Pagetoid Squamous Cell Carcinoma In-Situ of Esophagus.

Squamous cell carcinoma (SCC) is the most common malignant tumor of the esophagus, however, pagetoid SCCIS is an extremely rare condition in esophagus.1 Pagetoid Squamous Cell Carcinoma In-Situ (SCCIS) has been described in skin and external genitalia frequently.2 Herein we report a case of pagetoid squamous cell carcinoma in-situ in a 50-year-old male with clinical information, histopathological and immunohistochemical findings. The patient was a 50 years male with dyspepsia,refractory to proton pump inhibitors (PPIs). In upper gastroduodenal endoscopy, there was no obvious lesion in the esophagus and only mild erythema was noted. Biopsy showed a surprising finding of full thickness high grade squamous dysplasia in the lining squamous epithelium with scattered single large atypical cells. These cells were present away from the foci of dysplasia. The cells were large and showed marked pleomorphism, vesicular nuclei, prominent nucleoli and abundant pale to eosinophilic cytoplasm. Immunohistochemistry (IHC) was positive for p63 and p53, which confirmed the diagnosis of pagetoid SCCIS. Pagetoid squamous cell carcinoma in-situ is one of the rare entities with subtle clinical presentation and endoscopic findings. Evaluation of this case signifies the importance of taking biopsies in the lesions which shows minimal mucosal change in the endoscopy.

Elemental composition of aquaculture fish from West Bengal, India: nutrition versus food safety.

Aquaculture production continues to grow in West Bengal, where on average people consume 8.2 kg capita-1 of fish each year, and an extensive mosaic of aquaculture ponds has developed along the River Hugli as clay pits are repurposed. The adjacent brickworks and industry (especially tanneries) are a source of environmental pollution, with potential for bioaccumulation of potentially harmful elements (PHEs) in fish farmed in these ponds. Fish from aquaculture present an opportunity to meet food sufficiency in West Bengal; however, an investigation to assess their effectiveness for micronutrient supply balanced against food safety is required. Five ponds close to industrial brick manufacture (urban) and three from rural areas were assessed for the degree of pollution within their pond sediments and waters. Fish were also sampled from each location including a subset from the market in Kolkata to determine the concentrations of PHEs in their fish muscle tissue. Dietary intake and PHE loading were calculated for four fish species to evaluate their nutrient content with respect to recommended daily intakes for adults, e.g. calcium (Ca), potassium (K), magnesium (Mg), iron (Fe), zinc (Zn) and selenium (Se), and to establish whether the provisional maximum tolerable intakes (PMTIs) are exceeded for PHEs, e.g. aluminium (Al), arsenic (As), mercury (Hg), chromium (Cr), tin (Sn), copper (Cu) and lead (Pb). Preliminary results suggest that aquaculture is making an important contribution to nutrition, with fish being a good source of Se. However, in contrast to small wild-caught fish, aquaculture fish in the present study were poor sources of Fe, Ca and Zn. The fish also made substantial contributions (> 10%) to the PMTI of Hg and As. Therefore, there is an urgent need for ongoing monitoring and an expanded sampling programme, as well as research into approaches which might improve the nutritional quality of the farmed fish.

Magnetic Resonance Imaging and the Use in Small Renal Masses.

The incidence of small renal masses (SRM) has been increasing, and this is mainly attributed to the incidental finding of such masses on imaging performed in asymptomatic patients. Consequently, this calls for careful evaluation and management of these masses to determine their nature and need for treatment. This article reviews current literature regarding the evaluation and management of SRM. It focuses on the specific use of MRI in the diagnosis and management of SRM. A Medline review of the literature was performed from 1996 to the present time. Computed tomography (CT) imaging has been the investigation of choice for evaluating SRM. However, some remain difficult to determine their malignant or benign nature and remain indeterminate. In such cases, further imaging with magnetic resonance imaging (MRI) can be performed to evaluate the mass in more detail. It can also be used where CT is contraindicated and where active surveillance is the treatment of choice and radiation exposure is a concern. MRI is a useful tool in evaluating an indeterminate small renal mass. Accurate diagnosis and management of SRM require close collaboration between a urologist and radiologist to identify potentially malignant tumours to subsequently reduce mortality from renal cell cancer.

