Reproductive Risk Factors for Breast Cancer: A Case Control Study

Background: Breast cancer is second most important cancer among Indian women. Although risk factors are not much prevalent as in western countries, incidence rate is increasing in India. The study was undertaken to study various risk factors associated with breast cancer. Methods: A hospital based group matched case control study was undertaken to identify risk factors. The study consisted of 105 hospitalized cases confirmed on histopathology and 210 group matched controls selected from urban field practice area, Sadar, without any malignancy. Bivariate analyses included odds ratio (OR), 95% confidence interval (CI) for odds ratio. Results: Earlier age at menarche ≤ 12 years of age, late age at first full term delivery, nulliparity, Lack of breast-feeding were found to be significantly associated with the risk of breast cancer in both pre menopausal & post menopausal women while age at menopause at or after 50 years was significantly associated with the risk in post menopausal women. Conclusions: Study suggests that the changes in menstrual and reproductive patterns among women i.e. early age at menarche and late age at first childbirth and some environmental factors in Central India may have contributed to the increase in breast cancer risk, particularly among younger women

Metastatic appendiceal adenocarcinoma presenting late as epididymo-orchitis: a case report and review of literature

BACKGROUND: Whereas testicular metastases are in themselves a rare entity, testicular secondaries from an appendiceal carcinoma have not yet been described. The case also illustrates the diagnostic dilemma of a tumour presenting as epididymo-orchitis. CASE PRESENTATION: The authors present a case of an appendiceal carcinoma that, two years after radical therapy, manifested as a secondary in the testis. It was misdiagnosed as an epididymo-orchitis and was only revealed through histology. CONCLUSIONS: Practitioners need to remember that long-standing testicular inflammation may result form secondary tumours. Even "exotic" primary tumours in the medical history of the patient must give rise to an increased suspicion threshold

Generation of subnanometric platinum with high stability during transformation of a 2D zeolite into 3D

