression) regression analyses to assess the relationship between the two UHHE indexes and CHD prevalence. Both indexes showed a significant negative relationship with CHD prevalence. In its spatial relationship, a non-stationary was discovered. The UHHE indexes may help identify and prioritize geographical areas for CHD prevention and may be beneficial to urban design in China.

Optimal individualized decision rules from a multi-arm trial: A comparison of methods and an application to tailoring inter-donation intervals among blood donors in the UK.

There is a growing interest in precision medicine where individual heterogeneity is incorporated into decision-making and treatments are tailored to individuals to provide better healthcare. One important aspect of precision medicine is the estimation of the optimal individualized treatment rule (ITR) that optimizes the expected outcome. Most methods developed for this purpose are restricted to the setting with two treatments, while clinical studies with more than two treatments are common in practice. In this work, we summarize methods to estimate the optimal ITR in the multi-arm setting and compare their performance in large-scale clinical trials via simulation studies. We then illustrate their utilities with a case study using the data from the INTERVAL trial, which randomly assigned over 20,000 male blood donors from England to one of the three inter-donation intervals (12-week, 10-week, and eight-week) over two years. We estimate the optimal individualized donation strategies under three different objectives. Our findings are fairly consistent across five different approaches that are applied: when we target the maximization of the total units of blood collected, almost all donors are assigned to the eight-week inter-donation interval, whereas if we aim at minimizing the low hemoglobin deferral rates, almost all donors are assigned to donate every 12 weeks. However, when the goal is to maximize the utility score that "discounts" the total units of blood collected by the incidences of low hemoglobin deferrals, we observe some heterogeneity in the optimal inter-donation interval across donors and the optimal donor assignment strategy is highly dependent on the trade-off parameter in the utility function.

Deltamethrin promotes adipogenesis via AMPKα and ER stress-mediated pathway in 3T3- L1 adipocytes and Caenorhabditis elegans.

Previous research has shown that deltamethrin, a Type-II pyrethroid, increases fat accumulation in adipocytes and Caenorhabditis elegans. The underlying mechanisms on how deltamethrin promotes fat accumulation, however, are unknown. The aim of the current study was therefore to determine the possible mechanisms through which deltamethrin increases fat accumulation in mouse 3T3-L1 adipocytes and C. elegans. Deltamethrin (10 µM) significantly increased fat accumulation, and the expression of adipogenic regulators, such as CCAAT/enhancer-binding protein (C/EBPα) and fatty acid synthase (FAS). Deltamethrin significantly decreased the phosphorylation of AMP-activated kinase α (AMPKα), while it increased protein expression of endoplasmic reticulum (ER) stress markers in 3T3-L1 adipocytes and C. elegans. The activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) or the inhibition of ER stress with 4-phenylbutyrate (4-PBA) abolished the effects of deltamethrin on adipogenesis. Further study reveals that 4-PBA recovered the decreased AMPK phosphorylation induced by deltamethrin. These results suggest that deltamethrin promotes adipogenesis through an ER stress-AMPKα mediated pathway.

Cross-sectional human immunodeficiency virus incidence estimation accounting for heterogeneity across communities.

Accurate estimation of human immunodeficiency virus (HIV) incidence rates is crucial for the monitoring of HIV epidemics, the evaluation of prevention programs, and the design of prevention studies. Traditional cohort approaches to measure HIV incidence require repeatedly testing large cohorts of HIV-uninfected individuals with an HIV diagnostic test (eg, enzyme-linked immunosorbent assay) for long periods of time to identify new infections, which can be prohibitively costly, time-consuming, and subject to loss to follow-up. Cross-sectional approaches based on the usual HIV diagnostic test and biomarkers of recent infection offer important advantages over standard cohort approaches, in terms of time, cost, and attrition. Cross-sectional samples usually consist of individuals from different communities. However, small sample sizes limit the ability to estimate community-specific incidence and existing methods typically ignore heterogeneity in incidence across communities. We propose a permutation test for the null hypothesis of no heterogeneity in incidence rates across communities, develop a random-effects model to account for this heterogeneity and to estimate community-specific incidence, and provide one way to estimate the coefficient of variation. We evaluate the performance of the proposed methods through simulation studies and apply them to the data from the National Institute of Mental Health Project ACCEPT, a phase 3 randomized controlled HIV prevention trial in Sub-Saharan Africa, to estimate the overall and community-specific HIV incidence rates.

p-Coumaric acid improves oxidative and osmosis stress responses in Caenorhabditis elegans.