Impact of silver nanoparticles on benthic prokaryotes in heavy metal-contaminated estuarine sediments in a tropical environment.

Little knowledge is available about the potential impact of commercial silver nanoparticles (Ag-NPs) on estuarine microbial communities. The Hugli river estuary, India, is susceptible to heavy metals pollution through boat traffic, and there is the potential for Ag-NP exposure via effluent discharged from ongoing municipal and industrial activities located in close proximity. This study investigated the effects of commercial Ag-NPs on native microbial communities in estuarine sediments collected from five stations, using terminal restriction fragment length polymorphism (T-RFLP) technique. An increase in the number of bacteria in consortium in sediments was observed following exposure to Ag-NPs. In general microbial communities may be resistant in estuarine systems to the antimicrobial effects of commercial Ag-NPs, but key microorganisms, such as Pelobacter propionicus, disappeared following exposure to Ag-NPs. In conclusion, the T-RFLP analysis indicated that Ag-NPs have the potential to shape estuarine sediment bacterial community structure.

Electronic and optical properties of pristine and boron-nitrogen doped graphyne nanotubes.

First principle calculations with generalized gradient approximation were carried out to analyse the electronic and optical properties of armchair and zigzag graphyne nanotubes (GNTs). The possible application of these NTs in optoelectronic devices was also investigated. The GNTs were doped with boron (B) and nitrogen (N) atoms and the resulting band gap tuning was studied with respect to the B/N substitution site and increasing diameter of the NTs. The basis of this variation was examined using the partial density of states and crystal orbital Hamilton population analysis. A decreasing trend in the optical response was seen with an increase in the diameter of the NTs. The reported systems showed anisotropic behaviour in the low-energy region. The origin of the optical responses was monitored from the infrared to the UV region depending on the doping site of the B/N. As a result of the large band gap, low reflectivity and low refractive index, B/N GNTs have been established as a suitable system for novel optoelectronic devices. The strong absorption peaks in the UV region mean that they are a good choice for use in UV light protection.

Vitamin D receptor expression levels determine the severity and complexity of disease progression among leprosy reaction patients.

We studied the roles of vitamin D and its receptor, VDR, in the progression of leprosy. The majority of individuals with leprosy from Kolkata, India, with a type 1 or type 2 reaction have low levels of vitamin D3 in serum samples. Interestingly, individuals with a type 2 reaction associated with neuritis/erythema nodosum leprosum had very low VDR mRNA expression levels, ranging from 5% to 10%, compared to that of healthy control subjects; these patients also had a high bacilli index, ranging from 3+ to 5+. This is the first report to indicate that VDR expression levels may determine the complexity and severity of the progression of leprosy.

An electrochemical genosensor for Salmonella typhi on gold nanoparticles-mercaptosilane modified screen printed electrode.

In this work, we fabricated a system of integrated self-assembled layer of organosilane 3-mercaptopropyltrimethoxy silane (MPTS) on the screen printed electrode (SPE) and electrochemically deposited gold nanoparticle for Salmonella typhi detection employing Vi gene as a molecular marker. Thiolated DNA probe was immobilized on a gold nanoparticle (AuNP) modified SPE for DNA hybridization assay using methylene blue as redox (electroactive) hybridization indicator, and signal was monitored by differential pulse voltammetry (DPV) method. The modified SPE was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and atomic force microscopy (AFM) method. The DNA biosensor showed excellent performances with high sensitivity and good selectivity. The current response was linear with the target sequence concentrations ranging from 1.0 × 10(-11) to 0.5 × 10(-8)M and the detection limit was found to be 50 (± 2.1)pM. The DNA biosensor showed good discrimination ability to the one-base, two-base and three-base mismatched sequences. The fabricated genosensor could also be regenerated easily and reused for three to four times for further hybridization studies.