[EN] Single metal atoms and metal clusters have attracted much attention thanks to their advantageous capabilities as heterogeneous catalysts. However, the generation of stable single atoms and clusters on a solid support is still challenging. Herein, we report a new strategy for the generation of single Pt atoms and Pt clusters with exceptionally high thermal stability, formed within purely siliceous MCM-22 during the growth of a two-dimensional zeolite into three dimensions. These subnanometric Pt species are stabilized by MCM-22, even after treatment in air up to 540 degrees C. Furthermore, these stable Pt species confined within internal framework cavities show size-selective catalysis for the hydrogenation of alkenes. High-temperature oxidation-reduction treatments result in the growth of encapsulated Pt species to small nanoparticles in the approximate size range of 1 to 2 nm. The stability and catalytic activity of encapsulated Pt species is also reflected in the dehydrogenation of propane to propylene.This work was funded by the Spanish Government (Consolider Ingenio 2010-MULTICAT (CSD2009-00050) and MAT2014-52085-C2-1-P) and by the Generalitat Valenciana (Prometeo). The Severo Ochoa Program (SEV-2012-0267) is gratefully acknowledged. L.L. thanks ITQ for a contract. The authors also thank the Microscopy Service of UPV for the TEM and STEM measurements. The HAADF-HRSTEM works were conducted in the Laboratorio de Microscopias Avanzadas (LMA) at the Instituto de Nanociencia de Aragon (INA)-Universidad de Zaragoza (Spain), a Spanish ICTS National Facility. Some of the research leading to these results has received funding from the European Union Seventh Framework Program under Grant Agreement 312483-ESTEEM2 (Integrated Infrastructure Initiative-I3). R.A. also acknowledges funding from the Spanish Ministerio de Economia y Competitividad (FIS2013-46159-C3-3-P) and the European Union Horizon 2020 research and innovation programme under the Marie Sldodowska-Curie grant agreement No. 642742.Liu, L.; Díaz Morales, UM.; Arenal, R.; Agostini, G.; Concepción Heydorn, P.; Corma Canós, A. (2017). Generation of subnanometric platinum with high stability during transformation of a 2D zeolite into 3D. Nature Materials. 16(1):132-138. https://doi.org/10.1038/NMAT4757S132138161Boronat, M., Leyva-Perez, A. & Corma, A. Theoretical and experimental insights into the origin of the catalytic activity of subnanometric gold clusters: attempts to predict reactivity with clusters and nanoparticles of gold. Acc. Chem. Res. 47, 834–844 (2014).Flytzani-Stephanopoulos, M. & Gates, B. C. Atomically dispersed supported metal catalysts. Ann. Rev. Chem. Bio. Eng. 3, 545–574 (2012).Gates, B. C. Supported metal clusters: synthesis, structure, and catalysis. Chem. Rev. 95, 511–522 (1995).Corma, A. et al. Exceptional oxidation activity with size-controlled supported gold clusters of low atomicity. Nat. Chem. 5, 775–781 (2013).Yang, M. et al. Catalytically active Au-O(OH)x-species stabilized by alkali ions on zeolites and mesoporous oxides. Science 346, 1498–1501 (2014).Rivallan, M. et al. Platinum sintering on H-ZSM-5 followed by chemometrics of CO adsorption and 2D pressure-jump IR spectroscopy of adsorbed species. Angew. Chem. Int. Ed. 49, 785–789 (2010).Zecevic, J., van der Eerden, A. M., Friedrich, H., de Jongh, P. E. & de Jong, K. P. Heterogeneities of the nanostructure of platinum/zeolite Y catalysts revealed by electron tomography. ACS Nano 7, 3698–3705 (2013).Philippaerts, A. et al. Unprecedented shape selectivity in hydrogenation of triacylglycerol molecules with Pt/ZSM-5 zeolite. Angew. Chem. Int. Ed. 50, 3947–3949 (2011).Kim, J., Kim, W., Seo, Y., Kim, J.-C. & Ryoo, R. n-Heptane hydroisomerization over Pt/MFI zeolite nanosheets: effects of zeolite crystal thickness and platinum location. J. Catalys. 301, 187–197 (2013).Goel, S., Wu, Z., Zones, S. I. & Iglesia, E. Synthesis and catalytic properties of metal clusters encapsulated within small-pore (SOD, GIS, ANA) zeolites. J. Am. Chem. Soc. 134, 17688–17695 (2012).Choi, M., Wu, Z. & Iglesia, E. Mercaptosilane-assisted synthesis of metal clusters within zeolites and catalytic consequences of encapsulation. J. Am. Chem. Soc. 132, 9129–9137 (2010).Choi, M., Yook, S. & Kim, H. Hydrogen spillover in encapsulated metal catalysts: new opportunities for designing advanced hydroprocessing catalysts. ChemCatChem 7, 1048–1057 (2015).Kulkarni, A., Lobo-Lapidus, R. J. & Gates, B. C. Metal clusters on supports: synthesis, structure, reactivity, and catalytic properties. Chem. Commun. 46, 5997–6015 (2010).Guzman, J. & Gates, B. C. Supported molecular catalysts: metal complexes and clusters on oxides and zeolites. Dalton Trans. 