44 research outputs found
New Insights into the Mechanism of Visible Light Photocatalysis
ABSTRACT: In recent years, the area of developing visible-lightactive photocatalysts based on titanium dioxide has been enormously investigated due to its wide range of applications in energy and environment related fields. Various strategies have been designed to efficiently utilize the solar radiation and to enhance the efficiency of photocatalytic processes. Building on the fundamental strategies to improve the visible light activity of TiO2-based photocatalysts, this Perspective aims to give an insight into many contemporary developments in the field of visible-light-active photocatalysis. Various examples of advanced TiO2 composites have been discussed in relation to their visible light induced photoconversion efficiency, dynamics of electron− hole separation, and decomposition of organic and inorganic pollutants, which suggest the critical need for further development of these types of materials for energy conversion and environmental remediation purposes
The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy
Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations.
Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves.
Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p 90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score.
Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care
T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays
Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades
Citizens of Nowhere: longing, belonging and exile among Irish Protestant writers in Britain, c
β-Cyclodextrin Attenuates Perfluorooctanoic Acid Toxicity in the Zebrafish Embryo Model
Perfluorooctanoic acid (PFOA) has been linked to negative health outcomes including cancer, thyroid disease, infertility, and developmental delays. β-Cyclodextrin (β-CD), a cyclic sugar, has been previously shown to form strong host–guest complexes with PFOA, and is proposed as a means of environmental remediation with respect to this widespread contaminant. In the present study, β-CD was directly examined with regards to possible attenuation of the toxicity of PFOA specifically employing the zebrafish (Danio rerio) embryo model. Zebrafish embryos were exposed to various concentrations of PFOA without β-CD, and with equimolar (1:1) and excess (2:1) molar ratios of β-CD to PFOA, and assessed for lethality and developmental toxicity through seven days post-fertilization (dpf). Rapid onset of lethality with limited morphological abnormalities was observed at relatively low concentrations of PFOA (LC50 ≈ 50 ppm), along with effects on morphometric and neurobehavioral parameters in surviving embryos. A highly significant difference (p < 0.0001) was observed between the 2:1 treatment, and both 1:1 and PFOA only treatments, with respect to lethal concentration and apparent neurobehavioral effects, suggesting an effectively reduced toxicity of the fully complexed PFOA. In contrast, however, neither β-CD treatment reduced developmental toxicity with respect to the morphometric endpoint (i.e., interocular distance). Whereas LC50 of PFOA alone did not change over 7 dpf, the 1:1 and 2:1 values decreased slightly over time, suggesting either delayed or alternative toxic effects on later developmental stages at presumptively lowered levels. This study, therefore, indicates β-CD may be an effective agent to reduce toxicity of and mitigate environmental health concerns associated with PFOA, but that further study is required to elucidate the mechanism of complexation as it relates to the attenuation of toxicity
β‑Cyclodextrin Reverses Binding of Perfluorooctanoic Acid to Human Serum Albumin
Perfluorooctanoic
acid (PFOA), a persistent organic pollutant known
to cause adverse health effects, strongly binds to human serum albumin
(HSA). β-Cyclodextrin (β-CD), a nontoxic cyclic sugar,
strongly complexes PFOA in a host–guest complex and has been
proposed for environmental remediation of PFOA. The interactions between
HSA, PFOA, and β-CD were investigated in order to determine
if β-CD can reverse the binding of PFOA to HSA, with potential
therapeutic applications toward exposure to PFOA. <sup>19</sup>F Nuclear
magnetic resonance (NMR), circular dichroism, and fluorescence spectroscopies
were used to study these interactions. Multiple PFOA binding sites
to HSA, one with strong affinity and others with low affinity, are
evident from changes in the fluorescence emission spectra of HSA and
the fluorescence lifetimes of the single Trp residue in HSA with increasing
PFOA concentration. Structural changes in the protein are also evident
from changes in the circular dichroism spectra of HSA upon titration
of PFOA. Addition of β-CD to PFOA and HSA reversed these changes,
indicating that formation of the β-CD:PFOA host–guest
complex is favored even in the presence of HSA. Equimolar β-CD
to PFOA (1:1 β-CD:PFOA ratio) causes dissociation of the weakly