BACKGROUND: Stress-response pathways in Caenorhabditis elegans (C. elegans) were found to be closely related to human diseases and aging. Research on stress responses in C. elegans can therefore significantly facilitate understanding of related human diseases. p-Coumaric acid is present in peanuts, carrots, and garlic, and exerts many biological effects, however, its responses to various environmental stressors remain unknown. Thus, in the current study, we employed C. elegans as the in vivo animal model to examine the function of p-coumaric acid under various stressed conditions. RESULTS: Treatment of C. elegans with p-coumaric acid resulted in a significant reduction in the intercellular reactive oxygen species levels, which suggests the in vivo antioxidant capacity of p-coumaric acid. Moreover, p-coumaric acid significantly increased the worms' survival under oxidative and osmosis stressed conditions but had no effect under normal or heat-stressed conditions. The increased oxidative resistance induced by p-coumaric acid was mediated by skn-1, an ortholog of the Nrf2 (nuclear factor erythroid 2-related factor 2) transcriptional factor. Downregulation of the osmosis regulatory gene, osr-1, might contribute to p-coumaric acids' effect on increased resistance to high osmolarity. CONCLUSION: Taken together, our results suggest that p-coumaric acid, an antioxidant agent, ameliorated oxidative and osmosis stresses in C. elegans. © 2018 Society of Chemical Industry.

Does Extracorporeal Membrane Oxygenation Improve Survival in Pediatric Acute Respiratory Failure?

RATIONALE: Extracorporeal membrane oxygenation (ECMO) has supported gas exchange in children with severe respiratory failure for more than 40 years, without ECMO efficacy studies. OBJECTIVES: To compare the mortality and functional status of children with severe acute respiratory failure supported with and without ECMO. METHODS: This cohort study compared ECMO-supported children to pair-matched non-ECMO-supported control subjects with severe acute respiratory distress syndrome (ARDS). Both individual case matching and propensity score matching were used. The study sample was selected from children enrolled in the cluster-randomized RESTORE (Randomized Evaluation of Sedation Titration for Respiratory Failure) clinical trial. Detailed demographic and daily physiologic data were used to match patients. The primary endpoint was in-hospital mortality. Secondary outcomes included hospital-free days, ventilator-free days, and change in functional status at hospital discharge. MEASUREMENTS AND MAIN RESULTS: Of 2,449 children in the RESTORE trial, 879 (35.9%) non-ECMO-supported patients with severe ARDS were eligible to match to 61 (2.5%) ECMO-supported children. When individual case matching was used (60 matched pairs), the in-hospital mortality rate at 90 days was 25% (15 of 60) for both the ECMO-supported and non-ECMO-supported children (P > 0.99). With propensity score matching (61 matched pairs), the ECMO-supported in-hospital mortality rate was 15 of 61 (25%), and the non-ECMO-supported hospital mortality rate was 18 of 61 (30%) (P = 0.70). There was no difference between ECMO-supported and non-ECMO-supported patients in any secondary outcomes. CONCLUSIONS: In children with severe ARDS, our results do not demonstrate that ECMO-supported children have superior outcomes compared with non-ECMO-supported children. Definitive answers will require a rigorous multisite randomized controlled trial.

Application of Caenorhabditis elegans for Research on Endoplasmic Reticulum Stress.

Caenorhabditis elegans is a versatile model organism that has been applied to research involving obesity, aging, and neurodegenerative diseases. C. elegans has many advantages over traditional animal models, including ease of handling, a short lifespan, a fully sequenced genome, ease of genetic manipulation, and a high similarity to human disease-related genes. With established C. elegans models of human disease, C. elegans provides a great platform for studying disease pathologies, including endoplasmic reticulum (ER) stress, which is characterized by the accumulation of unfolded and misfolded proteins involved in the pathologies of many diseases. ER stress can lead to activation of the unfolded and misfolded protein response, a mechanism that attenuates ER stress and recovers ER homeostasis. The current review gives an introduction to C. elegans and ER stress, along with the pathological role of ER stress in disease and the application of worm models in ER stress-related research.