Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries; it affects primarily older persons, with a median age at diagnosis of 72 years. Chlorambucil has been a standard first-line therapy in CLL, especially for older patients or those with coexisting…

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Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia

The landscape of treatment for relapsed chronic lymphocytic leukemia (CLL) has recently changed with the introduction of agents that inhibit intracellular B-cell receptor signaling. Ibrutinib monotherapy and idelalisib in combination with rituximab induce responses in the majority of patients in…

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Off to the Right Start: Well-Child Visit Attendance Among Health Center Users

This study examines correlates of past-year well-child visit attendance, reasons for choosing to receive care at a health center, and patient experience among pediatric federally qualified health center users.

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Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome

Randomized trials involving patients with new or established type 2 diabetes have shown that improved glucose control reduces the risk of microvascular complications, with modest cardiovascular benefits suggested by meta-analyses and extended follow-up of clinical trials. However, various studies…

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On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection

The prevention of infection with human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) remains a major public health challenge. Owing to the lack of an effective HIV vaccine, consistent condom use remains the cornerstone of prevention, but biomedical interventions such as male circumcision…

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Intensive Supportive Care plus Immunosuppression in IgA Nephropathy

IgA nephropathy is the most common form of glomerulonephritis. Several findings support the use of immunosuppressive therapy to target mesangial IgA deposits and circulating IgA autoantibodies. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines regarding IgA nephropathy recommend…

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A Randomized Trial of Progesterone in Women with Recurrent Miscarriages

Recurrent miscarriage, defined as the loss of three or more pregnancies, affects approximately 1% of couples who attempt to have a child. Even after comprehensive investigations, a cause for recurrent miscarriage is identified in less than half of these couples. Unexplained recurrent miscarriage is…

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Insertion of an Intracranial-Pressure Monitor.

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Detection and Recovery of Palladium, Gold and Cobalt Metals from the Urban Mine Using Novel Sensors/Adsorbents Designated with Nanoscale Wagon-wheel-shaped Pores

Because of the importance and extensive use of palladium, gold and cobalt metals in high-technology equipment, their recovery and recycling constitute an important industrial challenge. The metal recovery system described herein is a simple, low-cost means for the effective detection, removal, and recovery of these metals from the urban mine.

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Mechanism of neem limonoids-induced cell death in cancer: Role of oxidative phosphorylation

Publication date: January 2016
Source:Free Radical Biology and Medicine, Volume 90
Author(s): Neelu Yadav, Sandeep Kumar, Rahul Kumar, Pragya Srivastava, Leimin Sun, Peter Rapali, Timothy Marlowe, Andrea Schneider, Joseph R. Inigo, Jordan O'Malley, Ramesh Londonkar, Raghu Gogada, Ajay K. Chaudhary, Nagendra Yadava, Dhyan Chandra
We have previously reported that neem limonoids (neem) induce multiple cancer cell death pathways. Here we dissect the underlying mechanisms of neem-induced apoptotic cell death in cancer. We observed that neem-induced caspase activation does not require Bax/Bak channel-mediated mitochondrial outer membrane permeabilization, permeability transition pore, and mitochondrial fragmentation. Neem enhanced mitochondrial DNA and mitochondrial biomass. While oxidative phosphorylation (OXPHOS) Complex-I activity was decreased, the activities of other OXPHOS complexes including Complex-II and -IV were unaltered. Increased reactive oxygen species (ROS) levels were associated with an increase in mitochondrial biomass and apoptosis upon neem exposure. Complex-I deficiency due to the loss of Ndufa1-encoded MWFE protein inhibited neem-induced caspase activation and apoptosis, but cell death induction was enhanced. Complex II-deficiency due to the loss of succinate dehydrogenase complex subunit C (SDHC) robustly decreased caspase activation, apoptosis, and cell death. Additionally, the ablation of Complexes-I, -III, -IV, and -V together did not inhibit caspase activation. Together, we demonstrate that neem limonoids target OXPHOS system to induce cancer cell death, which does not require upregulation or activation of proapoptotic Bcl-2 family proteins.



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Preparation of polydopamine-coated magnetic nanoparticles for dispersive solid-phase extraction of water-soluble synthetic colorants in beverage samples with HPLC analysis

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Weibo Chai, Huijuan Wang, Ying Zhang, Guosheng Ding
A facile and sensitive dispersive solid-phase extraction (D-SPE) method for the extraction and enrichment of four representative synthetic colorants prior to high performance liquid chromatography analysis was introduced. As highly efficient adsorbents, polydopamine-coated Fe3O4 nanoparticles (Fe3O4@PDA NPs) were prepared by a simple and green procedure. Several factors affecting the extraction efficiency, mainly including the polymerization time of dopamine, pH of the sample solution, the amount of adsorbent, extraction time and the desorption conditions, were systematically studied. Under the optimized conditions, the enrichment factors for the four colorants were both higher than 176. The limits of detection (LODs) for the established d-SPE-HPLC method were found to be 0.20–0.25μgL⁻¹, which were lower than most chromatographic methods previously reported for synthetic colorant analysis. When used for quantitative analysis, wide linearity ranges (1–500μgL⁻¹ for amaranth and Ponceau 4R, and 0.80–500μgL⁻¹ for sunset yellow and allure red) were achieved with good correlation (R²≥0.9995). The developed method was also successfully applied to the analysis of colorants in beverage samples with satisfactory results, demonstrating its reliability and feasibility in real sample analysis.