bound PFOA from HSA, whereas excess β-CD relative to PFOA (5:1
β-CD:PFOA ratio) leads to the complete disassociation of the
strongly bound PFOA molecule from HSA. The <sup>19</sup>F NMR studies
further suggest that the 2:1 β-CD:PFOA complex inhibits PFOA
binding to HSA. These data demonstrate that β-CD has potential
to be used in therapeutic applications for PFOA in human blood
<sup>19</sup>F NMR Characterization of the Encapsulation of Emerging Perfluoroethercarboxylic Acids by Cyclodextrins
Legacy perfluoroalkyl
substances (PFASs) are known environmental
pollutants with serious adverse health effects. Perfluoroethercarboxylic
acids (PFECAs), emerging PFASs now being substituted for legacy PFASs,
have recently been detected in the environment. Cyclodextrins (CDs)
have been proposed as agents for the remediation of problematic pollutants,
including legacy PFASs. The current study uses <sup>19</sup>F NMR
spectroscopy to measure the complexation of mono-, di-, and triether
PFECAs by CDs for eventual environmental applications. Eight PFECAs
were characterized by <sup>19</sup>F and <sup>13</sup>C NMR. The change
in chemical shift of individual fluorines upon complexation of CDs
at various stoichiometric ratios was used to determine the host–guest
association constants. All studied PFECAs were most strongly encapsulated
by β-CD, with association constants from 10<sup>2</sup>–10<sup>5</sup> M<sup>–1</sup> depending on chain length and number
of ether functionalities. <sup>19</sup>F–<sup>1</sup>H heteronuclear
Overhauser effect spectroscopy (HOESY) NMR experiments were performed
for the β-CD complexes of two branched monoethers, PFPrOPrA
(“GenX”) and PFDMMOBA, to elucidate the structural details
of the complexes, determine the specific orientation, and position
of β-CD along the PFAS chain, and assess the roles of hydrogen-bonding
and PFECA branching on the host–guest interactions. The results
give new understanding into the fundamental nature of the host–guest
complex between cyclodextrins and perfluorinated surfactants
Synthesis and Antiproliferative Activity of Novel Heterocyclic Indole-Trimethoxyphenyl Conjugates
The synthesis and biological evaluation of a series of novel heterocyclic indole derivatives is described. The consolidation of the combretastatin and bisindolylmaleimide templates towards the inclusion of a novel heterocyclic ring proffered a versatile pharmacophore with which to pursue chemical diversification. Given literature precedent, maleimide was initially investigated in this role and the bioactivity assessed by measurement of NCI-60 cell panel growth. Subsequently, a range of 5-aminopyrazoles was designed and developed to explore the specific effect of heterocycle hydrogen bonding on cell growth. The unique electronic nature of the 5-aminopyrazole moiety allowed for regiospecific monosubstitution on different sites of the ring, such as thiourea substitution at the N(1) position for derivative 45 or trifluoroacetylation on the 5-amino position for 43. Further derivatisation led to the ultimate development of bicyclic pyrazolotriazinedione 41 and pyrimidine 42 systems. The antiproliferative activities of these 3,4-diaryl-5-aminopyrazoles were assessed using the NCI-60 cell screen, disclosing the discovery of distinct selectivity profiles towards a number of cell lines, such as SNB-75 CNS cancer, UO-31 and CAKI-1 renal cancer cells. A series of DNA topological assays discounted the interaction with topoisomerase II as a putative mechanism of action
Kinetic and Mechanistic Evaluation of Inorganic Arsenic Species Adsorption onto Humic Acid Grafted Magnetite Nanoparticles
Humic
acid coated magnetic iron oxide nanoparticles (HA-MNPs) were
synthesized, characterized, and studied for the removal of toxic inorganic
arsenic species from aqueous media. The adsorption of As(III) and
As(V) followed pseudo-second-order kinetics, and the observed data
were accurately modeled employing the Freundlich adsorption isotherm.
Application of the Weber and Morris intraparticle diffusion model
to the observed kinetic data suggests that the adsorption occurs in
three distinct stages, fast, intermediate, and slow steps. We propose
the initial stage is governed by surface association, followed by
intraparticle diffusion of arsenic through the HA matrix and, finally,
chemical reaction or bonding between the arsenic species and HA functionality.
The HA-MNP nanoadsorbent absorbs >95% of the inorganic arsenic
species
with an absorption capacity of 12.2–12.6 mg/g from aqueous
media and is effective under a variety of conditions. Post arsenic
adsorption characterization of the nanoparticles suggests that As(III)
binds with the carboxylate group of HA through a proposed ester type
linkage, while electrophilic reactions can occur between the nucleophilic
functional groups present in HA and the electrophilic arsenic atom
in As(V). The results obtained demonstrated that HA-MNPs are robust
and have promise for effective As(III) and As(V) remediation