1, 3303–3318 (2003).Leonowicz, M. E., Lawton, J. A., Lawton, S. L. & Rubin, M. K. MCM-22: a molecular sieve with two independent multidimensional channel systems. Science 264, 1910–1913 (1994).Camblor, M. A. et al. A new microporous polymorph of silica isomorphous to zeolite MCM-22. Chem. Mater. 8, 2415–2417 (1996).Hyotanishi, M., Isomura, Y., Yamamoto, H., Kawasaki, H. & Obora, Y. Surfactant-free synthesis of palladium nanoclusters for their use in catalytic cross-coupling reactions. Chem. Commun. 47, 5750–5752 (2011).Duchesne, P. N. & Zhang, P. Local structure of fluorescent platinum nanoclusters. Nanoscale 4, 4199–4205 (2012).Lu, J., Aydin, C., Browning, N. D. & Gates, B. C. Imaging isolated gold atom catalytic sites in zeolite NaY. Angew. Chem. Int. Ed. 51, 5842–5846 (2012).Yacamán, M. J., Santiago, U. & Mejía-Rosales, S. in Advanced Transmission Electron Microscopy: Applications to Nanomaterials (eds Francis, L., Mayoral, A. & Arenal, R.) 1–29 (Springer, 2015).Jena, P., Khanna, S. N. & Rao, B. K. Physics and Chemistry of Finite Systems: From Clusters to Crystals (Springer, 1992).Yamasaki, J. et al. Ultramicroscopy 151, 224–231 (2015).Sohlberg, K., Pennycook, T. J., Zhoud, W. & Pennycook, S. J. Insights into the physical chemistry of materials from advances in HAADF-STEM. Phys. Chem. Chem. Phys. 17, 3982–4006 (2015).Aydin, C., Lu, J., Browning, N. D. & Gates, B. C. A ‘smart’ catalyst: sinter-resistant supported iridium clusters visualized with electron microscopy. Angew. Chem. Int. Ed. 51, 5929–5934 (2012).Wei, H. et al. FeOx-supported platinum single-atom and pseudo-single-atom catalysts for chemoselective hydrogenation of functionalized nitroarenes. Nat. Commun. 5, 5634 (2014).Addou, R. et al. Influence of hydroxyls on Pd atom mobility and clustering on rutile TiO2(011)-2 × 1. ACS Nano 8, 6321–6333 (2014).Jung, U. et al. Comparative in operando studies in heterogeneous catalysis: atomic and electronic structural features in the hydrogenation of ethylene over supported Pd and Pt catalysts. ACS Catal. 5, 1539–1551 (2015).Agostini, G. et al. Effect of different face centered cubic nanoparticle distributions on particle size and surface area determination: a theoretical study. J. Phys. Chem. C 118, 4085–4094 (2014).Alexeev, O. & Gates, B. C. EXAFS characterization of supported metal-complex and metal-cluster catalysts made from organometallic precursors. Top. Catal. 10, 273–293 (2000).Chakraborty, I., Bhuin, R. G., Bhat, S. & Pradeep, T. Blue emitting undecaplatinum clusters. Nanoscale 6, 8561–8564 (2014).Zheng, J., Nicovich, P. R. & Dickson, R. M. Highly fluorescent noble-metal quantum dots. Ann. Rev. Phys. Chem. 58, 409–431 (2007).Okrut, A. et al. Selective molecular recognition by nanoscale environments in a supported iridium cluster catalyst. Nat. Nanotech. 9, 459–465 (2014).Zhou, C. et al. On the sequential hydrogen dissociative chemisorption on small platinum clusters: a density functional theory study. J. Phys. Chem. C 111, 12773–12778 (2007).De La Cruz, C. & Sheppard, N. An exploration of the surfaces of some Pt/SiO2 catalysts using CO as an infrared spectroscopic probe. Spectrochim. Acta A 50, 271–285 (1994).Klünker, C., Balden, M., Lehwald, S. & Daum, W. CO stretching vibrations on Pt(111) and Pt(110) studied by sum frequency generation. Surf. Sci. 360, 104–111 (1996).Stakheev, A. Y., Shpiro, E. S., Jaeger, N. I. & Schulz-Ekloff, G. Electronic state and location of Pt metal clusters in KL zeolite: FTIR study of CO chemisorption. Catal. Lett. 32, 147–158 (1995).Heiz, U., Sanchez, A., Abbet, S. & Schneider, W. D. Catalytic oxidation of carbon monoxide on monodispersed platinum clusters: each atom counts. J. Am. Chem. Soc. 121, 3214–3217 (1999).Levitas, V. I. & Samani, K. Size and mechanics effects in surface-induced melting of nanoparticles. Nat. Commun. 2, 284 (2011).Jiang, H., Moon, K.-s., Dong, H., Hua, F. & Wong, C. P. Size-dependent melting properties of tin nanoparticles. Chem. Phys. Lett. 429, 492–496 (2006).Nanda, K. K., Kruis, F. E. & Fissan, H. Evaporation of free PbS nanoparticles: evidence of the Kelvin effect. Phys. Rev. Lett. 89, 256103 (2002).Vajda, S. et al. Subnanometre platinum clusters as highly active and selective catalysts for the oxidative dehydrogenation of propane. Nat. Mater. 8, 213–216 (2009).Ortalan, V., Uzun, A., Gates, B. C. & Browning, N. D. Direct imaging of single metal atoms and clusters in the pores of dealuminated HY zeolite. Nat. Nanotech. 5, 506–510 (2010).Koch, C. Determination of Core Structure Periodicity and Point Defect Density along Dislocations PhD thesis, Univ. Arizona (2002).Mathon, O. et al. The time-resolved and extreme conditions XAS (TEXAS) facility at the European Synchrotron Radiation Facility: the general-purpose EXAFS bending-magnet beamline BM23. J. Synchrotron Radiat. 22, 1548–1554 (2015).Newville, M. IFEFFIT: interactive XAFS analysis and FEFF fitting. J. Synchrotron Radiat. 8, 322–324 (2001)