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Voltammetric detection of sequence-selective DNA hybridization related to Toxoplasma gondii in PCR amplicons

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Gultekin Gokce, Arzum Erdem, Cagdas Ceylan, Muslum Akgöz
This work describes the single-use electrochemical DNA biosensor technology developed for voltammetric detection of sequence selective DNA hybridization related to important human and veterinary pathogen; Toxoplasma gondii. In the principle of electrochemical label-free detection assay, the duplex of DNA hybrid formation was detected by measuring guanine oxidation signal occured in the presence of DNA hybridization. The biosensor design consisted of the immobilization of an inosine-modified (guanine-free) probe onto the surface of pencil graphite electrode (PGE), and the detection of the duplex formation in connection with the differential pulse voltammetry(DPV) by measuring the guanine signal. Toxoplasma gondii capture probe was firstly immobilized onto the surface of the activated PGE by wet adsorption. The extent of hybridization at PGE surface between the probe and the target was then determined by measuring the guanine signal observed at +1.0V. The electrochemical monitoring of optimum DNA hybridization has been performed in the target concentration of 40µg/mL in 50min of hybridization time. The specificity of the electrochemical biosensor was then tested using non-complementary, or mismatch short DNA sequences. Under the optimum conditions, the guanine oxidation signal indicating full hybridization was measured in various target concentration from 0.5 to 25µg/mL and a detection limit was found to be 1.78µg/mL. This single-use biosensor platform was successfully applied for the voltammetric detection of DNA hybridization related to Toxoplasma gondii in PCR amplicons.

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Separation of curcuminoids using ionic liquid based aqueous two-phase system coupled with in situ dispersive liquid–liquid microextraction

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Yang Shu, Mingcen Gao, Xueying Wang, Rusheng Song, Jun Lu, Xuwei Chen
An aqueous two-phase extraction system (ATPS) combined with an in situ dispersive liquid-liquid microextraction (DLLME) method using imidazolium ionic liquids (ILs) for the separation of curcuminoids is developed. The influence of structure of IL, the type of metathesis reagents, and the back extraction agents on the extraction efficiency is investigated. 2.0mg of curcuminoids are extracted by an IL ATPS composed of 0.4g 1,3-diethylimidazolium iodine (EeimI), 0.6g potassium hydrogen phosphate, 1.0g water. Then the bis[(trifluoromethyl)sulfonyl]imide lithium (LiNTf2) aqueous solution is added to the EeimI-rich phase of the ATPS. The water-immiscible ionic liquids, 1,3-diethylimidazole bis[(trifluoromethyl)sulfonyl]imide (EeimNTf2), forms by the metathesis reaction. The in situ DLLME is triggered simultaneously and further purifies the curcuminoids. 92% of EeimI transforms into EeimNTf2 and thus the Eeim⁺ cation is used for twice in this method. Finally, 0.1mol/L NaOH aqueous solution is used as the back extraction reagent. The curcuminoids precipitate is achieved with 93% of recovery when the aqueous solution is adjusted to pH 3.0. This ATPS-DLLME method is successfully applied to the separation of curcuminoids from Curcuma Longa (0.96±0.02% of extraction yield, a purity of >51% with respect to the total dry mass of the product).

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Layer-by-layer assembly of copper nanoparticles and manganese dioxide-multiwalled carbon nanotubes film: A new nonenzymatic electrochemical sensor for glucose

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Yan Wang, Sai Zhang, Wushuang Bai, Jianbin Zheng
A nonenzymatic glucose sensor based on Cu/MnO2/MWCNTs nanocomposite modified glass carbon electrode was fabricated by an electrochemical method. Transmission electron microscopic (TEM) measurement showed that MnO2 in the nanocomposite held a nanostructure of three-dimension (3D) spheres assembled by many densely arranged nanosheets. The electrocatalytic activity of the present sensor toward the oxidation of glucose was investigated by amperometry. The current response was linearly related to glucose concentration in a range from 6.4×10⁻⁷–2.0×10⁻³molL⁻¹ with a sensitivity of 494μAmM⁻¹cm⁻² and a correlation coefficient of 0.9990, and another range from 10 to 1000μM with a sensitivity of 1302μAmM⁻¹cm⁻² and a correlation coefficient of 0.9990. The detection limit was estimated to be 0.17μM at a signal-to-noise ratio of 3, and the response time was found to be 3s.

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Preparation of a novel ionic hybrid stationary phase by non-covalent functionalization of single-walled carbon nanotubes with amino-derivatized silica gel for fast HPLC separation of aromatic compounds

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Hayriye Aral, K. Serdar Çelik, Tarık Aral, Giray Topal
Single-walled carbon nanotubes (SWCNTs) were immobilized on spherical silica gel with a 4-μm average particle size and a 60-Å average pore size. The amino-derivatized silica gel was non-covalently coated with carboxylated SWCNTs to preserve the structure of the nanotubes and their physico–chemical properties. The novel ionic hybrid stationary phase was characterized by scanning electron microscopy (SEM), infra-red (IR) spectroscopy and elemental analysis, and then, it was used to fill an empty 150×4.6mm² high-performance liquid chromatography (HPLC) column. Chromatographic parameters, such as the theoretical plate number, retention factor and peak asymmetry factor, and analytical parameters, such as the limit of detection (LOD), limit of quantification (LOQ), linear range, calibration equation, and R² value, and quantitative analysis parameters were calculated for all of the analytes. Using different mobile phases, five different classes of aromatic hydrocarbons were separated in a very short analysis time of 4–8min. Furthermore, a high theoretical plate number (up to 25000) and an excellent peak asymmetry factor (1.0) were obtained. The results showed that the surface of the SWNTs had very strong interactions with aromatic groups, therefore providing high selectivity for the separation of different classes of aromatic compounds. This study indicates that SWCNTs enable the extension of the application range of the newly prepared stationary phases for the fast separation of aromatic compounds by HPLC.

