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Globally, around six billion people consume bovine milk. As in many other countries dairy plays an important role in the Indian diet. The Food Safety Standards Authority of India is continuously taking efforts to ensure the country's regulatory framework for the dairy sector meets international standards and secure human health and to promote trade. To ensure safe and nutritious milk and milk products, an integrated quality assurance system with a thorough surveillance program is a prerequisite. This paper outlines the risk assessment principles before listing various chemical and microbiological hazards in the dairy supply chain, discusses examples with successful dairy supply chains, suggests analytical approaches for regulatory control, and gives recommendations for an effective surveillance plan. First of its kind, the paper may contribute to the development of an integrated milk quality and safety surveillance system in India, and may also serve as guidance for other developing nations. • FSSAI strives to ensure quality and food safety in the dairy sector. • India aims to upgrade its regulatory framework to meet international standards. • Examples of structured surveillance systems in several dairy supply chains are shown. • Recommendations for building a well-planned surveillance system in India are given. [ABSTRACT FROM AUTHOR]

Pediatric high-grade gliomas (pHGGs) are the leading cause of cancer-related deaths in children in the USA. Sixteen percent of hemispheric pediatric and young adult HGGs encode Gly34Arg/Val substitutions in the histone H3.3 (H3.3-G34R/V). The mechanisms by which H3.3-G34R/V drive malignancy and therapeutic resistance in pHGGs remain unknown. Using a syngeneic, genetically engineered mouse model (GEMM) and human pHGG cells encoding H3.3-G34R, we demonstrate that this mutation led to the downregulation of DNA repair pathways. This resulted in enhanced susceptibility to DNA damage and inhibition of the DNA damage response (DDR). We demonstrate that genetic instability resulting from improper DNA repair in G34R-mutant pHGG led to the accumulation of extrachromosomal DNA, which activated the cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway, inducing the release of immune-stimulatory cytokines. We treated H3.3-G34R pHGG-bearing mice with a combination of radiotherapy (RT) and DNA damage response inhibitors (DDRi) (i.e., the blood-brain barrier-permeable PARP inhibitor pamiparib and the cell-cycle checkpoint CHK1/2 inhibitor AZD7762), and these combinations resulted in long-term survival for approximately 50% of the mice. Moreover, the addition of a STING agonist (diABZl) enhanced the therapeutic efficacy of these treatments. Long-term survivors developed immunological memory, preventing pHGG growth upon rechallenge. These results demonstrate that DDRi and STING agonists in combination with RT induced immune-mediated therapeutic efficacy in G34-mutant pHGG. [ABSTRACT FROM AUTHOR]

Background: Residues of polar pesticides cannot be determined by QuEChERS-based multiresidue extractions because of their non-amenability to reverse-phase chromatographic separation and poor recoveries. On the other hand, single-residue methods pose limitations because of the various requirements of sample preparation and LC-MS/MS conditions. A new multiresidue method is thus warranted for rapid and simultaneous analysis of polar pesticides. Objective: The study developed a multiresidue method for the simultaneous analysis of glyphosate and its metabolite (aminomethylphosphonic acid, AMPA), glufosinate and its metabolites (3-methylphosphinicopropionic acid and N-acetylglufosinate), ethephon, fosetyl-aluminum and its metabolite (phosphonic acid), and trimesiumin grape and pomegranate by LC-MS/MS. Method: The homogenized samples (10 g) were extracted with acidified methanol (20 mL). An aliquot of the extract was diluted with acetonitrile (1+1) and measured by LC-MS/MS using a Torus DEA column. The performance of a hydrophilic interaction liquid chromatography (HILIC) column and an "anionic polar pesticides" (APP) column was also evaluated. Results: The method performance on the Torus DEA column was satisfactory for all compounds (recoveries = 77-104%, repeatability-RSD, <11%) at limit of quantification (LOQ) (0.01 mg/kg), and with higher levels in grape and pomegranate. The only exception was AMPA, which had an LOQ of 0.05 mg/kg. In the APP column, AMPA could be determined with an LOQ of 0.01 mg/kg. Trimesium, which had poor retention in Torus DEA, performed better in an XBridge HILIC column (retention time = 4.2 min, LOQ = 0.01 mg/kg). The inter-laboratory validation experiment yielded comparable results with high accuracy and precision. Conclusions: The method could screen the residues of all compounds on a Torus DEA column. For AMPA and trimesium, the APP and XBridge HILIC columns provided superior method performances. Since isotopically labeled internal standards were not required, the method appeared cost-effective. Considering its compliance with the SANTE/12682/2019 validation guidelines and EU-MRLs, the method can be recommended for regulatory testing purposes. Highlights: A high-throughput residue analysis method targeting nine polar and ionic compounds in grape and pomegranate involved a single multiresidue extraction, followed by direct analysis using LC-MS/MS. A satisfactory method performance was achieved through intra- and inter-laboratory validation. The method sensitivity met the EU-MRLs and the SANTE/ 12682/2019 analytical quality control criteria. [ABSTRACT FROM AUTHOR]

The SCALE code system developed at Oak Ridge National Laboratory includes state-of-the-art capabilities for radiation source term and radiation transport simulations that can be used in numerous applications, including dose rate analyses of complex consolidated interim storage facilities (CISFs). A licensed CISF could be used to store tens of thousands of tonnes of spent nuclear fuel discharged from commercial power reactors using various cask and storage pad designs. A CISF design must comply with the regulatory requirements provided in 10 CFR Part 72, including requirements related to annual dose limits applicable to real individuals located beyond the area controlled by the licensee. Therefore, calculating a dose to the public is a necessary part of the licensing process for the construction of a CISF. These calculations are very challenging because of the complexity of the CISF design and the low magnitude of dose rate at large distances from the facility. This paper describes detailed far-field dose rate calculations performed for a proposed CISF using MAVRIC, the Monte Carlo radiation shielding sequence in SCALE 6.2.3, with automated variance reduction based on discrete ordinates calculations. The method presented in this paper uses a detailed Monte Carlo radiation transport simulation in one step from source to dose rate. A series of independent simulations was made using the complete site geometry (all casks present), but with only one cask containing radiation sources to obtain the dose rate maps produced by each storage cask. The CISF dose rate map was obtained by adding the dose rate maps produced by the independent individual cask simulations. Ample volumes of air and soil extending beyond the location of interest for dose rate calculation were included in the calculation model to properly simulate important radiation attenuation and scattering events that affect far-field dose rates. A comprehensive sensitivity study is included in this paper to illustrate the importance of selecting appropriate air volume, mass density, and composition for CISF skyshine dose rate calculations. Dry soil and soil containing water were analyzed to determine their effects on groundshine radiation. [ABSTRACT FROM AUTHOR]

Undesired toxicity and emergence of multidrug resistance (MDR) are the major impediments to the successful application of organotin-based compounds against cancer. Since oxalyl-bis(N-phenyl)hydroxamic acid (OBPHA) exerts significant efficacy against cancer, we believe that derivatives of OBPHA including organotin molecule can show a promising effect against cancer. Herein, we have selected three previously characterized OBPHA derivatives viz., succinyl-bis(N-phenyl)hydroxamic acid (SBPHA), diphenyl-tin succinyl-bis(N-phenyl)hydroxamic acid (Sn-SBPHA), malonyl-bis(N-phenyl)hydroxamic acid (MBPHA) and evaluated their antiproliferative efficacy against both drug-resistant (CEM/ADR5000; EAC/Dox) and sensitive (CCRF-CEM; HeLa; EAC/S) cancers. Data revealed that Sn-SBPHA selectively targets drug-resistant and sensitive cancers without inducing any significant toxicity to normal cells (Chang Liver). Moreover, shortening of the backbone of SBPHA enhances the efficacy of the newly formed molecule MBPHA by targeting only drug-sensitive cancers. Sn-SBPHA induces caspase3-dependent apoptosis through redox-imbalance in both drug-resistant and sensitive cancer. Sn-SBPHA also reduced the activation and expression of both MMP2 and MMP9 without altering the expression status of TIMP1 and TIMP2 in drug-resistant cancer. In addition, Sn-SBPHA reduced the activation of both STAT3 and JNK1, the transcriptional modulator of MMPs, in a redox-dependent manner in CEM/ADR5000 cells. Thus, Sn-SBPHA targets MMPs by modulating STAT3 and JNK1 in a redox-dependent manner. However, MBPHA and SBPHA fail to target drug resistance and both drug-resistant and sensitive cancer respectively. Furthermore, Sn-SBPHA significantly increases the lifespan of doxorubicin-resistant and sensitive Ehrlich Ascites Carcinoma-bearing mice without inducing any significant systemic toxicity. Therefore, Sn-SBPHA has the therapeutic potential to target and overcome MDR in cancer. [ABSTRACT FROM AUTHOR]