Increased drug resistance is associated with reduced glucose levels and an enhanced glycolysis phenotype.

BACKGROUND AND PURPOSE: The testing of anticancer compounds in vitro is usually performed in hyperglycaemic cell cultures, although many tumours and their in vivo microenvironments are hypoglycaemic. Here, we have assessed, in cultures of tumour cells, the effects of reduced glucose levels on resistance to anticancer drugs and investigated the underlying cellular mechanisms. EXPERIMENTAL APPROACH: PIK3CA mutant (AGS, HGC27), and wild-type (MKN45, NUGC4) gastric cancer cells were cultured in high-glucose (HG, 25 mM) or low-glucose (LG, 5 mM) media and tested for sensitivity to two cytotoxic compounds, 5-fluorouracil (5-FU) and carboplatin, the PI3K/mTOR inhibitor, PI103 and the mTOR inhibitor, Ku-0063794. KEY RESULTS: All cells had increased resistance to 5-FU and carboplatin when cultured in LG compared with HG conditions despite having similar growth and cell cycle characteristics. On treatment with PI103 or Ku-0063794, only the PIK3CA mutant cells displayed increased resistance in LG conditions. The PIK3CA mutant LG cells had selectively increased p-mTOR, p-S6, p-4EBP1, GLUT1 and lactate production, and reduced reactive oxygen species, consistent with increased glycolysis. Combination analysis indicated PI103 and Ku-0063794 were synergistic in PIK3CA mutant LG cells only. Synergism was accompanied by reduced mTOR signalling and increased autophagy. CONCLUSIONS AND IMPLICATIONS: Hypoglycaemia increased resistance to cytotoxic agents, especially in tumour cells with a high dependence on glycolysis. Dual inhibition of the PI3K/mTOR pathway may be able to attenuate such hypoglycaemia-associated resistance.

A deterministic thermostat for controlling temperature using all degrees of freedom.

We propose a new thermostat that uses all the phase space variables for controlling temperature and thus differs from the existing thermostats that control either the kinetic (e.g., Nose Hoover) or the configurational (e.g., Braga Travis) degrees of freedom. Our thermostat is a special case of the set of equations proposed by Kusnezov et al. [Ann. Phys. 204, 155 (1990)] and is derived using the extended system method. We show that it generates a canonical phase-space distribution. The performance of the thermostat is compared with those of Nose-Hoover kinetic thermostat and Braga-Travis configurational thermostat for a system (i) in thermal equilibrium, (ii) subjected to sudden temperature changes, and (iii) in steady state non-equilibrium under thermal conduction. We observe that all three thermostats perform similarly for systems in equilibrium. However, our thermostat performs the best in the thermal conduction problem by generating a consistent temperature profile across the conduction length. We expect this thermostat to be useful in other non-equilibrium scenarios as well.

Arsenic speciation in polychaetes (Annelida) and sediments from the intertidal mudflat of Sundarban mangrove wetland, India.

This paper documents the concentration of total arsenic and individual arsenic species in four soft-bottom benthic polychaetes (Perenereis cultifera, Ganganereis sootai, Lumbrinereis notocirrata and Dendronereis arborifera) along with host sediments from Sundarban mangrove wetland, India. An additional six sites were considered exclusively for surface sediments for this purpose. Polychaetes were collected along with the host sediments and measured for their total arsenic content using inductively coupled plasma mass spectrometry. Arsenic concentrations in polychaete body tissues varied greatly, suggesting species-specific characteristics and inherent peculiarities in arsenic metabolism. Arsenic was generally present in polychaetes as arsenate (As(V) ranges from 0.16 to 0.50 mg kg(-1)) or arsenite (As(III) ranges from 0.10 to 0.41 mg kg(-1)) (30-53 % as inorganic As) and dimethylarsinic acid (DMA(V) <1-25 %). Arsenobetaine (AB < 16 %), and PO(4)-arsenoriboside (8-48 %) were also detected as minor constituents, whilst monomethylarsonic acid (MA(V)) was not detected in any of the polychaetes. The highest total As (14.7 mg kg(-1) dry wt) was observed in the polychaete D. arborifera collected from the vicinity of a sewage outfall in which the majority of As was present as an uncharacterised compound (10.3 mg kg(-1) dry wt) eluted prior to AB. Host sediments ranged from 2.5 to 10.4 mg kg(-1) of total As. This work supports the importance of speciation analysis of As, because of the ubiquitous occurrence of this metalloid in the environment, and its variable toxicity depending on chemical form. It is also the first work to report the composition of As species in polychaetes from the Indian Sundarban wetlands.

Novel biopolymer gel electrolyte for dye-sensitized solar cell application.

We report a new biopolymer electrolyte for dye sensitized solar cell application. To develop polymer electrolyte, potassium iodide have been added in agarose biopolymer matrix and characterized using various techniques like complex impedance spectroscopy, Infrared spectroscopy (IR), X-ray diffraction (XRD), scanning electron microscopy (SEM). Complex impedance spectroscopy shows many folds enhancement in ionic conductivity (σ) by salt doping and conductivity maxima was obtained near 60:40 composition. Infrared spectroscopy confirms the formation of composite nature. XRD revels the reduction of crystallinity by salt doping as well affirms the composite nature. Scanning electron microscopy (SEM) shows reduction in crystallinity of gel matrix by salt doping which is a known favorable condition for ionic conductivity enhancement. To further affirm the conductivity enhancement in the gel electrolyte system a theoretical hopping model is also described in details. A DSSC has been developed using maximum electrical conductivity film which shows 0.54% efficiency at 1 sun condition.

Efficiency of health care system in India: an inter-state analysis using DEA approach.

Since independence a massive personnel and public health infrastructure has been created in India. However, there is no competition and hardly any choice to the poor patients resulting in poor quality services leading to allocative and technical inefficiencies. This study uses the data envelopment analysis model to assess and compare the efficiency of health system within various states of India. It shows the inadequacy of health infrastructure and manpower in the inefficient states where poor people are concentrated. Among the determinants of efficiency female literacy, poverty level, institutional delivery, and full immunization of children are proved to be important factors in explaining efficiency of health system in India.

Development of an eco-friendly method to convert life expired composite propellant into liquid fertilizer.

Large quantity of composite propellants is produced as waste due to life expiry of missiles/rejection of propellant lots during manufacturing. The environmental protection agency does not allow the hazardous materials for open burning/open detonation. Therefore, a systematic study has been carried out to develop a method for the disposal of composite propellant into liquid fertilizer without affecting the environment. In this study, propellant compositions were digested in dilute nitric acid followed by neutralization with 5M KOH solution to get precipitated out aluminium as aluminium hydroxide and finally the obtained liquid was treated with orthophosphoric acid for further neutralization. The liquid fertilizer, thus, obtained was characterized for nitrate and phosphate content using ion chromatography while ICP-AES was used for the estimation of potassium, aluminium and other noxious metallic elements such as Pb, Cd, As, Cr, Cu, Ni and Zn. The analyses data indicate that liquid fertilizer is free from aluminium and noxious metallic elements while ratio of nitrogen, phosphorous and potassium are close to the Indian NPK value.

Multiple signal transduction pathways alterations during nerve agent toxicity.

