Hemoglobin A1c Levels Modify Associations between Dietary Acid Load and Breast Cancer Recurrence.

BackgroundMetabolic acidosis promotes cancer metastasis. No prospective studies have examined the association between dietary acid load and breast cancer recurrence among breast cancer survivors, who are susceptible to metabolic acidosis. Hyperglycemia promotes cancer progression and acid formation; however, researchers have not examined whether hyperglycemia can modify the association between dietary acid load and breast cancer recurrence.MethodsWe studied 3081 early-stage breast cancer survivors enrolled in the Women's Healthy Eating and Living study who provided dietary information through 24-h recalls at baseline and during follow-up and had measurements of hemoglobin A1c (HbA1c) at baseline. We assessed dietary acid load using two common dietary acid load scores, potential renal acid load (PRAL) score and net endogenous acid production (NEAP) score.ResultsAfter an average of 7.3 years of follow-up, dietary acid load was positively associated with recurrence when baseline HbA1c levels were ≥ 5.6% (median level) and ≥5.7% (pre-diabetic cut-point). In the stratum with HbA1c ≥ 5.6%, comparing the highest to the lowest quartile of dietary acid load, the multivariable-adjusted hazard ratio was 2.15 (95% confidence interval [CI] 1.34-3.48) for PRAL and was 2.31 (95% CI 1.42-3.74) for NEAP. No associations were observed in the stratum with HbA1c levels were <5.6%. P-values for interactions were 0.01 for PRAL and 0.05 for NEAP.ConclusionsOur study demonstrated for the first time that even at or above normal to high HbA1c levels, dietary acid load was associated with increased risk of breast cancer recurrence among breast cancer survivors.ImpactsOur study provides strong evidence for developing specific dietary acid load guidelines based on HbA1c levels

Conceptualizing socioscientific decision making from a review of research in science education

Abstract: This article proposes a theoretical framework for conceptualizing socioscientific decision making, reviews current research in this area, and intends to shed some light on the instructional design for the classroom implementation of socioscientific decision making. The framework involves 3 phases: formulate the decision-making space, posit a decision-making strategy, and reflect on the decision-making process. A total of 24 articles that specifically focused on socioscientific decision making were included. They were classified into 2 groups. The first group explored students’ socioscientific decision-making behavior and its relationships with their cognitive conditions. The second examined the effectiveness of the interventions, that is, task conditions. The analysis showed that most of the studies in both groups focused on phase 1 and studied 3 research themes: informal reasoning, evidence-based reasoning, and social interactions. The findings indicated the challenges phases 1 and 2 posed to students, such as prioritizing criteria and employing a suitable decision-making strategy. Two cognitive conditions, scientific knowledge and scientific epistemological beliefs, appeared to have a more direct impact on evidence-based reasoning rather than on informal reasoning. Group 2 studies designed various interventions and looked into divergent socioscientific decision-making performances across 3 phases. The framework helps conceptualize socioscientific decision making in a more structural and holistic way. The content review provides instructional insights for the socioscientific decision-making process and suggests several future research directions

Cytotoxicity in the Age of Nano: The Role of Fourth Period Transition Metal Oxide Nanoparticle Physicochemical Properties

A clear understanding of physicochemical factors governing nanoparticle toxicity is still in its infancy. We used a systematic approach to delineate physicochemical properties of nanoparticles that govern cytotoxicity. The cytotoxicity of fourth period metal oxide nanoparticles (NPs): TiO2, Cr2O3, Mn2O3, Fe2O3, NiO, CuO, and ZnO increases with the atomic number of the transition metal oxide. This trend was not cell-type specific, as observed in non-transformed human lung cells (BEAS-2B) and human bronchoalveolar carcinoma-derived cells (A549). Addition of NPs to the cell culture medium did not significantly alter pH. Physiochemical properties were assessed to discover the determinants of cytotoxicity: (1) point-of-zero charge (PZC) (i.e., isoelectric point) described the surface charge of NPs in cytosolic and lysosomal compartments; (2) relative number of available binding sites on the NP surface quantified by X-ray photoelectron spectroscopy was used to estimate the probability of biomolecular interactions on the particle surface; (3) band-gap energy measurements to predict electron abstraction from NPs which might lead to oxidative stress and subsequent cell death; and (4) ion dissolution. Our results indicate that cytotoxicity is a function of particle surface charge, the relative number of available surface binding sites, and metal ion dissolution from NPs. These findings provide a physicochemical basis for both risk assessment and the design of safer nanomaterials

Assessment of gene-covariate interactions by incorporating covariates into association mapping

The HLA region is considered to be the main genetic risk factor for rheumatoid arthritis. Previous research demonstrated that HLA-DRB1 alleles encoding the shared epitope are specific for disease that is characterized by antibodies to cyclic citrullinated peptides (anti-CCP). In the present study, we incorporated the shared epitope and either anti-CCP antibodies or rheumatoid factor into linkage disequilibrium mapping, to assess the association between the shared epitope or antibodies with the disease gene identified. Incorporating the covariates into the association mapping provides a mechanism 1) to evaluate gene-gene and gene-environment interactions and 2) to dissect the pathways underlying disease induction/progress in quantitative antibodies

Comparison of significance level at the true location using two linkage approaches: LODPAL and GENEFINDER

BACKGROUND: We compare two new software packages for linkage analysis, LODPAL and GENEFINDER. Both allow for covariate adjustment. Replicates 1 to 3 of Genetic Analysis Workshop 13 simulated data sets were used for the analyses. We described the results of searching for evidence of loci contributing to a simulated quantitative trait related to systolic blood pressure (SBP). Individuals with SBP greater than 130 mm Hg were defined as affected individuals, and all others as unaffected. Total cholesterol was treated as a covariate. RESULTS: Using LODPAL, the power of detecting one of the three major genes related to SBP is 44.4% when a LOD score of 1 is used as the cut-off point. The power of GENEFINDER is lower than that of LODPAL. It is 22.2%. CONCLUSIONS: Based on the limited comparison, LODPAL provided the more reasonable power to detect linkage compared to GENEFINDER. After adjusting for the total cholesterol covariate, the current version of both programs appeared to give a high number of false positives

BU10038 as a safe opioid analgesic with fewer side-effects after systemic and intrathecal administration in primates

© 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.Background: The marked increase in mis-use of prescription opioids has greatly affected our society. One potential solution is to develop improved analgesics which have agonist action at both mu opioid peptide (MOP) and nociceptin/orphanin FQ peptide (NOP) receptors. BU10038 is a recently identified bifunctional MOP/NOP partial agonist. The aim of this study was to determine the functional profile of systemic or spinal delivery of BU10038 in primates after acute and chronic administration. Methods: A series of behavioural and physiological assays have been established specifically to reflect the therapeutic (analgesia) and side-effects (abuse potential, respiratory depression, itch, physical dependence, and tolerance) of opioid analgesics in rhesus monkeys. Results: After systemic administration, BU10038 (0.001–0.01 mg kg −1 ) dose-dependently produced long-lasting antinociceptive and antihypersensitive effects. Unlike the MOP agonist oxycodone, BU10038 lacked reinforcing effects (i.e. little or no abuse liability), and BU10038 did not compromise the physiological functions of primates including respiration, cardiovascular activities, and body temperature at antinociceptive doses and a 10–30-fold higher dose (0.01–0.1 mg kg −1 ). After intrathecal administration, BU10038 (3 μg) exerted morphine-comparable antinociception and antihypersensitivity without itch scratching responses. Unlike morphine, BU10038 did not cause the development of physical dependence and tolerance after repeated and chronic administration. Conclusions: These in vivo findings demonstrate the translational potential of bifunctional MOP/NOP receptor agonists such as BU10038 as a safe, non-addictive analgesic with fewer side-effects in primates. This study strongly supports that bifunctional MOP/NOP agonists may provide improved analgesics and an alternative solution for the ongoing prescription opioid crisis.Peer reviewedFinal Published versio