The compound 1, [(1H-[1]benzoxepino[5,4-c]pyrazole-3-carboxamide, 8-chloro-1-(2,4-dichlorophenyl)-4,5-dihydro-N-1-piperidinyl], a known CB1 modulator has been synthesized and characterized by IR, NMR and single Crystal X-ray study. The single crystal study of 1 displays a number of halogen bonds leading to 1-D network along with other weak noncovalent interactions. The CB1 modulator 1 inherently possesses extremely low solubility in water, which makes its application as drug difficult, and this may be attributed to multiple halogen bonds present in the crystal structure. A series of polymer additives, which are Generally Regarded As Safe (GRAS), have been explored to investigate whether they can modulate the halogen bond present in 1 through formation of various non-bonded interactions. Surprisingly, these polymers are found to change crystal morphology, crystal packing while retaining efficacy and bioavailability. The polymer molecular weight is found to play a significant role in crystal morphology modification especially in case of polyethylene glycol (PEG). The formation of new polymorphic forms of 1 and modification of halogen bond has been established using powder X-ray diffraction and IR study, respectively, in case of PEG 4000, PVPK-30, PVA polymers and compound 1 adducts. [ABSTRACT FROM AUTHOR]

Monte Carlo (MC) simulation is used to solve the eigenvalue form of the Boltzmann transport equation to estimate various parameters such as fuel pin flux distributions that are crucial for the safe and efficient operation of nuclear systems (e.g., a nuclear reactor). Monte Carlo eigenvalue simulation uses a sample mean over many stationary cycles (iterations) to estimate various parameters important to nuclear systems. A variance estimate of the sample mean is often used for calculating the confidence intervals. However, MC eigenvalue simulation variance estimators that ignore the intercycle correlation underestimate the true variance of the estimated quantity. This paper presents novel data-adaptive approaches based on a simple autoregressive (AR) model and sigmoid functions to improve MC variance estimation. The standard MC sample-based variance estimator (or naïve estimator) and the spectral density–based MC variance estimator are enhanced by adding data-adaptive components that reduce their bias and improve performance. By investigating the frequency pattern of the AR(1) (order 1) model, two adaptive spectral estimators and one adaptive naïve estimator are proposed. The proposed estimators manifest superior performance when applied to three test problems compared to the standard spectral density–based estimator previously introduced by the authors. These new estimators are straightforward, as they use online algorithms and do not require storage of tallies from all active cycles. [ABSTRACT FROM AUTHOR]

Simulations of neutron and photon transport using the Shift Monte Carlo radiation transport code are compared with experimental measurements and their corresponding benchmark simulations from several sets of experiments. Overall, Shift results match the calculations made by the benchmark teams quite well and match the measured values, which typically have large uncertainties, fairly well. A variety of attenuation/scattering problems are examined, as well as a streaming problem and a skyshine problem. [ABSTRACT FROM AUTHOR]

Background: Mycotoxins such as aflatoxins (AFs) and ochratoxin A (OTA) can pose severe health hazards because of their toxicity. Given a wide range of food matrices susceptible to fungal infections and possible cooccurrence of mycotoxins at different concentrations, validated multimycotoxin and multimatrix methods are strongly warranted. Objective: The aim of this research was to develop a simple and fast ultra-high performance LC (UHPLC) fluorescence detection (FLD)--based method to simultaneously determine AFs (B1, G1, B2, and G2) and OTA and, furthermore, to carry out singlelaboratory validation in a range of cereals and processed product matrices. Methods: The sample preparation involved homogenization and extraction with methanol--water (80 + 20). For cleanup, an aliquot (3 mL) was diluted with phosphate-buffered saline, loaded on an immunoaffinity column (AFLAOCHRA PREP®), and eluted with methanol (1 mL). The cleaned extract was diluted with 0.2% acetic acid (at a 1:1 ratio) before injection into an ultra-high performance liquid chromatograph. To perform simultaneous analysis of AFs and OTA, the FLD program was developed by switching the excitation wavelength in a single chromatographic run. Results: The method provided LOQs of 0.25 and 1 ng/g for AFs and OTA, respectively, without involving any derivatization. In rice, the recoveries of AFs ranged from 84 to 106%, whereas OTA had a recovery above 72%, with the repeatability relative SDs <12% for both analytes. The method was successfully applied to a range of naturally contaminated market samples. Conclusions: The method is suitable for regulatory testing because of its significant time and cost effectiveness and sensitivity in compliance with the regulatory maximum levels. Highlights: The study achieves high-throughput analysis of AFs and OTA in raw and processed cereals using simultaneous extraction, cleanup, and UHPLC-FLD. Method sensitivity complies with the regulatory maximum levels. Single-laboratory validation results meet analytical QC requirements. [ABSTRACT FROM AUTHOR]

Induction of undesired toxicity and emergence of multidrug resistance (MDR) are the major obstacles for cancer treatment. Moreover, aggressive cancers are less sensitive towards existing chemotherapeutics. Therefore, selective targeting of cancers without inducing undesired side effects and designing proper strategies to overcome MDR has utmost importance in modern chemotherapy. Previously we revealed the anticancer properties of some transition metal chelates of Schiff base, but the effectiveness of nickel complex is still unrevealed. Herein, we synthesized and characterized a Schiff base nickel chelate, nickel-(II) N-(2-hydroxyacetophenone) glycinate (NiNG), through different spectroscopic means. NiNG proves to be a broad spectrum anticancer agent with considerable efficacy to overcome MDR in cancer. Antiproliferative effects of NiNG was evaluated using drug-resistant (CEM/ADR5000; NIH-MDR-G185; EAC/Dox), drug-sensitive aggressive (Hct116; CCRF-CEM; EAC/S) and normal (NIH-3T3) cells that reveal the selective nature of NiNG towards drug resistant and sensitive cancer cells without inducing any significant toxicity in normal cells. Moreover, NiNG involves reactive oxygen species (ROS)-mediated redox imbalance for induction of caspase 3-dependent apoptosis in aggressive drug-sensitive Hct116 and drug-resistant NIH-MDR-G185 cells through disruption of mitochondrial membrane potential. Moreover, intraperitoneal (i.p.) application of NiNG at non-toxic doses caused significant increase in the life-span of Swiss albino mice bearing sensitive and doxorubicin-resistant subline of Ehrlich ascites carcinoma cells. It is noteworthy that, in vitro NiNG can only overcome P-glycoprotein-mediated MDR while in vivo NiNG can overcome MRP1-mediated MDR in cancer. Therefore, NiNG has therapeutic potential to target and overcome MDR in cancer. Graphical Abstract: [ABSTRACT FROM AUTHOR]

