A smart chitosan-graphite molecular imprinted composite for the effective trapping and sensing of Dimethyl Methylphosphonate based on changes in resistance.

A molecular imprinted polymer (MIP) fabricated from a chitosan doped with graphite to create a conductive composite (CG-MIC) with the ability to trap and detect dimethyl methylphosphonate (DMMP) through a change in resistance of the material has been successfully manufactured. The GC-MIC presented a maximum trapping capacity of 96 ppm (0.096 mg/g) of DMMP. A similar non-imprinted composite made of chitosan-graphite (CG-NIC) had a surface adsorption of 48 ppm (0.048 mg/g) of DMMP. The manufacturing process was tested for consistency and there were no significant differences in resistance between batches of CG-MIC before (around 450 Ω) and after (around 70 Ω) DMMP extraction, representing a homogeneous manufacturing process. Although Atomic Force Microscopy studies revealed that the graphite was not homogenously distributed throughout the chitosan matrix, the response was consistent. The changes in the concentration of DMMP within the self-sensing material, being proportional to those in gas concentration, could be followed by the changes in resistance. The inclusion of common interferences: Acetic acid, acetone, ethanol, ammonium hydroxide and 2-propanol, equivalent in concentration to the DMMP, caused a change in the resistance of the material but did not substantially affect the specific resistance response of the composite material. Based on this data, the CG-MIC could be used as a smart material with sensing capabilities to monitor trapping levels of DMMP

A review of sensing technologies for gas nerve agents, through the use of agent mimics in the gas phase: future needs

The aim of the work presented in this review is to present a detailed summary of the current sensing technology available within the scientific literature for the detection of nerve agent simulants in the gas phase, focussing on the recognised sarin surrogate: dimethyl methylphonate (DMMP). The use of simulants for the development of sensing technology has been widely established for nerve agents to reduce the potential risk to personnel and to offer a realistic, simple molecule to try and test the technology. The present review compiles a comparison of different sensors and their respective sensing mechanisms. These sensing technologies are then compared to the U.S environmental protection agencies standard for concentration of Sarin at 15 ppb (known lethal dose). Only some work developed using semiconductor detectors present a reliable system able to detect DMMP with low LoD (0.05 ppb), fast response time (0.02 mins) and good recovery times (0.5 min)

Electropolymerization of metallo-octaethylporphyrins: a study to explore their sensing capabilities

The electropolymerization of metallo-octaethylporphyrins (OEP) containing copper, zinc or nickel metal were performed using cyclic voltammetry at three different potential ranges. The electropolymerized porphyrins were characterized by UV-Vis and Raman spectroscopies and the Soret band (393–445 nm) and Raman bands were used to assess the degree of electropolymerization obtained. The application for an analytical use of the modified electrodes to determine phenobarbital in aqueous solution was evaluated. The electropolymerized CuOEP produced at potentials ranging from 0.0 to 2.2 V was the best performer with a limit of detection (LoD) of 10 mg L−1 (43.07 µM), a linear range of 10–150 mg L−1 (43.07 to 646 µM), an average precision of 4.3% (%RSD) and an average % recovery of 101.34%. These results indicate that the CuOEP-modified electrode is suitable for the analysis of phenobarbital in human samples, as the concentration range varies from 10 to 40 mg L−1 (43.07 to 172.27 µM), typically found in antiepileptic treatments, to those at the toxic level (172–258 µM) or lethal levels (345–650 µM)

Analysis of omeprazole and esomeprazole obtained from traditional pharmacies and unlicensed internet websites using Raman spectroscopy, 1H-NMR and chemometric analysis

The relevant therapeutic outcomes obtained with the use of proton pump inhibitors for the treatment of gastric conditions have an important reflection on the prescribing habits of clinicians of primary and secondary care organizations. With the attempt to reduce their financial impact on the health systems, generic medications, obtained both from tradition distribution chain and from parallel import, have represented the main type of proton pump inhibitors used in clinics recently. The effect of parallel import and the use of the internet as an international distribution network significantly facilitates the entry of falsified medicines in the official channels of distribution. Since the interchangeability of different omeprazole preparations has been previously questioned, in this study we used Raman and 1H-NMR to characterise different omeprazole and esomeprazole formulations produced by different manufacturers and obtained from both traditional pharmacies and from unlicensed internet market in order to establish if any differences could be found to substantiate any different clinical performances. A chemometric study of Raman spectra allowed partial separation indicating that there are not sufficient chemical differences for PCA groups to be established using this analytical approach and for these specific medications. On the contrary, NMR investigations allowed the identification of impurities in internet samples, not detected by the Raman analyses, making this technique a valid candidate analytical tool to adopt for the investigation of falsified medicines

Computational Design of a Molecularly Imprinted Polymer for the Biomonitoring of the Organophosphorous Metabolite Chlorferron