Nerve agent toxicity is primarily due to the synaptic build up of toxic levels of acetylcholine. The acute lethal effects of the nerve agents are generally attributed to respiratory failure caused by a combination of effects at both central and peripheral levels and are further complicated by copious secretions, muscle fasciculations, and convulsions. In addition to this, a range of non cholinergic effects have been observed. The development of effective treatment to block multiple effects resulting from nerve agent exposure is hampered by a limited understanding of the molecular changes responsible for their persistent effects. Excessive accumulation of acetylcholine leads to activation nicotinic and muscarinic acetylcholine receptors, these receptors activate diverse kind of cellular responses by distinct signaling pathways. Metabolism of cyclic nucleotides, membrane phospholipids, activation of a multitude of protein kinases and the induction of transcription factors are the key biochemical steps and pathways that have been investigated. This review will focus on the effects of nerve agents on signal transduction pathways; particularly, MAP kinases, protein kinase C isozymes, calcium calmodulin dependent protein kinase II (CaMKII) and on cytoskeletal proteins, calpain, and certain transcription factors and discusses how such changes may be involved in nerve agent induced neurotoxicity. Alterations in these key brain proteins could explain the neurological impairments following nerve agent exposure. A better understanding of the whole picture may lead to new pharmacological interventions aimed to improve or modulate those signal transduction pathways affected during nerve agent poisoning or associated pathologies that are responsible for neuronal disturbances.

Gene expression and phosphoprotein profile of certain key neuronal signaling proteins following soman intoxication.

Nerve agents irreversibly inhibit acetylcholinesterase (AChE), leading to cholinergic crisis and death at acute exposure levels. The complexity, delayed onset, and persistent nature of nerve agent induced CNS effects need to be elucidated to block their multiple effects. In the present study gene expression and phosphoprotein profile of certain key neuronal proteins were studied after soman exposure. Quantitative real time PCR analysis of c-Fos, Bax, CREB and caspase 3 genes in the hippocampus, cortex and cerebellum showed that only c-Fos and Bax mRNA expression was increased significantly. Western blot analysis also confirmed the induction of c-Fos at early time points both at 0.5 and 1.0 LD(50) dose of soman exposure. Acute soman exposure caused perturbations in the phosphorylation status of ERK, JNK, p38 MAPK, CREB, c-Jun and NF-κB in all the three brain regions. The primary target for soman toxicity, AChE was inhibited in blood and brain up to 90%. Therapeutic treatment comprising of HI-6, atropine and diazepam has completely protected animals from death and reactivated soman inhibited AChE up to 40% in the plasma and RBC. This therapeutic regime also reduced soman induced Bax expression to near control levels, but could not reverse the soman induced changes in c-Fos expression and phosphorylation levels completely. Results suggest that exposure to soman caused persistent changes in these key brain proteins, which could lead to the development of complex neurotoxic effects and there is an urgent need for development of better drugs to stop multiple effects of nerve agents poisoning.

Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules and their antitubercular properties.

New series of quinoline-oxazolidinone hybrid molecules were synthesized based on the preliminary docking studies. All the newly synthesized compounds were characterized by spectral analyses. The newly synthesized compounds were screened for their antimycobacterial properties based on the promising preliminary antibacterial screening results. Amongst tested compounds, compounds 8a, 8j and 13a were active at 0.65 µg/mL against Mycobacterium tuberculosis H(37)Rv strain. The mode of action of these active compounds was carried out by docking of receptor enoyl-ACP reductase with newly synthesized candidate ligands 8a, 8j and 13a. These compounds exhibited well established bonds with one or more amino acids in the receptor active pocket. From the docking studies, compound 8j was considered to be the best inhibitor.

Attenuation of sulfur mustard toxicity by S-2(2-aminoethylamino)ethyl phenyl sulfide (DRDE-07) in mouse liver.

Sulfur mustard (SM) (bis-(2-chloroethyl) sulfide) is a chemical warfare agent. Evaluation of toxicity and protective effect of DRDE-07 (S-2(2-aminoethylamino)ethyl phenyl sulfide) was studied in mouse liver after SM challenging. Female mice were given orally 0.2 LD(50) of DRDE-07 (249 mg/kg body weight) and exposed percutaneously with 1.0 LD(50) of SM (8.1 mg/kg body weight). Gene expression profiles were determined using global genome microarray analysis at 3 days post-exposure. DRDE-07 alone treated animal showed significant upregulation to metabolism of xenobiotics by cytochrome P450 pathways. Genes related to cell adhesion molecules (CAMs), were downregulated. DRDE-07 pretreated SM exposed animals showed upregulation of xenobiotic cytochrome P450 pathway genes. Antigen presenting, cell adhesion molecules, cytokine, cytokine receptor metabolism, fatty acid metabolism, glutathione metabolism, cell cycle signaling pathway genes showed downregulation. The present study showed that SM-induced toxicity in mouse liver was attenuated by the pretreatment with DRDE-07.

Changes of protein oxidation, calpain and cytoskeletal proteins (alpha tubulin and pNF-H) levels in rat brain after nerve agent poisoning.

Highly toxic organophosphorus (OP) nerve agents, sarin and soman act by inhibiting acetylcholinesterase (AChE) function at neuronal synapses and cause many toxic effects including death within minutes. The effect of nerve agents on protein oxidation, calpain, and cytoskeletal protein levels was not well known. In the present study we investigated these parameters after subcutaneous injection of sarin (120 µg/kg) and soman (80 µg/kg) in the rat brain. Results indicate that several rat brain proteins were intensely oxidized after nerve agent poisoning. Immunoreactivity levels of µ-calpain were significantly elevated in cerebral cortex and cerebellum regions of rat brain from 2.5 h to 30 days. Alpha tubulin levels reduced from 1 to 7 days in the supernatant and 1 to 3 days in the pellet fractions of cerebellum and cerebral cortex, where as phosphorylation of high molecular weight neurofilament (pNF-H) was increased significantly in nerve agent intoxicated rat brains as compared to control rats. AChE activity was inhibited up to 3 days after nerve agent exposure in plasma and brain. Results suggest that altered protein oxidation, calpain and cytoskeletal protein levels are due to multiple mechanisms of nerve agents actions and these changes might be involved in nerve agent induced complex neurotoxicity.

Detection of mycoplasma contamination in cell substrates using reverse transcription-PCR assays.

AIMS: To assess the limit of detection (LOD) and the feasibility of 16S rRNA-based reverse transcription-PCR (RT-PCR) assays for advanced detection of mycoplasma contamination in cell substrates. MATERIALS AND METHODS: The RT-PCR approach is based on detecting the 16S rRNA molecules that, in contrast to genomic bacterial DNA, are represented by multiple copies in mycoplasma cell. The number of 16S rRNA molecules in mycoplasma cells of five species i.e. Mycoplasma arginini, Myc. fermentans, Myc. hyorhinis, Myc. orale and Acholeplasma laidlawii, all known to be frequent cell line contaminants in industrial and research laboratories, was measured using molecular methods. The results of two independently prepared mycoplasma cultures harvested at the stationary phase of their growth showed that the 16S rRNA copy number per cell varied in the range from about 400 to 2000 copies, depending on species, but stayed close between different preparations of one species. The assessment of the LOD of the in-house 16S rRNA-based RT-PCR was performed using samples of MDCK cell culture spiked with different amounts of five aforementioned mycoplasma species. To minimize the bias in methods comparison, the LOD of the RT-PCR assay was expressed in terms of genome equivalents (GEs) and compared with that determined for highly optimized 16S rDNA-based mycoplasma testing methods previously described in scientific literature. CONCLUSIONS: The results of the study showed that the in-house 16S rRNA-based RT-PCR assay was able to reliably detect the presence of less than one mycoplasma GE that is at least 10-fold higher of the LOD previously determined for well-optimized 16S rDNA-based assays developed and described by other researchers. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the study showed that rapid RT-PCR methods based on the detection of bacterial 16S rRNA are able to expedite mycoplasma testing of cell cultures (1-2 days vs 28 days) and to ensure the limits of detection comparable to that of currently used culture-based mycoplasma testing methods.