Monte Carlo (MC) methods have been widely used to solve eigenvalue problems in complex nuclear systems. Once a stationary fission source is obtained in MC simulations, the sample mean of many stationary cycles is calculated. Variance or standard deviation of the sample mean is needed to indicate the level of statistical uncertainty of the simulation and to understand the convergence of the sample mean. Current MC codes typically use sample variance to estimate the statistical uncertainty of the simulation and assume that the MC stationary cycles are independent. However, there is a correlation between these cycles, and estimators of the variance that ignore these correlations will systematically underestimate the variance. This paper discusses some statistical properties of the sample mean and the asymptotic variance and introduces two novel estimators based on (a) covariance-adjusted methods and (b) bootstrap methods to reduce the variance underestimation. For three test problems, it has been observed that both new methods can improve the estimation of the standard deviation of the sample mean by more than an order of magnitude. In addition, some interesting patterns were revealed for these estimates over the spatial regions, providing additional insights into MC simulations for nuclear systems. These new methodologies are based on post-processing the tally results and are therefore easy to implement and code agnostic. [ABSTRACT FROM AUTHOR]

Cancer chemotherapy suffers from selectivity and undesired toxicity of the drugs. Since zinc is a biocompatible tracer element and cysteine derivatives are used in cancer chemoprevention, we intend to develop a complex of zinc and cysteine-derivatives as potent, non-toxic anticancer agents. Herein, we synthesized and characterized cysteine based ligand, 2-[(2-Hydroxy-3-methoxy-benzylidene)-amino]-3-mercapto-propionic acid and its Zn-complex, which are found to be non-toxic towards normal human PBMC. Data also revealed that only Zn-complex exhibited remarkable apoptosis in drug-sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 cancer cells as assessed by MTT, Cell cycle and AnnexinV binding assay. Moreover, Zn-complex altered ROS and GSH level of the respective cell lines. Finally, treatment of Zn-complex in Swiss albino mice did not show any systemic toxicity in preliminary trials in normal mice and remarkably increased the life-span of EAC bearing mice. In conclusion, the synthesized Zn-complex may be developed for efficacious, multidrug resistance reversal, non-toxic chemotherapeutic agents in future. [ABSTRACT FROM AUTHOR]

The Used Nuclear Fuel-Storage, Transportation & Disposal Analysis Resource and Data System (UNF-ST&DARDS) methodology to perform automated containment analyses for potential transportation packages based on canister loading map information is described, and its capability is illustrated with example results. The allowable leakage rate is calculated with the procedures provided in ANSI N14.5-2014 and NUREG/CR-6487, which were adapted for containment analysis of a transportation package containing fuel assemblies with different nuclear characteristics (e.g., initial enrichment, burnup, and cooling time) and clad integrity (intact or damaged). UNF-ST&DARDS applies different source term calculation methodologies for low-burnup fuel (LBF) (i.e., <45 GWd/tonne U) assemblies and high-burnup fuel (HBF) (i.e., ≥45 GWd/tonne U) assemblies. The LBF radionuclide activities are based on actual fuel assembly burnup, initial enrichment, and cooling time. Bounding radionuclide activities based on a fuel pellet burnup value of 65 GWd/tonne U and actual fuel assembly cooling time are used for HBF assemblies. The fraction of failed fuel rods and the release fractions for the contributors to releasable source terms recommended in NUREG-1617 are used in the containment analysis regardless of fuel assembly burnup. However, UNF-ST&DARDS supports different parameter values for LBF and HBF assemblies. The containment analysis methodology for as-loaded transportation packages is presented in detail, and the UNF-ST&DARDS containment analysis capability is illustrated with results for simulated transportation packages containing spent nuclear fuel canisters in dry storage at selected sites. [ABSTRACT FROM PUBLISHER]

The Used Nuclear Fuel Storage, Transportation and Disposal Analysis Resource and Data System (UNF-ST&DARDS) is used to perform dose rate calculations for spent nuclear fuel (SNF) transportation packages based on the actual physical and nuclear characteristics (i.e., assembly design, burnup, initial enrichment, and cooling time) of the as-loaded SNF. Nuclear fuel data, transportation package model templates, and SNF canister loading map information residing within the tool facilitate automated generation of SCALE input files for radiation source term and dose rate calculations. Transportation package specific models developed for UNF-ST&DARDS dose rate analyses are described in detail. UNF-ST&DARDS dose rate analyses were performed for over 400 SNF canisters from 16 sites in their designated transportation casks. For simplicity, representative dose rate calculation results are presented as a function of time (i.e., selected calendar years between 2020 and 2100) for 73 SNF canisters in dry storage at four sites. For these canisters, the projected maximum dose rate values at 2 m from the lateral surfaces of the vehicle under normal conditions of transport (NCT) would vary between 1.9 and 11.5 mrem/h in 2020. Five SNF canisters will exceed the regulatory dose rate limit of 10 mrem/h at 2 m in 2020, and the analyzed SNF canisters will comply with regulatory dose rate limits by 2030. An analysis of the impact on the dose rate of fuel failure and reconfiguration during transportation indicated that the maximum dose rate for hypothetical accident conditions will be unaffected, and the NCT maximum dose rate at 2 m would have a maximum increase by a factor of 1.7 for a representative pressurized water reactor package and by a factor of 2.6 for a representative boiling water reactor package relative to intact fuel. Analysis of the actual heat loading and the dose rate at 2 m from the lateral surface of the vehicle for the five SNF canisters exceeding the NCT regulatory dose rate limit of 10 mrem/h in 2020 showed that the dose rate could be more limiting with respect to regulatory requirements than the heat loading; i.e., the canister transportability date may be evaluated based on the transportation package’s external dose rate. [ABSTRACT FROM PUBLISHER]

Vanadium compounds are well known for their therapeutic interventions against several diseases. Various biochemical attributes of vanadium complexes inspired us to evaluate the cancer cell killing efficacy of the vanadium complex, viz., vanadyl N-(2-hydroxyacetophenone) glycinate [VO(NG) 2 ]. Previously we showed that VO(NG) 2 is an effective anticancer agent in in vitro and in vivo cancer models and imposed miniscule side effects. Herein we report that VO(NG) 2 is significantly cytotoxic to various cancer cell lines. Furthermore, this redox active vanadyl complex altered the redox homeostatsis of many human cancer cell lines significantly. VO(NG) 2 actuates programmed cell death in human colorectal carcinoma cells(HCT-116) through mitochondrial outer membrane permeabilization but in caspase independent manner, possibly by altering cellular redox status and by inflicting DNA damage. Thus, the present work is an attempt to provide many evidences regarding the potent and selective chemotherapeutic efficacy of the novel VO(NG) 2 . [ABSTRACT FROM AUTHOR]

Background: Development of novel strategies to kill cancer by sparing normal cells is of utmost importance. Apart from their known antimicrobial activity, only limited information has been recorded regarding the antitumor potential of biocompatible silver oxide nanoparticles (AgONPs). There is a need to evaluate the anticancer potential of biocompatible AgONPs in vitro. Methods: A new approach of utilizing the leaf extract of Excoecaria agallocha was used to synthesize AgONPs. This was then characterized by ultraviolet-visible spectrophotometry, nanoparticle-tracking analysis, and ζ-potential analysis. Cytotoxicity and apoptotic potential were evaluated with an MTT assay and an annexin V-binding assay against the murine melanoma (B16F10), murine colon cancer (CT26), murine lung adenocarcinoma (3LL), and murine Ehrlich ascites carcinoma (EAC) cell lines. Cellular localization of AgONPs was evaluated on fluorescence microscopy. Results: UV peaks at 270 and 330 nm indicated the formation of nanoparticles (NPs) and the NP-tracking analyzer revealed them to have a size of 228 nm. AgONPs exerted initial cytotoxicity, specifically against all the experimental malignant cells by sparing the normal cell lines. Moreover, AgONPs exert apoptosis equally on all the malignant cells in vitro and ex vivo. This cytotoxicity possibly occurs via the nuclear translocation of AgONPs as analyzed in B16F10 cells. Conclusions: AgONPs utilizing natural sources would be a new medicinal approach against a broad spectrum of malignancy. [ABSTRACT FROM AUTHOR]