: Coumaphos is an organophosphorus compound used as insecticide and frequently used by beekeepers for the management of parasitic mites. The most important metabolite, chlorferron (CFN), has been identified in biological samples and foodstuff. The need to quickly identify the presence of typical metabolites, as an indication of interaction with coumaphos has driven the need to produce a highly sensitive electrochemical method for chlorferron analysis, based on molecularly imprinting polymers (MIP) technology. It showed irreversible behaviour with mixed diffusion/adsorption�controlled reactions at the electrode surface. A monoelectronic mechanism of reaction for oxidation has also been suggested. The linear range observed was from 0.158 to 75 µM. Median precision in terms of %RSD around 3% was also observed. For DPV, the limit of detection (LOD) and the limit of quantitation (LOQ) for the CFN-MIP were 0.158 µM and 0.48 µM, respectively. The obtained median % recovery was around 98%. The results were also validated to reference values obtained using GC-MS. Urine and human synthetic plasma spiked with CFN were used to demonstrate the usability of the method in biological samples, showing the potential for biomonitoring. The developed imprinted sensor showed maximum signal change less than 16.8% when related metabolites or pesticide were added to the mix, suggesting high selectivity of the MIP sensor toward CFN molecules. The results from in vitro metabolism of CMP analysed also demonstrates the potential for detection and quantification of CFN in environmental samples. The newly developed CFN-MIP sensor offers similar LoDs than chromatographic methods with shorter analysis time

A molecular imprinted polymer sensor for biomonitoring of fenamiphos pesticide metabolite fenamiphos sulfoxide.

A new electrochemical method for the identification and quantification of Fenamiphos pesticide’s major metabolite in biological samples –Fenamiphos Sulphoxide (FNX) was developed. Computational calculations, Density Functional Theory (DFT) and semi-empirical models (PM3) were performed to determine the best monomer, pyrrole, and a ratio of 1:5 (template: monomer) was chosen for the fabrication of the FNX-MIP sensor obtained by electropolymerization. The FNX�MIP sensor responded well to increasing FNX concentrations (range of 1-30 µM). Limit of detection and quantification (LOD=0.183 µM, LOQ=0.601 µM), respectively, selectivity, and repeatability were also investigated for the developed method. The obtained percentage of recovery showed good agreement compared to reference values obtained from GC-MS, which was used as a reference method. The FXN-MIP sensor proved selective in the presence of potential interferents. The developed sensor was successfully applied for the determination of FNX in spiked plasma and urine matrixes with acceptable recovery rates. The proposed method also proved successful in detecting FNX prepared from the in vitro metabolism of FNP using liver microsomes to metabolize it

Identification of lptA, lpxE, and lpxO, Three Genes Involved in the Remodeling of Brucella Cell Envelope.

The brucellae are facultative intracellular bacteria that cause a worldwide extended zoonosis. One of the pathogenicity mechanisms of these bacteria is their ability to avoid rapid recognition by innate immunity because of a reduction of the pathogen-associated molecular pattern (PAMP) of the lipopolysaccharide (LPS), free-lipids, and other envelope molecules. We investigated the Brucella homologs of lptA, lpxE, and lpxO, three genes that in some pathogens encode enzymes that mask the LPS PAMP by upsetting the core-lipid A charge/hydrophobic balance. Brucella lptA, which encodes a putative ethanolamine transferase, carries a frame-shift in B. abortus but not in other Brucella spp. and phylogenetic neighbors like the opportunistic pathogen Ochrobactrum anthropi. Consistent with the genomic evidence, a B. melitensis lptA mutant lacked lipid A-linked ethanolamine and displayed increased sensitivity to polymyxin B (a surrogate of innate immunity bactericidal peptides), while B. abortus carrying B. melitensis lptA displayed increased resistance. Brucella lpxE encodes a putative phosphatase acting on lipid A or on a free-lipid that is highly conserved in all brucellae and O. anthropi. Although we found no evidence of lipid A dephosphorylation, a B. abortus lpxE mutant showed increased polymyxin B sensitivity, suggesting the existence of a hitherto unidentified free-lipid involved in bactericidal peptide resistance. Gene lpxO putatively encoding an acyl hydroxylase carries a frame-shift in all brucellae except B. microti and is intact in O. anthropi. Free-lipid analysis revealed that lpxO corresponded to olsC, the gene coding for the ornithine lipid (OL) acyl hydroxylase active in O. anthropi and B. microti, while B. abortus carrying the olsC of O. anthropi and B. microti synthesized hydroxylated OLs. Interestingly, mutants in lptA, lpxE, or olsC were not attenuated in dendritic cells or mice. This lack of an obvious effect on virulence together with the presence of the intact homolog genes in O. anthropi and B. microti but not in other brucellae suggests that LptA, LpxE, or OL β-hydroxylase do not significantly alter the PAMP properties of Brucella LPS and free-lipids and are therefore not positively selected during the adaptation to intracellular life

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy

Rhinitis associated with asthma is distinct from rhinitis alone: The ARIA-MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitization patterns (mono- or pauci-sensitization versus polysensitization), (iii) severity of symptoms, and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and autoimmune diseases

HE-LHC: The High-Energy Large Hadron Collider: Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries