Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BackgroundExisting evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients.Patients and methodsChemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain.ResultsNinety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022).ConclusionsWhile elevated concentrations of IL-6 and IL-1β were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes

Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Effect of shoot parameters on cracking in vegetated soil

The relationship of shoot parameters, which play a major role in transpiration, with the cracking of soil has rarely been investigated. Such relation helps to analyse water use efficiency accurately. This study investigated the effect of vegetation (cowpea) age on crack formation and explored any correlation between age and cracking. The age of vegetation was expressed in the form of shoot parameters (shoot length (SL) and leaf area index (LAI)). Crack formation was expressed in the form of crack intensity factor (CIF). Ten experimental test pots were used to observe crack formation on vegetated and bare soil in a greenhouse. Image analysis in the experimental pots revealed that under drying–wetting cycles, the CIF of vegetated soil increased compared with that of bare soil. There was an evident increase in CIF with SL growth, up to a threshold length (400 mm), where lateral branch growth starts forming. There was no observable increase in CIF, with further SL growth (with negligible lateral branch formation). CIF increased with LAI up to a certain threshold value (0·56), after which the CIF was relatively the same. Two correlations have been identified for shoot parameters (SL, LAI) with the CIF for the selected species

Identification of an INa-dependent and Ito-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient

Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS

Electrospun poly(vinyl alcohol) nanofibers: effects of degree of hydrolysis and enhanced water stability

ArticlePOLYMER JOURNAL. 42(3):273-276 (2010)journal articl

Graphene Photonics and Optoelectronics

The richness of optical and electronic properties of graphene attracts enormous interest. Graphene has high mobility and optical transparency, in addition to flexibility, robustness and environmental stability. So far, the main focus has been on fundamental physics and electronic devices. However, we believe its true potential to be in photonics and optoelectronics, where the combination of its unique optical and electronic properties can be fully exploited, even in the absence of a bandgap, and the linear dispersion of the Dirac electrons enables ultra-wide-band tunability. The rise of graphene in photonics and optoelectronics is shown by several recent results, ranging from solar cells and light emitting devices, to touch screens, photodetectors and ultrafast lasers. Here we review the state of the art in this emerging field.Comment: Review Nature Photonics, in pres

Coordinated Expression Domains in Mammalian Genomes

Gene order in eukaryotic genomes is not random. Genes showing similar expression (coexpression) patterns are often clustered along the genome. The goal of this study is to characterize coexpression clustering in mammalian genomes and to investigate the underlying mechanisms.We detect clustering of coexpressed genes across multiple scales, from neighboring genes to chromosomal domains that span tens of megabases and, in some cases, entire chromosomes. Coexpression domains may be positively or negatively correlated with other domains, within and between chromosomes. We find that long-range expression domains are associated with gene density, which in turn is related to physical organization of the chromosomes within the nucleus. We show that gene expression changes between healthy and diseased tissue samples occur in a gene density-dependent manner.We demonstrate that coexpression domains exist across multiple scales. We identify potential mechanisms for short-range as well as long-range coexpression domains. We provide evidence that the three-dimensional architecture of the chromosomes may underlie long-range coexpression domains. Chromosome territory reorganization may play a role in common human diseases such as Alzheimer's disease and psoriasis

Single Crystalline Cadmium Sulfide Nanowires with Branched Structure

In this article, we report the synthesis of branched single crystal CdS nanowires. This branched CdS nanostructure is prepared by a simple surfactant-directing method, which is of particular interest as it uses readily available reagents and provides a convenient route to high-yield single crystal nanowires but with branched shape. These branched nanowires have an average diameter of about 40 nm and length up to several micrometers. A possible mechanism has been proposed and the addition of surfactant dodecylthiol into the two mixed-solvents would play an importance effect on the structure of the product. Based on the mechanism, by controlling the synthesis conditions, such as the ratios between the surfactant, inorganic solvent, and organic solvent, other kinds of nanostructures based on CdS nanowires were also prepared. Photoluminescence (PL) measurement reveals that the branched CdS nanowires have a strong emission at about 700 nm which might be due to its special structure