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of cancer and the therapeutic outcome for T-ALL patients remains poor. Thus innovative therapeutic strategies with less toxic drugs are of immense need. Moreover combinational effect of redox imbalance with modulated EGFR/PI3K/Akt axis in T-ALL is still elusive. To explore more effective drugs we developed and characterized 5-SMAG, Cu-5-SMAG and Cu-OBPHA complexes by different spectroscopic methods and revealed that introduction of methoxy group and copper to the previously synthesized Schiff base ligand, NG can efficiently target leukemia by sparing the normal cells and overcomes MDR in T-ALL through induction of caspase3 dependent apoptosis as assessed by MTT, Cell-cycle, Annexin-V and caspase3 activation assay. However the ligand 5-SMAG fails to exert significant cytotoxicity. Moreover introduction of copper does not increase the efficacy of the drug molecule as Cu-OBPHA fails to exert significant effect compared to Cu-5-SMAG. Moreover Cu-5-SMAG targets T-ALL cells more than Cu-OBPHA because Cu-5-SMAG generates greater extent of redox imbalance compared to Cu-OBPHA and when this redox imbalance is reduced by application of NAC and PEG-Catalase, highest abrogation of apoptosis is observed following Cu-5-SMAG treatment In addition, Cu-5-SMAG significantly down-regulates the activation and expression of EGFR1, Akt and PI3K in drug-resistant T-ALL cells. Furthermore Cu-5-SMAG significantly increases the life-span of doxorubicin resistant and sensitive Ehrlich ascites carcinoma bearing Swiss albino mice without inducing any significant systemic toxicity compared to 5-SMAG and Cu-OBPHA treatment. Therefore typical architect of Cu-5-SMAG made it a promising new anti-leukemic agent irrespective of the MDR phenotype. [ABSTRACT FROM AUTHOR]

A novel assessment has been completed to determine the unquantified and uncredited safety margins (i.e., the difference between the licensing-basis and as-loaded calculations) available in as-loaded spent nuclear fuel (SNF) casks. This assessment was performed as part of a broader effort to assess issues and uncertainties related to the continued safety of casks during extended storage and transportability following extended storage periods. Detailed analyses crediting the actual as-loaded cask inventory were performed for each of the casks at three decommissioned pressurized water reactor sites to determine their characteristics relative to regulatory safety criteria for criticality, thermal, and shielding performance. These detailed analyses were performed in an automated fashion by employing a comprehensive and integrated data and analysis tool--Used Nuclear Fuel-Storage, Transportation and Disposal Analysis Resource and Data System (UNF-ST&DARDS). Calculated uncredited criticality margins from 0.07 to almost 0.30 Δkeff were observed, calculated decay heat margins ranged from 4 to almost 22 kW (as of 2014), and significant uncredited transportation dose rate margins were also observed. The results demonstrate that at least for the casks analyzed here, significant uncredited safety margins are available that could potentially be used to compensate for SNF assembly and canister structural performance related uncertainties associated with long-term storage and subsequent transportation. The results also suggest that these inherent margins associated with how casks are loaded could support future changes in cask licensing to directly or indirectly credit the margins. Work continues to quantify the uncredited safety margins in the SNF casks loaded at other nuclear reactor sites. [ABSTRACT FROM AUTHOR]

BACKGROUND The pangasius catfish ( Pangasianodon hypophthalmus) is a ubiquitous item of seafood in global markets. However, pesticide residues in aquaculture fish, arising from agricultural run-off and/or direct application during pond preparation, pest control and harvest, are a potential food safety concern. This study assessed the level of chemical hazard in domestic and imported pangasius fish in India. RESULTS A total of 119 contaminants, including polyaromatic hydrocarbons ( PAHs), organochlorines ( OCs) and other groups of pesticides, were screened in 148 samples during 2014-2015 as the first endeavour of its kind in an Indian context, employing a validated gas chromatography/tandem mass spectrometry ( GC/ MS/ MS) method. Apart from the low-level incidence of OCs, pesticides such as quinalphos, malathion, parathion-methyl, etc. were detected in 38% of the samples. In comparison with Indian pangasius, fewer contaminants at low residue level were detected in pangasius fillets imported from Vietnam. CONCLUSION The human dietary exposures of the residue concentrations detected were less than the maximum permissible intakes and hence appeared safe. However, detection of commonly used pesticides indicated their direct application in aquaculture and contamination from agricultural run-off. This emphasizes the need for continual residue monitoring in aquaculture fish. © 2015 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) in cancer represents a variety of strategies employed by tumor cells to evade the beneficial cytotoxic effects of structurally different anticancer drugs and thus confers impediments to the successful treatment of cancers. Efflux of drugs by MDR protein-1, functional P-glycoprotein and elevated level of reduced glutathione confer resistance to cell death or apoptosis and thus provide a possible therapeutic target for overcoming MDR in cancer. Previously, we reported that a Schiff base ligand, potassium-N-(2-hydroxy 3-methoxy-benzaldehyde)-alaninate (PHMBA) overcomes MDR in bothin vivoandin vitroby targeting intrinsic apoptotic/necrotic pathway through induction of reactive oxygen species (ROS). The present study describes the synthesis and spectroscopic characterization of a copper chelate of Schiff base,viz., copper (II)-N-(2-hydroxy-3-methoxy-benzaldehyde)-alaninate (CuPHMBA) and the underlying mechanism of cell death induced by CuPHMBAin vitro. CuPHMBA kills both the drug-resistant and sensitive cell types irrespective of their drug resistance phenotype. The cell death induced by CuPHMBA follows apoptotic pathway and moreover, the cell death is associated with intrinsic mitochondrial and extrinsic receptor-mediated pathways. Oxidative stress plays a pivotal role in the process as proved by the fact that antioxidant enzyme; polyethylene glycol conjugated-catalase completely blocked CuPHMBA-induced ROS generation and abrogated cell death. To summarize, the present work provides a compelling rationale for the future clinical use of CuPHMBA, a redox active copper chelate in the treatment of cancer patients, irrespective of their drug-resistance status. [ABSTRACT FROM PUBLISHER]

The Indian industry has grown manifold since independence and today is ranked among the major global players. This has been a result of several factors which together have provided the right environment for India’s growth. However, given the fast pace of change, appropriate course corrections and suitable policy interventions are necessary for sustenance of future growth. In this paper, the authors present an argument rooted on innovativeness of Indian pharmaceutical industry to demonstrate how future growth possibilities can be created and sustained. Some of the challenges besieging the process have been identified as lack of skilled manpower, inadequate finances, low technological base and limited access to new technologies. The final results provide foundations of a business model having the potential of nurturing an innovative ecosystem in India in order to transform India into a producer of innovative pharmaceutical products. [ABSTRACT FROM AUTHOR]

Background: Multidrug resistance (MDR) is a major problem in cancer treatment. Cu complexes possess the ability to overcome MDR in cancer. Therefore, the search for new Cu complexes is of great clinical significance and we address the anticancer effects of a previously synthesized novel 9-phenyldibenzo[a,c]phenazin-9-ium cation [1+] as [1] [CuCl2] and as [1] [I]. Methods: The existence of the monovalent Cu(I) in [1] [CuCl2] was proven by electron paramagnetic resonance (EPR) studies and in vivo anticancer effects were studied in animals. Results: The monovalent nature of the Cu ion in [1] [CuCl2] was determined through EPR. The mean survival time of mice bearing doxorubicin-resistant Ehrlich ascites carcinoma cells is longer when [1] [I] is injected intraperitoneally whereas [1] [CuCl2] does not significantly increase the median survival in tumor-bearing mice. Compounds do not follow the immunomodulatory route and only [1] [I] shows cytotoxic activity in both MDR and drug-sensitive leukemia cell lines. Conclusion: An organic iodide complex rather than a cupric complex possesses direct cytotoxic potential. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A method was validated for the simultaneous analysis of the residues of dimethomorph, famoxadone and cymoxanil in grape and raisin matrix by ethyl acetate based extraction and liquid chromatography tandem mass spectrometric analysis. Field studies were conducted to evaluate the dissipation rate kinetics and processing factor (PF) for these pesticides during raisin making. Residue data during the drying process were best fitted to 1st + 1st order rate kinetics with half-life ranging between 8–9 days for dimethomorph, 12–13 days for famoxadone and 9–10 days for cymoxanil at single dose (SD) and double dose (DD), respectively. PF values calculated were 1.03 and 1.14 for dimethomorph, 1.95 and 2.09 for famoxadone, and 1.99 and 1.35 for cymoxanil at SD and DD, respectively. PF value >1 indicates concentration of the residues during raisin making. The residues of detected pesticides in market samples of raisins were devoid of any risk of acute toxicity related to dietary exposure. [ABSTRACT FROM AUTHOR]

Chemotherapeutics are the sole treatment modality for cancer patients at advanced condition. In the pursuit of getting an efficient, selective and non toxic anticancer agent that has not been discovered yet, we rationally synthesized a vanadium complex with a Schiff base ligand N -(-2-hydroxyacetophenone) glycinate. Characterization of the synthesized complex VO(NG) 2 , was carried out with the help of various spectroscopic means. The complex proved to be a broad spectrum anticancer agent with significantly less toxicity towards normal cells as evident from cell viability assay. Furthermore, VO(NG) 2 treatment increased the life-span of ascitic and solid tumor bearing Swiss albino mice and did not show any significant symptomatic sub acute toxicity on normal Swiss albino mice. [ABSTRACT FROM AUTHOR]

Abstract: Anticancer drugs induce apoptosis to cancer cells and also exhibit undesired toxicity to normal cells. Therefore development of novel agents triggering apoptosis and have low toxicity towards normal cells is most important. Hydroxamic acids suppress tumour cell growth through apoptosis but the underlying mechanism is poorly understood. Herein, we describe the apoptotic potential of a dibasic hydroxamic acid derivative, viz., oxayl bis (N-phenyl) hydroxamic acid (OBPHA), which induces apoptosis through generation of both ROS and NO in doxorubicin resistant T-lymphoblastic leukemia, CEM/ADR5000 cells. Present study discloses that OBPHA selectively kills cancerous cells irrespective of their drug resistant phenotype. We also determined the crystal structure of OBPHA to understand the structural requirements for apoptosis; the study reveals that the presence of substituted hydroxamic acid groups (–CO–NH–OH) favours the generation of NO possibly through auto degeneration. Along with the induction of caspase 3 mediated intrinsic apoptosis; OBPHA also activates p53 dependent signalling cascade and downregulates HDAC3 expression in a time dependent manner possibly due to increased ROS and NO production and simultaneous decrease in cellular GSH level. Thus ROS and NO mediated downstream signalling are essential for the anticancer effect of OBPHA. Therefore OBPHA, having a structurally relevant pharmacophore provides important insight into the development of new ROS and RNS generating chemicals inducing p53 dependent apoptosis. [Copyright &y& Elsevier]

Highlights: [•] Dissipation kinetics of the residues of CPPU, 6-BA, GA3 and Ethephon in grape are reported. [•] Dissipation of residues followed 1st +1st order kinetics. [•] Initial residue of GA3 was below MRL and hence no pre-harvest interval (PHI) is applicable. [•] CPPU, 6-BA and Ethephon residues dissipated with PHIs of 33.5, 12 and 32days, respectively. [Copyright &y& Elsevier]

Abstract: Multidrug resistance (MDR) remains a significant problem for effective cancer chemotherapy. In spite of considerable advances in drug discovery, most of the cancer cases still stay incurable because of resistance to chemotherapy. We synthesized a novel, Mn (II) complex (chelate), viz., manganese N-(2-hydroxy acetophenone) glycinate (MnNG) that exhibits considerable efficacy to overcome drug resistant cancer. The antiproliferative activity of MnNG was studied on doxorubicin resistant and sensitive human T lymphoblastic leukemia cells (CEM/ADR 5000 and CCRF/CEM). MnNG induced apoptosis significantly in CEM/ADR 5000 cells probably through generation of reactive oxygen species. Moreover, intraperitoneal (i.p.) application of MnNG at non-toxic doses caused significant increase in the life-span of Swiss albino mice bearing sensitive and doxorubicin resistant subline of Ehrlich ascites carcinoma cells. [Copyright &y& Elsevier]

Abstract: A single quadrupole GC–MS method was optimized for multiresidue determination of 47 pesticides in grapes with limit of quantifications of each compound in compliance with the EU-MRL requirements. Sample preparation involved extraction of 10g sample with 10ml ethyl acetate (+10g sodium sulphate) by homogenization at 15,000rpm followed by centrifugation at 3000rpm. The supernatant was cleaned by dispersive solid phase extraction with primary secondary amine and acidified with 0.1% formic acid. Residues were estimated in selected ion monitoring mode with programmable temperature vaporizer-large volume injection (8μl). All the GC and MS parameters were thoroughly optimized to achieve satisfactory linearity (R 2 >0.99) within 0.01–0.25mgkg−1 with minimum matrix interferences. Recoveries at 0.01 and 0.02mgkg−1 were within 67–120% with associated precision RSD below 19%. The method was successfully applied for analysis of the real world samples for incurred residues. [Copyright &y& Elsevier]

Abstract: A residue analysis method for the simultaneous estimation of 349 pesticides, 11 PCBs and 15 PAHs extracted from grape, pomegranate, okra, tomato and onion matrices, was established by using a gas chromatograph coupled to an electron impact ionization triple quadrupole mass spectrometer (GC–EI-MS/MS). The samples were extracted by ethyl acetate and cleaned by dispersive solid phase extraction with PSA and/or GCB/C18 by the methods reported earlier. The GC–EI-MS/MS parameters were optimized for analysis of all the 375 compounds within a 40min run time with limit of quantification for most of the compounds at <10μg/L, which is well below their respective European Union-Maximum Residue Levels. The coefficient of determination (r 2) was >0.99 within the calibration linearity range of <5–250ng/mL for compounds with LOQs<5ng/mL. While for the compounds with LOQs within 5–10μg/kg, the lowest calibration level was 5 and 10μg/kg as applicable. The recoveries at 10, 25 and 50ng/mL were within 70–110% (n =6) with associated RSDs<20% indicating satisfactory precision. The information generated from the single laboratory validation was further utilized for building a semi-quantitative approach. The accuracies in quantification obtained via individual calibration standards vis-à-vis semi-quantification approach were comparable. For incurred samples, the concentrations estimated by the semi-quantification approach were within ±10% of the values obtained by direct quantification. This approach complements the existing GC–EI-MS/MS methods by offering targeted screening and quantification capabilities. [Copyright &y& Elsevier]

Chlorimuron-ethyl, ethyl-2-[[[[(4-methoxy-6-chloro-pyrimidin-2-yl)amino]carbonyl]amino] sulfonyl]benzoate, is used as a pre- and postemergence herbicide for the control of important broadleaved weeds in soybean and maize. Due to its phytotoxicity to rotation crops, concerns regarding chlorimuron contamination of soil and water have been raised. Although it is degraded in the agricultural environment primarily via pH- and temperature-dependent chemical hydrolysis, microbial transformation also has an important role. Fungi such as Fusarium and Alternaria are unable to survive in artificial media containing chlorimuron-ethyl at 25 mg L−1. However, Aspergillus niger survived in minimal broth containing chlorimuron at 2 mg mL−1. Aspergillus niger degraded the herbicide to harvest energy through two major routes of degradation. One route involves the cleavage of the sulfonylurea bridge, resulting in the formation of two major metabolites, namely ethyl-2-aminosulfonylbenzoate ( I) and 4-methoxy-6-chloro-2-amino-pyrimidine ( II). The other route is the cleavage of sulfonylamide linkage, which generates the metabolite N-(4-methoxy-6-chloropyrimidin-2-yl) urea ( III). Two other metabolites, saccharin ( IV) and N-methyl saccharin ( V), formed from metabolite II, were also identified. A metabolic pathway for the degradation of chlorimuron-ethyl by A. niger has been proposed. [ABSTRACT FROM AUTHOR]

This paper reports the bioefficacy of selected insecticides against thrips and their pre-harvest intervals (PHI) in onion pertaining to their recommended application rates and maximum residue limits. Profenophos, methomyl and imidacloprid showed comparatively higher bioefficacy against thrips. GC-MS and LC-MS/MS-based residue analysis methods in onion bulbs and composite matrix of bulbs+leaves were thoroughly validated. The residue data for bulb+leaves was assessed with reference to the EU-MRLs applicable for spring onion. Dimethoate was the most stable chemical with PHI of 52.5 days, followed by monocrotophos (24 days) and carbofuran (20.5 days). The PHIs of profenophos, chlorpyrifos, methomyl and cypermethrin were similar and within the range of 10–13 days. Imidacloprid and λ-cyhalothrin had similar PHI of 4.5 days. Spinosad was the fastest-degrading chemical with PHI of 2 days. The combined bioefficacy and residue dynamics information will support label-claim of these insecticides for the management of thrips in onion, help in scheduling their applications in pest management program as per relative PHIs and minimize the residue accumulations at harvest. The dietary exposure was less than the maximum permissible intake for most of the insecticides on all sampling days except for dimethoate and monocrotophos. [ABSTRACT FROM PUBLISHER]

The concept of Industrial relations and Labour Welfare had been changing gradually after 1991. The modern era is characterized by the demise of manufacturing, the growth of service sector, globalization of market, revolution in information technology, labour and capital mobility, subcontracting and use of contract labour that poses a challenge to restructure the legal environment of business. This empirical study tries to find out the application of labour welfare in different manufacturing and service organizations. A total sample size of 285 participants from 19 different organizations is taken. Among these, 8 organizations are big production houses like Stone India Limited, Paharpur Cooling Towers, Calcutta Port Trust, Pulver Ash Limited, Burn Standard, Tata International Limited, Modern Bakeries and Mescab Cables; and 11 organizations are service sectors like West Bengal Board of Secondary Education, Bank of India, UCO Bank, Kolkata Metropolitan Corporation, Life Insurance Corporation of India, State Bank of India, Calcutta Medical and Research Institute, Kolkata Police, Calcutta Electric Supply Corporation, Bajaj Allianz and Renaul Technologies. Questionnaire method is used for primary data collection. In the questionnaire, two major areas - statutory and non-statutory welfare amenities are taken into consideration. Under statutory welfare amenities eight different welfare criteria which are binding on organizations through statutes are considered. Likert scale (5-point) for answering alternatives (outstanding - 5, good - 4, fair - 3, poor - 2, unsatisfactory - 1) is applied for scoring. The t-test is applied to find out acceptance/rejection of hypothesis (Hypothesis-I: Statutory welfare amenities are properly applied in big production houses). Similarly, under non statutory welfare amenities twelve categories are considered. These categories are not binding on organizations. Likert scale is again applied for scoring purpose. The t-test is applied to test the hypothesis (Hypothesis-II: Non statutory welfare amenities are not properly applied in big production houses and service organizations). The results show that in big production houses, average scores of Managers, Supervisors and Workers on statutory welfare amenities are more than fair values. But average scores of Managers, Supervisors & Workers on non-statutory welfare amenities are less than fair values. Correlation co-efficient among Managers & Workers, Managers & Supervisors and Supervisors & Workers on statutory welfare amenities are close to 1. Correlation on non-statutory welfare amenities between Managers & Workers is positive but in 25% cases it is around or below 0.5. The t-test results on average scores of Managers, Supervisors and Workers on statutory welfare amenities show that they are not significantly different. The t-test result on average scores of deviations on non statutory welfare amenities between Managers & Supervisors is not significantly different but in between Managers & Workers and Supervisors & Workers are significantly different. This shows either the workers do not have proper idea on non statutory welfare amenities they are receiving from the company, or the managers may not help them understanding the company policies on non statutory welfare measures in big production houses and this creates perceptual difference between Managers & Workers on non-statutory welfare amenities. In service organizations, average scores of Managers, Supervisors & Workers on non-statutory welfare amenities are less than fair values. The t-test results on average score of Managers, Supervisors and Workers on non-statutory welfare amenities are not significantly different. Hypothesis- I is accepted as most of the big production houses are giving proper statutory welfare amenities. Hypothesis-II is accepted as most of the big production houses and service organizations are not giving proper non-statutory welfare amenities. [ABSTRACT FROM AUTHOR]

Abstract: Food safety aspects of buprofezin, dimethoate and imidacloprid residues in pomegranate are reported. The residue analysis involved extraction of samples (15g) with 10ml ethyl acetate, cleanup by dispersive solid phase extraction with 25mg primary secondary amine and 25mg C18 sorbents and estimation by LC–MS/MS. The limit of quantification of each analyte was 0.001mgkg−1 with recoveries within 76–109%. The residues of buprofezin and dimethoate were confined to outer rind, which degraded to below the maximum residue limit for the European Union (EU-MRL) after 10.5 and 31.5days at standard dose and 32.0 and 44.0days at double dose. Residues of imidacloprid penetrated into the albedo and membrane, although at less than the MRL in all samples even at double dose. The dietary exposure of buprofezin and imidacloprid was safe on all sampling days; whereas samples with dimethoate appeared safe after 15 and 30days of field applications at standard and double doses, respectively. [Copyright &y& Elsevier]

The article presents a multiresidue analysis of plant growth regulators (PGRs) in grapes by triple quadrupole and quadrupole-time-of-flight- (Q-TOF) based liquid chromatography/mass spectrometry (LC/MS). It finds that an accurate mass-based screening and identification of 12 PGRs with the Q-TOF mass spectrometer could be done without sacrificing sensitivity. It concludes that the method could determine all 12 PGRs by a single method with quantification by MS/MS and confirmation by Q-TOF-MS.

Abstract: An aqueous extraction method coupled with ultra performance liquid chromatography with photo diode array detection was optimised and validated for screening of 93 garlic ecotypes for allicin and other allyl thiosulphinate contents. Variability in allicin, allyl methyl thiosulphinate and allyl trans-1-propenyl thiosulphinate was observed both on fresh and dry weight basis. Bulb to bulb variation for allicin levels was less in clonal selections followed by commercial varieties, exotic line and landraces, respectively. Five ecotypes on fresh weight basis and all the ecotypes on dry weight basis had allicin contents more than the recommended pharmacological values (⩾4.5mgg−1). Cluster analysis and principal component analysis results revealed that geographical origin, breeding status and colour did not play any role in ecotype clustering. This study is useful as a base for selection of garlic ecotypes as a dependable raw material source for pharmaceutical and food processing industries. [Copyright &y& Elsevier]

Abstract: Water based samples such as flavored drinks, juices and drinking water may contain contaminants at ultra trace level belonging to different chemical classes. A novel, simple, low-cost and fast method was developed and validated for trace residue extraction of pesticides, dioxin-like PCBs and PAHs from water and water based samples followed by analysis through gas chromatography (GC) coupled with time-of-flight mass spectrometry (ToFMS). The extraction solvent type, volume; sample volume and other extraction conditions were optimized. This was achieved by extracting 10mL sample with 250μL chloroform by vortexing (1min, standing time of 2min) followed by centrifugation (6000rpm, 5min). The bottom organic layer (200μL) was pipetted out, evaporated to near dryness and reconstituted in 20μL of ethyl acetate+cyclohexane (1:9) mixture resulting in an enrichment factor of 400. The recoveries of all compounds were within 76–120% (±10%) with the method detection limit (MDL) ranging from 1 to 250ng/L depending on the analyte response. The MDLs were 400 times lower than the instrument quantification limits that ranged from 0.4 to 100ng/mL. The method was further validated in water based drinks (e.g. apple, lemon, pineapple, orange, grape and pomegranate juice). For the juices with suspended pulp, the extraction was carried out with 400μL chloroform. The extract was analyzed by GC-ToFMS at both 1D and GC×GC modes to chromatographically separate closely eluting interfering compounds the effect of which could not be minimized otherwise. The resulting peak table was filtered to identify a range of compounds belonging to specific classes viz. polycyclic aromatic hydrocarbons, chlorinated, brominated, and nitro compounds. User developed scripts were employed on the basis of identification of the molecular ion and isotope clusters or other spectral characteristics. The method performed satisfactorily in analyzing both incurred as well as market samples. [Copyright &y& Elsevier]

Abstract: Multidrug resistance (MDR) mediated by the over expression of drug efflux protein P-glycoprotein (P-gp) is one of the major impediments to successful treatment of cancer. P-gp acts as an energy-dependent drug efflux pump and reduces the intracellular concentration of structurally unrelated drugs inside the cells. Therefore, there is an urgent need for development of new compound that are less toxic and effective against drug resistance in cancer. Preclinical studies have shown that quinoline derivatives possess anticancer activities. Here, we report the antitumor potential of quinoline derivative, 2-(2-Methyl-quinolin-4ylamino)-N-phenyl acetamide (S4). To evaluate the cytotoxic potential of S4, we used four different cell lines (Hela, HCT-116, CCRF-CEM, and CEM/ADR 5000) in vitro, and showed that S4 kills doxorubicin resistant T lymphoblastic leukemia cell, CEM/ADR 5000 in a concentration dependent manner while others remains unaffected. Moreover, S4 induces apoptosis in CEM/ADR 5000 cells through generation reactive oxygen species (ROS). This is substantiated by the fact that the antioxidant N-acetyle-cysteine (NAC) completely blocks ROS generation and, subsequently, abrogates S4 induced apoptosis. Furthermore, in vivo treatment with S4 significantly increases the life span of swiss albino mice bearing sensitive and doxorubicin resistant subline of Ehrlich ascites carcinoma. In addition, intraperitoneal application of S4 in mice does not show any systemic toxicity at concentrations that in preliminary trials in a mice Ehrlich ascites carcinoma model. Therefore, present report provides evidence that S4, a quinoline derivative, may be a promising new therapeutic agent against drug resistant cancers. [Copyright &y& Elsevier]

Abstract: A novel method for the residue analysis of wine spoilage compound 2,4,6-trichloroanisole is reported. Wine (60ml) was extracted with 2ml toluene in presence of 24g MgSO4 and 6g NaCl. Cleanup of the toluene phase by dispersive solid phase extraction with mixture of 100mg CaCl2, 25mg primary secondary amine and 50mg MgSO4 was effective in minimising co-extractives and matrix effects. Time-of-flight and tandem mass spectrometric parameters were optimised to achieve linearity over 0.25–500ngml−1 and method detection limit 0.0083ngml−1 which is well below the odour threshold of 0.04ngml−1. Recoveries at 0.04, 0.2 and 0.8ngml−1 were within 80–110% (±8%). The method was reproducible when tested for Argentinean wines with intra-laboratory Horwitz ratios being <0.20 in white and red wines at both the laboratories of India and Argentina. The method could be successfully applied for incurred wine samples. [ABSTRACT FROM AUTHOR]

Abstract: Two-dimensional gas chromatography (GC×GC) coupled with time-of-flight mass spectrometric (TOFMS) method was optimized for simultaneous analysis of 160 pesticides, 12 dioxin-like polychlorinated biphenyls (PCBs), 12 polyaromatic hydrocarbons (PAHs) and bisphenol A in grape and wine. GC×GC–TOFMS could separate all the 185 analytes within 38min with >85% NIST library-based mass spectral confirmations. The matrix effect quantified as the ratio of the slope of matrix-matched to solvent calibrations was within 0.5–1.5 for most analytes. LOQ of most of the analytes was ≤10μg/L with nine exceptions having LOQs of 12.5–25μg/L. Recoveries ranged between 70 and 120% with <20% expanded uncertainties for 151 and 148 compounds in grape and wine, respectively, with intra-laboratory Horwitz ratio <0.2 for all analytes. The method was evaluated in the incurred grape samples where residues of cypermethrin, permethrin, chlorpyriphos, metalaxyl and etophenprox were detected at below MRL. [Copyright &y& Elsevier]

Abstract: A multiresidue method is described for simultaneous estimation of 83 pesticides and 12 dioxin-like polychlorinated biphenyls (PCBs) in red and white wines. The samples (20mL wine, acidified with 20mL 1% HCl) were extracted with 10mL ethyl acetate (+20g sodium sulphate) and cleaned by dispersive solid-phase extraction (DSPE) with anhydrous calcium chloride and Florisil successively. The final extract (5mL) was solvent exchanged to 1mL of cyclohexane:ethyl acetate (9:1), further cleaned by DSPE with 25mg primary secondary amine sorbent and analyzed by gas chromatography–time-of-flight mass spectrometry (GC–TOF-MS) within 31min run time. The limits of quantification of most analytes were ≤10–20μg/L. Acidification of wine prior to extraction prevented hydrolysis of organophosphorous pesticides as well as dicofol, whereas treatment with CaCl2 minimized the fatty acid co-extractives significantly. Solvent exchange to cyclohexane:ethyl acetate (9:1) further minimized the co-extractives. Recoveries at 5, 10 and 20ng/mL were >80% for most analytes except cyprodinil, buprofezin and iprodione. The expanded uncertainties at 10ng/mL were <20% for most analytes. Intra-laboratory precision in terms of Horwitz ratio of all the analytes was below 0.5, suggesting ruggedness of the method. Effectively, the method detection limit for most analytes was as low as up to 1ng/mL in both red and white wine, except for cyfluthrin and cypermethrin. [Copyright &y& Elsevier]

Abstract: A comprehensive GC×GC–TOFMS method was optimized for multiresidue analysis of pesticides using a combination of a non-polar (RTX-5MS, 10m×0.18mm×0.2μm) and a polar capillary column (TR-50MS, 1m×0.1mm×0.1μm), connected in series through a dual stage thermal modulator. The method resolved the co-elution problems as observed in full scan one-dimensional GC–MS analysis and allowed chromatographic separation of 51 pesticides within 24min run time with library-searchable mass spectrometric confirmation. Four pesticides, viz. chlorpyrifos-methyl, vinclozoline, parathion-methyl and heptachlor could be baseline separated on GC×GC, which were otherwise closely eluting and interfering each other''s detection in 1D GC–MS run. Similarly, it could be possible to separate myclobutanil, buprofezin, flusilazole and oxyfluorfen on GC×GC. Although in 1D GC–MS, these closely eluting compounds could be identified through deconvolution algorithm and ‘peak-find’ option of the Chromatof® software but the spectral purity significantly improved on GC×GC analysis. Thorough optimization was accomplished for the oven temperature programming, ion source temperature and GC×GC parameters like modulation period, duration of hot pulses, modulation-offset temperature, acquisition rate, etc. to achieve best possible separation of the test compounds. The limit of detection significantly improved by 2–12 times on GC×GC–TOFMS against GC–TOFMS because of sharper and narrower peak shapes. The method was tested for grape matrix after preparing the samples using previously described method and recoveries of the entire test pesticides were within 70–110% at 10ng/g level of fortification. GC×GC–TOFMS was found to be an excellent technique for library-based screening of pesticides with high accuracy and sensitivity. [Copyright &y& Elsevier]