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Detection of polychlorinated biphenyls in transformer oils in Vietnam by multiphoton ionization mass spectrometry using a far-ultraviolet femtosecond laser as an ionization source

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Vu Thi Thuy Duong, Vu Duong, Nghiem Thi Ha Lien, Tomoko Imasaka, Yuanyuan Tang, Shinpei Shibuta, Akifumi Hamachi, Do Quang Hoa, Totaro Imasaka
Polychlorinated biphenyls (PCBs) in transformer and food oils were measured using gas chromatography combined with multiphoton ionization mass spectroscopy. An ultrashort laser pulse emitting in the far-ultraviolet region was utilized for efficient ionization of the analytes. Numerous signal peaks were clearly observed for a standard sample mixture of PCBs when the third and fourth harmonic emissions (267 and 200nm) of a femtosecond Ti:sapphire laser (800nm) were employed. The signal intensities were found to be greater when measured at 200nm compared with those measured at 267nm, providing lower detection limits especially for highly chlorinated PCBs at shorter wavelengths. After simple pretreatment using disposable columns, PCB congeners were measured and found to be present in the transformer oils used in Vietnam.

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Recent developments in nanostructure based electrochemical glucose sensors

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Shabi Abbas Zaidi, Jae Ho Shin
Diabetes is a major health problem causing 4 million deaths each year and 171 million people suffering worldwide. Although there is no cure for diabetes, nevertheless, the blood glucose level of diabetic patients should be monitored tightly to avoid further complications. Thus, monitoring of glucose in blood has become an inevitable need leading to fabrication of accurate and sensitive advanced blood sugar detection devices for clinical diagnosis and personal care. It led to the development of enzymatic glucose sensing approach. Later on, various types of nanostructures have been utilized owing to their high surface area, great stability, and cost effectiveness for the fabrication of enzymatic as well as for nonenzymatic glucose sensing approach. This work reviews on both categories, however it is not intended to discuss all the research reports published regarding nanostructure based enzymatic and nonenzymatic approaches between mid-2010 and mid-2015. We, do, however, focused to describe the details of many substantial articles explaining the design of sensors, and utilities of the prepared sensors, so that readers might get the principles behind such devices and relevant detection strategies. This work also focuses on biocompatibility and toxicity of nanomaterials as well as provides a critical opinion and discussions about misconceptions in glucose sensors.

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Target analysis and retrospective screening of veterinary drugs, ergot alkaloids, plant toxins and other undesirable substances in feed using liquid chromatography–high resolution mass spectrometry

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Nuria León, Agustín Pastor, Vicent Yusà
A comprehensive strategy combining a quantitative method for 77 banned veterinary drugs, mycotoxins, ergot alkaloids and plant toxins, and a post-target screening for 425 substances including pesticides and environmental contaminants in feed were developed using a QuEChERS-based extraction and an ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC–HRMS).The quantitative method was validated after previous statistical optimisation of the main parameters governing ionisation, and presented recoveries ranging, in general, from 80 to 120%, with a precision in terms of Relative Standard Deviation (RSD) lower than 20%. The full-scan accurate mass data were acquired with a resolving power of 50000 FWHM and a mass accuracy lower than 5ppm. The method LOQ was lower than 12.5µgkg⁻¹ for the majority of the veterinary drugs and plant toxins and 20µgkg⁻¹ for ergot alkaloids.For post-target screening a customised theoretical database including the exact mass, the polarity of acquisition and the expected adducts was built and used for post-run retrospective screening. The analytical strategy was applied to 32 feed samples collected from farms of the Valencia Region (Spain). Florfenicol, zearalenone and atropine were identified and quantified at concentrations around 10µgkg⁻¹. In the post-target screening of the real samples, Sulfadiazine, Thrimetoprin and Pirimiphosmethyl were tentatively identified.

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Development and validation of a laser-induced breakdown spectroscopic method for ultra-trace determination of Cu, Mn, Cd and Pb metals in aqueous droplets after drying

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Nadir Aras, Şerife Yalçın
The present study reports a fast and accurate methodology for laser-induced breakdown spectroscopic, LIBS, analysis of aqueous samples for environmental monitoring purposes. This methodology has two important attributes: one is the use of a 300nm oxide coated silicon wafer substrate (Si+SiO2) for the first time for manual injection of 0.5 microliter aqueous metal solutions, and two is the use of high energy laser pulses focused outside the minimum focus position of a plano convex lens at which relatively large laser beam spot covers the entire droplet area for plasma formation. Optimization of instrumental LIBS parameters like detector delay time, gate width and laser energy has been performed to maximize atomic emission signal of target analytes; Cu, Mn, Cd and Pb. Under the optimal conditions, calibration curves were constructed and enhancements in the LIBS emission signal were obtained compared to the results of similar studies given in the literature. The analytical capability of the LIBS technique in liquid analysis has been improved. Absolute detection limits of 1.3pg Cu, 3.3pg Mn, 79pg Cd and 48pg Pb in 0.5 microliter volume of droplets were obtained from single shot analysis of five sequential droplets. The applicability of the proposed methodology to real water samples was tested on the Certified Reference Material, Trace Metals in Drinking Water, CRM-TMDW and on ICP multi-element standard samples. The accuracy of the method was found at a level of minimum 92% with relative standard deviations of at most 20%. Results suggest that 300nm oxide coated silicon wafer has an excellent potential to be used as a substrate for direct analysis of contaminants in water supplies by LIBS and further research, development and engineering will increase the performance and applicability of the methodology.

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Immersion liquid techniques in solid particle characterization: A review

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Ilpo Niskanen, Kenichi Hibino, Jukka Räty
Chemical, physical and optical properties of small solid particles are widely utilized in our everyday merchandises. For example, tailored particles embedded in paper or cosmetics improve the visual appearance of the products substantially. As a consequence of the small size of particles, one particle characterization tool is a microscope. It may provide e.g. the particle size, shape and the refractive index. The determination of the refractive index, using the microscope, typically exploited the so-called immersion liquid method. In this review, we provide an overview of non-imaging immersion matching techniques including immersion liquid set, the temperature, the wavelength, the double variation and the liquid evaporation methods. The basic features, benefits and limitations of each technique have been described followed by examples of potential applications in a quality monitoring of particle suspensions and colloids in industry.

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Fabrication of an ionic liquid-based macroporous polymer monolithic column via atom transfer radical polymerization for the separation of small molecules

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Hang Zhang, Ligai Bai, Zhen Wei, Sha Liu, Haiyan Liu, Hongyuan Yan
A polymer monolithic column was prepared in a stainless steel column (50×4.6mm i.d.) via atom transfer radical polymerization technique using triallyl isocyanurate and ionic liquid (1-allyl-3-methylimidazolium chloride) as co-monomers, ethylene dimethacrylate as cross linking agent, polyethylene glycol 200, 1,4-butanediol, and N, N- dimethylformamide as porogen system, CCl4 as initiator, and FeCl2 as catalyst. The optimized polymer columns were characterized by scanning electron microscope, nitrogen adsorption-desorption instrument, mercury intrusion porosimetry, infrared spectrometer, and thermogravimetric analysis technique. Respectively, all of these factors above could illustrate that the optimized columns had relative uniform macroporous structure and high thermal stability. A series of basic and acidic small molecules, isomers, and homologues were used to evaluate the performance of these monoliths and enhanced column efficiency was obtained.

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Study of consumer fireworks post-blast residues by ATR-FTIR

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Carlos Martín-Alberca, Félix Zapata, Héctor Carrascosa, Fernando E. Ortega-Ojeda, Carmen García-Ruiz
Specific analytical procedures are requested for the forensic analysis of pre- and post-blast consumer firework samples, which present significant challenges. Up to date, vibrational spectroscopic techniques such as Fourier transform infrared spectroscopy (FTIR) have not been tested for the analysis of post-blast residues in spite of their interesting strengths for the forensic field. Therefore, this work proposes a simple and fast procedure for the sampling and analysis of consumer firework post-blast residues by a portable FTIR instrument with an Attenuated Total Reflection (ATR) accessory. In addition, the post-blast residues spectra of several consumer fireworks were studied in order to achieve the identification of their original chemical compositions. Hence, this work analysed 22 standard reagents usually employed to make consumer fireworks, or because they are related to their combustion products. Then, 5 different consumer fireworks were exploded, and their residues were sampled with dry cotton swabs and directly analysed by ATR-FTIR. In addition, their pre-blast fuses and charges were also analysed in order to stablish a proper comparison. As a result, the identification of the original chemical compositions of the post-blast samples was obtained. Some of the compounds found were potassium chlorate, barium nitrate, potassium nitrate, potassium perchlorate or charcoal. An additional study involving chemometric tools found that the results might greatly depend on the swab head type used for the sampling, and its sampling efficiency. The proposed procedure could be used as a complementary technique for the analysis of consumer fireworks post-blast residues.

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Ultrasonic frequency analysis for estimating pH in albumin-rich biofluids

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Andrien A. Rackov, David H. Burns
Ultrasound is known as a non-invasive imaging modality capable of propagating through highly scattering media such as tissue, blood, and other biological fluids, yet currently provides little chemical information. We have developed a straightforward and rapid methodology for estimating pH in albumin-rich biofluids based on analysis of ultrasonic frequencies. Albumin is the most abundant protein in serum and undergoes conformational changes with pH. It was shown that when ultrasound propagated through albumin solutions, the attenuation of collected ultrasound signals increased with pH. By measuring the ultrasound frequency spectra at several albumin concentrations and pH values, the pH of the solutions could be determined by multilinear regression. Differences in absolute protein content contributed to signal differences in the frequency profiles and were minimized through normalization of each spectrum by the sum of all its frequency intensities. This strategy was applied to human serum samples from multiple donors, for which a multilinear regression model was developed with a coefficient of determination (R²) of 0.93 and a standard error of estimate (SEE) of 0.08 pH units. The use of albumin as a pH indicator opens the doors for estimations in other albumin-rich media, such as amniotic fluid and cerebrospinal fluid.



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Ultrasound-assisted extraction of azadirachtin from dried entire fruits of Azadirachta indica A. Juss. (Meliaceae) and its determination by a validated HPLC-PDA method

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Joelma Abadia Marciano de Paula, Lucas Ferreira Brito, Karen Lorena Ferreira Neves Caetano, Mariana Cristina de Morais Rodrigues, Leonardo Luiz Borges, Edemilson Cardoso da Conceição
Azadirachta indica A. Juss., also known as neem, is a Meliaceae family tree from India. It is globally known for the insecticidal properties of its limonoid tetranortriterpenoid derivatives, such as azadirachtin. This work aimed to optimize the azadirachtin ultrasound-assisted extraction (UAE) and validate the HPLC-PDA analytical method for the measurement of this marker in neem dried fruit extracts. Box–Behnken design and response surface methodology (RSM) were used to investigate the effect of process variables on the UAE. Three independent variables, including ethanol concentration (%, w/w), temperature (°C), and material-to-solvent ratio (gmL⁻¹), were studied. The azadirachtin content (µgmL⁻¹), i.e., dependent variable, was quantified by the HPLC-PDA analytical method. Isocratic reversed-phase chromatography was performed using acetonitrile/water (40:60), a flow of 1.0mLmin⁻¹, detection at 214nm, and C18 column (250×4.6mm², 5µm). The primary validation parameters were determined according to ICH guidelines and Brazilian legislation. The results demonstrated that the optimal UAE condition was obtained with ethanol concentration range of 75–80% (w/w), temperature of 30°C, and material-to-solvent ratio of 0.55gmL⁻¹. The HPLC-PDA analytical method proved to be simple, selective, linear, precise, accurate and robust. The experimental values of azadirachtin content under optimal UAE conditions were in good agreement with the RSM predicted values and were superior to the azadirachtin content of percolated extract. Such findings suggest that UAE is a more efficient extractive process in addition to being simple, fast, and inexpensive.

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Utilization of deep eutectic solvents as novel mobile phase additives for improving the separation of bioactive quaternary alkaloids

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Ting Tan, Mingliang Zhang, Yiqun Wan, Hongdeng Qiu
Deep eutectic solvents (DESs) were used as novel mobile phase additives to improve chromatographic separation of four quaternary alkaloids including coptisine chloride, sanguinarine, berberine chloride and chelerythrine on a C18 column. DESs as a new class of ionic liquids are renewably sourced, environmentally benign, low cost and easy to prepare. Seven DESs were obtained by mixing different hydrogen acceptors and hydrogen-bond donors. The effects of organic solvents, the concentration of DESs, the types of DESs and the pH values of the buffer solution on the separation of the analytes were investigated. The composition of acetonitrile and 1.0% deep eutectic solvents aqueous solution (pH 3.3, adjusted with hydrochloric acid) in a 32:68 (v/v) ratio was used as optimized mobile phase, with which four quaternary alkaloids were well separated. When a small amount of DESs was added in the mobile phase for the separation of alkaloids on the C18 column, noticeable improvements were distinctly observed such as decreasing peak tailing and improving resolution. The separation mechanism mediated by DESs as mobile phase additives can be attributed to combined effect of both hydrogen acceptors and hydrogen-bond donors. For example, choline chloride can effectively cover the residual silanols on silica surface and ethylene glycol can reduce the retention time of analytes. The proposed method has been applied to determine BerbC in Lanqin Chinese herbal oral solution and BerbC tablet. Utilization of DESs in mobile phase can efficiently improve separation and selectivity of analytes from complex samples.

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Development of Hf4+-immobilized polydopamine-coated magnetic graphene for highly selective enrichment of phosphopeptides

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Haizhu Lin, Chunhui Deng
In this work, we first designed and synthesized an IMAC material with Hf⁴⁺ immobilized on polydopamine-coated magnetic graphene and applied it to phosphopeptides enrichment successfully. The newly prepared material gathered the advantages of large specific surface area of graphene, good hydrophilicity and biocompatibility of polydopamine and superparamagnetism of Fe3O4. We investigated the performance of Hf⁴⁺-immobilized polydopamine-coated magnetic graphene (denoted as magG@PDA-Hf⁴⁺) in phosphopeptides enrichment and the results showed high selectivity and sensitivity of the new material. Finally, we successfully applied magG@PDA-Hf⁴⁺ to phosphopeptides enrichment from non-fat milk digests and human serum, further demonstrating excellent performance of this new material in phosphopeptides enrichment.

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Cationic-perylene-G-quadruplex complex based fluorescent biosensor for label-free detection of Pb2+

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Xu-Hua Zhao, Liang Gong, Yuan Wu, Xiao-Bing Zhang, Jun Xie
In this work we use a water-soluble cationic perylene derivative (compound 1) as the G-quadruplex (G4) structure fluorescence indicator to construct a fluorescent biosensor for simple, rapid and label-free detection of Pb²⁺. In the absence of Pb²⁺, strong electrostatic interactions between compound 1 and the G-rich DNA probe (PW17) induced the aggregation of compound 1 and resulted in the fluorescence quenching. In the presence of Pb²⁺, the PW17 formed Pb²⁺-stabilized G4 structure, which reduced the aggregation of compound 1 and gave rise to high fluorescence. This allowed us to use convenient "mix-and-detect" protocol for quantitative analysis of Pb²⁺. Since Pb²⁺ can specially induce PW17 to form compact DNA fold, our proposed biosensor displayed high selectivity for Pb²⁺. It also exhibited a high sensitivity to Pb²⁺, with a limit of detection of 5.0nM observed. Furthermore, the biosensor was applied for the detection of Pb²⁺ in urine and paint samples, and both showed satisfactory results.

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Development and evaluation of an ELIME assay to reveal the presence of Salmonella in irrigation water: Comparison with Real-Time PCR and the Standard Culture Method

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): G. Volpe, E. Delibato, L. Fabiani, E. Pucci, S. Piermarini, A. D'Angelo, F. Capuano, D. De Medici, G. Palleschi
A reliable, low-cost and easy-to-use ELIME (Enzyme-Linked-Immuno-Magnetic-Electrochemical) assay for detection of Salmonella enterica in irrigation water is presented. Magnetic beads (MBs), coupled to a strip of eight-magnetized screen-printed electrodes localized at the bottom of eight wells (8-well/SPE strip), effectively supported a sandwich immunological chain. Enzymatic by-product is quickly measured by chronoamperometry, using a portable instrument. With the goal of developing a method able to detect a wide range of Salmonella serotypes, including S. Napoli and S. Thompson strains responsible for various community alerts, different kinds of MBs, antibodies and blocking agents were tested. The final system employs MBs coated with a broad reactivity monoclonal antibody anti-salmonella and blocked with dry milk. For a simple and rapid assay these two steps were performed in a preliminary phase, while the two sequential incubations for the immuno-recognition events were merged in a single step of 1h. In parallel a Real-Time PCR (RTi-PCR) method, based on a specific locked nucleic acid (LNA) fluorescent probe and an internal amplification control (IAC), was carried out. The selectivity of the ELIME and RTi-PCR assays was proved by inclusivity and exclusivity tests performed analyzing different Salmonella serotypes and non-target microorganisms, most commonly isolated from environmental sources. Furthermore, both methods were applied to experimentally and not experimentally contaminated irrigation water samples. Results confirmed by the ISO culture method, demonstrated the effectiveness of ELIME and RTi-PCR assays to detect a low number of salmonella cells (1-10 CFU/L) reducing drastically the long analysis time usually required to reveal this pathogen.

Graphical abstract

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Quantitative analysis of dicamba residues in raw agricultural commodities with the use of ion-pairing reagents in LC–ESI–MS/MS

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): Hongyue Guo, Leah S Riter, Chad E Wujcik, Daniel W Armstrong
A sensitive and selective HPLC–MS/MS method was developed for the quantitative analysis of dicamba residues in raw agricultural commodities (RACs). Instead of analysis in the traditionally used negative electrospray ionization (ESI) mode, these anionic compounds were detected in positive ESI with the use of ion-pairing reagents. In this approach, only a small amount (60µM) of a commercially available dicationic ion-pairing reagent was introduced into the post-column sample stream. This method has been validated in six different types of RACs including corn grain, corn stover, cotton seed, soybean, soy forage and orange with satisfactory quantitative accuracy and precision. The limits of quantitation (LOQ) values for these analytes were 1.0 to 3.0µg/kg. The standard curves were linear over the range of the tested concentrations (3.0 to 500µg/kg), with correlation coefficient (r) values≥0.999. Evaluation of ionization effects in RAC matrix extracts using diluent blanks for comparison showed no significant matrix effects were present.

Graphical abstract

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Sensitive immunochemical approaches for quantitative (FPIA) and qualitative (lateral flow tests) determination of gentamicin in milk

Publication date: 1 March 2016
Source:Talanta, Volume 149
Author(s): N.V. Beloglazova, P.S. Shmelin, S.A. Eremin
Three kinds of immunoassays for the determination of gentamicin in milk samples were developed and validated. First, a fast and easily-performed fluorescence polarization immunoassay was used for characterization of the employed polyclonal antibody. The calculated Kaff were (1.9±0.4)×10⁹М⁻¹ and (6.0±0.2)×10⁶М⁻¹ for the high- and low-affinity fractions respectively. The assay was characterized with a good sensitivity, the limit of detection being 5μgkg⁻¹. Two different kinds of detection labels, i.e. colloidal gold (CG) and quantum dots (QDs), were evaluated for use in lateral-flow format with respect to rapid visual on-site testing. The cut-off levels for both qualitative formats were selected based on the maximum level for gentamicin in milk established by the European Commission, 100μgkg⁻¹, resulting in a 10μgkg⁻¹ cut-off considering sample dilution. The intra-laboratory validation was performed with sterilized milk samples artificially spiked with gentamicin at concentrations less than, equal to, and greater than the cut-off level. It was shown that milk products could be analyzed without any sample preparation, except for dilution with the buffer solution. The rates of false-positive and false-negative results were below 5% for both labels. The different developed immunoassays were tested towards gentamicin determination in artificially-spiked and naturally contaminated milk samples.

Graphical abstract

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Effluent Tenascin-C Levels Reflect Peritoneal Deterioration in Peritoneal Dialysis: MAJOR IN PD Study

Peritoneal deterioration causing structural changes and functional decline is a major complication of peritoneal dialysis (PD). The aim of this study was to explore effluent biomarkers reflecting peritoneal deterioration. In an animal study, rats were intraperitoneally administered with PD fluids adding 20 mM methylglyoxal (MGO) or 20 mM formaldehyde (FA) every day for 21 days. In the MGO-treated rats, tenascin-C (TN-C) levels in the peritoneal effluents were remarkably high and a cluster of TN-C-positive mesothelial cells with epithelial-to-mesenchymal transition- (EMT-) like change excessively proliferated at the peritoneal surface, but not in the FA-treated rats. Effluent matrix metalloproteinase-2 (MMP-2) levels increased in both the MGO- and FA-treated rats. In a clinical study at 18 centers between 2006 and 2013, effluent TN-C and MMP-2 levels were quantified in 182 PD patients with end-stage renal disease. Peritoneal function was estimated using the peritoneal equilibration test (PET). From the PET results, the D/P Cr ratio was correlated with effluent levels of TN-C (ρ = 0.57, ) and MMP-2 (ρ = 0.73, ). We suggest that TN-C in the effluents may be a diagnostic marker for peritoneal deterioration with EMT-like change in mesothelial cells in PD.