The rate of degradation of forchlorfenuron, a cytokinin-based plant growth regulator (PGR) was explored in typical grapevine soils of India with simultaneous evaluation of its effect on biochemical attributes of the test soils in terms of the activities of specific soil microbial enzymes. In all the test soils, namely clay, sandy-loam and silty-clay, the dissipation rate was faster at the beginning, which slowed down with time, indicating a non-linear pattern of degradation. Degradation in soils could best be explained by two-compartment 1st + 1st order kinetics with half-life ranging between 4-10 days. The results suggest that organic matter might be playing a major role in influencing the rate of degradation of forchlorfenuron in soil. The rate of degradation in sandy-loam soil was fastest followed by clay and silty-clay soils, respectively. Comparison of the rate of degradation in natural against sterilized soils suggests that microbial degradation might be the major pathway of residue dissipation. Changes in soil enzyme activities as a consequence of forchlorfenuron treatment were studied for extra-cellular enzymes namely acid phosphatase, alkaline phosphatase and β -glucosidase and intracellular enzyme-dehydrogenase. Although small changes in enzyme activities were observed, forchlorfenuron did not have any significant deleterious effect on the enzymatic activity of the test soils. Simple correlation studies between degradation percentage and individual enzyme activities did not establish any significant relationships. The pattern and change of enzyme activity was primarily the effect of the incubation period rather than the effect of forchlorfenuron itself. [ABSTRACT FROM AUTHOR]

The sorption behavior of the insecticide thiamethoxam [3-(2-chloro-1,3-thiazol-5-ylmethyl)-5-methyl-1,3,5-oxadiazinan-4-ylidene(nitro)amine] on three Indian soils with different physico-chemical properties was investigated. The soils represent the major grapevine growing areas of India, where the vineyards frequently receive thiamethoxam applications as foliar spray, soil drenching and through drip irrigation for the management of various insect pests. The rate constants for adsorption and desorption at two different temperatures were obtained from the Lindstrom model, which simultaneously evaluated adsorption and desorption kinetics. The data for rate constants, activation energies, enthalpy of activation, entropy of activation and free energy indicated physical adsorption of thiamethoxam on soil. The adsorptivity of different soils might be attributed to the organic matter and clay contents. A good fit to the linear and Freundlich isotherms was observed for both adsorption as well as desorption. Thiamethoxam could be categorized as a chemical with medium leaching potential. [ABSTRACT FROM AUTHOR]

Abstract: A method was validated for the multi-residue analysis of 82 pesticides in grapes at ≤25ng/g level. Berry samples (10g) mixed with sodium sulphate (10g) were extracted with ethyl acetate (10mL); cleaned by dispersive solid phase extraction and the results were obtained by liquid chromatography–tandem mass spectrometry. Reduction in sample size and proportion of ethyl acetate for extraction did not affect accuracy or precision of analysis when compared to the reported methods and was also statistically similar to the QuEChERS technique. The method was rugged (HorRat<0.5) with <20% measurement uncertainties. Limit of quantification was <10ng/g with recoveries 70–120% for most pesticides. The method offers cheaper and safer alternative to typical multi-residue analysis methods for grape. [Copyright &y& Elsevier]

Four geometric isomers of trifloxystrobin (TFS)—namely EE, EZ, ZE, and ZZ—were hydrolyzed by 0.05 M NaOH, resulting in four corresponding acid metabolites. These compounds—namely EE-, EZ-, ZE-, and ZZ-acids—were purified by preparative HPLC and authentically characterized by a combination of infrared, Raman, GC–MS, LC–MS/MS, and NMR spectroscopies. The spectra were found to be very characteristic of the individual isomers, and so they could be used to distinguish the isomers from each other. The detailed spectral features of the individual isomers are presented and compared. EE-acid was identified as being the major metabolite of TFS in soil, which indicates that hydrolysis is the principal route of degradation of TFS. This finding further justifies the importance of the present study in relation to assessing the risk associated with the release of TFS into the environment. [ABSTRACT FROM AUTHOR]

Rates of degradation of λ-cyhalothrin and methomyl residues in grape are reported. The dissipation behavior of both insecticides followed first-order rate kinetics with similar patterns at standard and double-dose applications. Residues of λ-cyhalothrin were lost with pre-harvest intervals (PHI) of 12.0–12.5 and 15.0–15.5 days, corresponding to the applications at 25 and 50&ThickSpace;g a.i. ha -1 , respectively. In the case of methomyl, residues were lost with PHI of 55.0 and 61.0 days, following applications at 1 and 2&ThickSpace;kg a.i. ha -1 , respectively. The PHI, recommended on the basis of the experimental results, was shown to be effective in minimizing residue load of these insecticides below their maximum residue limits (MRLs) in vineyard samples. [ABSTRACT FROM AUTHOR]

The photoisomerization kinetics of trifloxystrobin (TFS) in acetone under artificial sunlight is reported. HPLC analysis showed the TFS, a strobilurine fungicide of EE conformation, was converted into an equilibrium mixture of four isomers after illumination for 7 h. The isomers were identified as EZ, EE, ZZ, and ZE and were separated in the crystalline form by preparative HPLC and characterized by use of a variety of spectroscopic techniques. The quantum yield and reaction constants for the isomerization reactions were determined. The detailed spectral features of the individual isomers measured by UV, IR, Raman, NMR and mass spectroscopy are presented and compared. The spectra of the isomers were found to be very characteristic, with good analytical significance. [ABSTRACT FROM AUTHOR]

The residue dynamics of carbendazim and mancozeb in grape berries is reported. The fungicides were sprayed in accordance with the most critical use pattern i.e. 4 times at 15 days interval separately at recommended and double doses. The residues of each fungicide dissipated following 1st order rate kinetics. The half-lives of carbendazim and mancozeb were 7.3 and 8.1 days at recommended dose and 4.6 and 5.7 days at double dose. Ethylenethiourea (ETU), the toxic metabolite of mancozeb was detectable at harvest following four sprays of mancozeb at recommended dose. At double dose, however, the residues of ETU could be detected even after three sprays of mancozeb. The pre-harvest intervals for carbendazim and mancozeb were found to be 26 and 12 days at recommended dose and 33 and 17 days at double dose, respectively. [ABSTRACT FROM AUTHOR]

Objective Vaccine-associated paralytic poliomyelitis (VAPP) is a rare but serious consequence of the administration of oral polio vaccine (OPV). Intensified OPV administration has reduced wild poliovirus transmission in India but VAPP is becoming a matter of concern. Methods We analysed acute flaccid paralysis (AFP) surveillance data in order to estimate the VAPP risk in this country. VAPP was defined as occurring in AFP cases with onset of paralysis in 1999, residual weakness 60 days after onset, and isolation of vaccine-related poliovirus. Recipient VAPP cases were a subset with onset of paralysis between 4 and 40 days after receipt of OPV. Findings A total of 181 AFP cases met the case definition. The following estimates of VAPP risk were made: overall risk, 1 case per 4.1 to 4.6 million OPV doses administered; recipient risk, 1 case per 12.2 million; first-dose recipient risk, 1 case per 2.8 million; and subsequent-dose recipient risk, 1 case per 13.9 million. Conclusion On the basis of data from a highly sensitive surveillance system the estimated VAPP risk in India is evidently lower than that in other countries, notwithstanding the administration of multiple OPV doses to children in mass immunization campaigns. [ABSTRACT FROM AUTHOR]

Examines the acute flaccid paralysis (AFP) surveillance strategy used in India for polio eradication. Deployment of Surveillance Medical Officers for active AFP surveillance; Reports of AFP occurrences; Timely case investigations and collection of stool specimens; Linkages to support polio laboratory network; Training of government surveillance officers; Impact of the strategy.