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Experimental Analysis of the Mechanism of Hearing under Water

The mechanism of human hearing under water is debated. Some suggest it is by air conduction (AC), others by bone conduction (BC), and others by a combination of AC and BC. A clinical bone vibrator applied to soft tissue sites on the head, neck, and thorax also elicits hearing by a mechanism called soft tissue conduction (STC) or nonosseous BC. The present study was designed to test whether underwater hearing at low intensities is by AC or by osseous BC based on bone vibrations or by nonosseous BC (STC). Thresholds of normal hearing participants to bone vibrator stimulation with their forehead in air were recorded and again when forehead and bone vibrator were under water. A vibrometer detected vibrations of a dry human skull in all similar conditions (in air and under water) but not when water was the intermediary between the sound source and the skull forehead. Therefore, the intensities required to induce vibrations of the dry skull in water were significantly higher than the underwater hearing thresholds of the participants, under conditions when hearing by AC and osseous BC is not likely. The results support the hypothesis that hearing under water at low sound intensities may be attributed to nonosseous BC (STC).

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Proceedings Fifth ESWI Influenza Conference

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49
Author(s): A.D.M.E. Osterhaus, Chris Vanlangendonck




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Editorial Board/Aims and Scope

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49





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Influenza vaccines: Where do we stand? Where do we go?

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49
Author(s): Guus Rimmelzwaan, Isabel Leroux-Roels, Sarah Gilbert, Angus Thomson




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Conclusions: From peer to peer communication to communicating with policy makers and the general public

Publication date: 8 December 2015
Source:Vaccine, Volume 33, Issue 49





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The confounded effects of age and exposure history in response to influenza vaccination

Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Ana Mosterín Höpping, Janet McElhaney, Judith M. Fonville, Douglas C. Powers, Walter E.P. Beyer, Derek J. Smith
Numerous studies have explored whether the antibody response to influenza vaccination in elderly adults is as strong as it is in young adults. Results vary, but tend to indicate lower post-vaccination titers (antibody levels) in the elderly, supporting the concept of immunosenescence—the weakening of the immunological response related to age. Because the elderly in such studies typically have been vaccinated against influenza before enrollment, a confounding of effects occurs between age, and previous exposures, as a potential extrinsic reason for immunosenescence.We conducted a four-year study of serial annual immunizations with inactivated trivalent influenza vaccines in 136 young adults (16 to 39 years) and 122 elderly adults (62 to 92 years). Compared to data sets of previously published studies, which were designed to investigate the effect of age, this detailed longitudinal study with multiple vaccinations allowed us to also study the effect of prior vaccination history on the response to a vaccine.In response to the first vaccination, young adults produced higher post-vaccination titers, accounting for pre-vaccination titers, than elderly adults. However, upon subsequent vaccinations the difference in response to vaccination between the young and elderly age groups declined rapidly. Although age is an important factor when modeling the outcome of the first vaccination, this term lost its relevance with successive vaccinations. In fact, when we examined the data with the assumption that the elderly group had received (on average) as few as two vaccinations prior to our study, the difference due to age disappeared.Our analyses therefore show that the initial difference between the two age groups in their response to vaccination may not be uniquely explained by immunosenescence due to ageing of the immune system, but could equally be the result of the different pre-study vaccination and infection histories in the elderly.



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Nasopharyngeal carriage of Streptococcus pneumoniae and other bacteria in the 7th year after implementation of the pneumococcal conjugate vaccine in the Netherlands

Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Astrid A.T.M. Bosch, Marlies A. van Houten, Jacob P. Bruin, Alienke J. Wijmenga-Monsuur, Krzysztof Trzciński, Debby Bogaert, Nynke Y. Rots, Elisabeth A.M. Sanders
After introduction of 7-valent pneumococcal conjugate vaccine (PCV7) in the infant national immunization program (NIP) in the Netherlands in 2006, Streptococcus pneumoniae strains of the non-vaccine serotype 19A became the dominant in carriage in children and their parents. Similar patterns were observed in other European countries and the United States. Increases in carriage rates of Staphylococcus aureus and non-typeable (NT) Haemophilus influenzae were also observed. After switching of PCV7 to 10-valent vaccine (PCV10) in 2011, a new carriage surveillance study was performed in the winter of 2012/2013. Nasopharyngeal carriage of S. pneumoniae, H. influenzae, S. aureus, and Moraxella catarrhalis was determined by conventional culture in 330 PCV10-vaccinated 11-month-old children, 330 PCV7-vaccinated 24-month-old children, and their parents. Carriage prevalence was compared with similar carriage studies conducted in 2005, 2009, and 2010/2011. Although serotype 19A remained the most frequently carried pneumococcal serotype in children, prevalence of 19A significantly declined in PCV7-vaccinated 24-month-old children (14% to 8%, p=0.01), but less in PCV10-vaccinated 11-month-old children (12% to 9%, p=0.31). Carriage of H. influenzae remained stable at an elevated level (65% in 11-month-olds and 69% in 24-month-olds), while the carriage of S. aureus returned to pre-PCV7 levels in 11-month-old children (14% in 2010/2011 to 7% in 2012/2013), but not in 24-month-olds (remained at 7%). Our results might indicate a new balance between replacing non-vaccine pneumococcal serotypes and other potential pathogenic bacteria in nasopharyngeal carriage. Carriage studies are valuable tools in assessing vaccine effects on pathogens circulating in the population, for evaluation of PCV impact, and in predicting changes in respiratory and invasive disease.



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National hospital data for intussusception: Data linkage and retrospective analysis to assess quality and use in vaccine safety surveillance

Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Lamiya Samad, Mario Cortina-Borja, Alastair G. Sutcliffe, Sean Marven, J. Claire Cameron, Haitham El Bashir, Richard Lynn, Brent Taylor
ObjectivesTo assess the quality of national Hospital Episode Statistics (HES) data for intussusception, and evaluate this routinely collected database for rotavirus vaccine safety surveillance by estimating pre-vaccination trends in intussusception hospitalisation.MethodsData linkage was performed between HES and prospective intussusception data from the British Paediatric Surveillance Unit (BPSU), followed by capture–recapture analysis to verify HES data quality. Inclusion criteria were infants aged less than 12 months and admitted for intussusception to National Health Service (NHS) hospitals in England from March 2008 to March 2009. To estimate pre-vaccination incidence rates of intussusception, we performed a retrospective analysis of HES data. Infants aged less than 12 months and admitted for intussusception to NHS hospitals in England between 1995 and 2009 were included.ResultsData linkage between 254 cases of intussusception identified in HES data and 190 cases reported via the BPSU resulted in 163 cases common to both data sources. Of remaining 91 cases in HES, 37 had confirmed intussusception. HES data accuracy was 78.7% (200 confirmed/254 cases) and completeness for intussusception was 86% (163 matched/190 BPSU cases) compared to 81.5% (163 matched/200 HES cases) for BPSU. A total of 233 (95% CI: 227.4 to 238.8) intussusception cases were estimated for the infant population (2008 to 2009). For retrospective analysis, of 6462 intussusception admissions in HES data (1995 to 2009), 1594 (24.7%) were duplicate admissions. A declining trend in intussusception incidence was observed in the infant population, from 86/100,000 in 1997 to 34/100,000 in 2009 (60% reduction, P<0.001). Cosinor modelling showed an excess of cases among infants in winter and spring (P<0.001, n=4957, 1995 to 2009).ConclusionNational hospital data capture the majority of admissions for intussusception and should be considered for the post-implementation surveillance of rotavirus vaccine safety in England.



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Optimization of physiological properties of hydroxyapatite as a vaccine adjuvant

Publication date: Available online 5 December 2015
Source:Vaccine
Author(s): Masayuki Hayashi, Taiki Aoshi, Yasumichi Kogai, Daisuke Nomi, Yasunari Haseda, Etsushi Kuroda, Kouji Kobiyama, Ken J. Ishii
Various particles such as Alum or silica are known to act as an adjuvant if co-administered with vaccine antigens. Several reports have demonstrated that the adjuvanticity is strongly affected by the physicochemical properties of particles such as the size, shape and surface charge, although the required properties and its relationship to the adjuvanticity are still controversial. Hydroxyapatite particle (HAp) composed of calcium phosphate has been shown to work as adjuvant in mice. However, the properties of HAp required for the adjuvanticity have not been fully characterized yet. In this study, we examined the role of size or shape of HAps in the antibody responses after immunization with antigen. HAps whose diameter ranging between 100 and 400nm provided significantly higher antibody responses than smaller or larger ones. By comparison between sphere and rod shaped HAps, rod shaped HAps induced stronger inflammasome-dependent IL-1β production than the sphere shaped ones in vitro. However, sphere- and rod-shaped HAp elicited comparable antibody response in WT mice. Vice versa, Nlrp3^−/−, Asc^−/− or Caspase1^−/− mice provided comparable level of antibody responses to HAp adjuvanted vaccination. Collectively, our results demonstrated that the size rather than shape is a more critical property, and IL-1β production via NLRP3 inflammasome is dispensable for the adjuvanticity of HAps in mice.



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Evaluation of the In Vivo and In Vitro Effects of Fructose on Respiratory Chain Complexes in Tissues of Young Rats

Hereditary fructose intolerance (HFI) is an autosomal-recessive disorder characterized by fructose and fructose-1-phosphate accumulation in tissues and biological fluids of patients. This disease results from a deficiency of aldolase B, which metabolizes fructose in the liver, kidney, and small intestine. We here investigated the effect of acute fructose administration on the activities of mitochondrial respiratory chain complexes, succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) in cerebral cortex, liver, kidney, and skeletal muscle of male 30-day-old Wistar rats. The rats received subcutaneous injection of sodium chloride (0.9%; control group) or fructose solution (5 μmol/g; treated group). One hour later, the animals were euthanized and the cerebral cortex, liver, kidney, and skeletal muscle were isolated and homogenized for the investigations. Acute fructose administration increased complex I-III activity in liver. On the other hand, decreased complexes II and II-III activities in skeletal muscle and MDH in kidney were found. Interestingly, none of these parameters were affected in vitro. Our present data indicate that fructose administration elicits impairment of mitochondrial energy metabolism, which may contribute to the pathogenesis of the HFI patients.

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EEG Derived Neuronal Dynamics during Meditation: Progress and Challenges

Meditation advances positivity but how these behavioral and psychological changes are brought can be explained by understanding neurophysiological effects of meditation. In this paper, a broad spectrum of neural mechanics under a variety of meditation styles has been reviewed. The overall aim of this study is to review existing scientific studies and future challenges on meditation effects based on changing EEG brainwave patterns. Albeit the existing researches evidenced the hold for efficacy of meditation in relieving anxiety and depression and producing psychological well-being, more rigorous studies are required with better design, considering client variables like personality characteristics to avoid negative effects, randomized controlled trials, and large sample sizes. A bigger number of clinical trials that concentrate on the use of meditation are required. Also, the controversial subject of epileptiform EEG changes and other adverse effects during meditation has been raised.

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