Transforming Growth Factor β Signaling Pathway Associated Gene Polymorphisms May Explain Lower Breast Cancer Risk in Western Indian Women

Transforming growth factor β1 (TGFB1) T29C and TGF β receptor type 1 (TGFBR1) 6A/9A polymorphisms have been implicated in the modulation of risk for breast cancer in Caucasian women. We analyzed these polymorphisms and combinations of their genotypes, in pre menopausal breast cancer patients (N = 182) and healthy women (N = 236) from western India as well as in breast cancer patients and healthy women from the Parsi community (N = 48 & 171, respectively). Western Indian women were characterized by a higher frequency of TGFB1*C allele of the TGF β T29C polymorphism (0.48 vs 0.44) and a significantly lower frequency of TGFBR1*6A allele of the TGFBR1 6A/9A polymorphism (0.02 vs 0.068, p<0.01) as compared to healthy Parsi women. A strong protective effect of TGFB1*29C allele was seen in younger western Indian women (<40 yrs; OR = 0.45, 95% CI 0.25–0.81). Compared to healthy women, the strikingly higher frequencies of low or intermediate TGF β signalers in patients suggested a strong influence of the combination of these genotypes on the risk for breast cancer in Parsi women (for intermediate signalers, OR = 4.47 95%CI 1.01–19.69). The frequency of low signalers in Parsi healthy women, while comparable to that reported in Europeans and Americans, was three times higher than that in healthy women from western India (10.6% vs 3.3%, p<0.01). These observations, in conjunction with the low incidence rate of breast cancer in Indian women compared to White women, raise a possibility that the higher frequency of TGFB1*29C allele and lower frequency of TGFBR1*6A allele may represent important genetic determinants that together contribute to a lower risk of breast cancer in western Indian women

Disambiguating ventral striatum fMRI-related bold signal during reward prediction in schizophrenia

Reward detection, surprise detection and prediction-error signaling have all been proposed as roles for the ventral striatum (vStr). Previous neuroimaging studies of striatal function in schizophrenia have found attenuated neural responses to reward-related prediction errors; however, as prediction errors represent a discrepancy in mesolimbic neural activity between expected and actual events, it is critical to examine responses to both expected and unexpected rewards (URs) in conjunction with expected and UR omissions in order to clarify the nature of ventral striatal dysfunction in schizophrenia. In the present study, healthy adults and people with schizophrenia were tested with a reward-related prediction-error task during functional magnetic resonance imaging to determine whether schizophrenia is associated with altered neural responses in the vStr to rewards, surprise prediction errors or all three factors. In healthy adults, we found neural responses in the vStr were correlated more specifically with prediction errors than to surprising events or reward stimuli alone. People with schizophrenia did not display the normal differential activation between expected and URs, which was partially due to exaggerated ventral striatal responses to expected rewards (right vStr) but also included blunted responses to unexpected outcomes (left vStr). This finding shows that neural responses, which typically are elicited by surprise, can also occur to well-predicted events in schizophrenia and identifies aberrant activity in the vStr as a key node of dysfunction in the neural circuitry used to differentiate expected and unexpected feedback in schizophrenia

Phenotypic Screen of Early-Developing Larvae of the Blood Fluke, Schistosoma mansoni, using RNA Interference

RNA interference (RNAi) represents the only method currently available for manipulating gene-specific expression in Schistosoma spp., although application of this technology as a functional genomic profiling tool has yet to be explored. In the present study 32 genes, including antioxidants, transcription factors, cell signaling molecules and metabolic enzymes, were selected to determine if gene knockdown by RNAi was associated with morphologically definable phenotypic changes in early intramolluscan larval development. Transcript selection was based on their high expression in in vitro cultured S. mansoni primary sporocysts and/or their potential involvement in developmental processes. Miracidia were allowed to transform to sporocysts in the presence of synthesized double-stranded RNAs (dsRNAs) and cultivated for 7 days, during which time developing larvae were closely observed for phenotypic changes including failure/delay in transformation, loss of motility, altered growth and death. Of the phenotypes evaluated, only one was consistently detected; namely a reduction in sporocyst size based on length measurements. The size-reducing phenotype was observed in 11 of the 33 (33%) dsRNA treatment groups, and of these 11 phenotype-associated genes (superoxide dismutase, Smad1, RHO2, Smad2, Cav2A, ring box, GST26, calcineurin B, Smad4, lactate dehydrogenase and EF1α), only 6 demonstrated a significant and consistent knockdown of specific transcript expression. Unexpectedly one phenotype-linked gene, superoxide dismutase (SOD), was highly induced (∼1600-fold) upon dsRNA exposure. Variation in dsRNA-mediated silencing effects also was evident in the group of sporocysts that lacked any definable phenotype. Out of 22 nonphenotype-expressing dsRNA treatments (myosin, PKCB, HEXBP, calcium channel, Sma2, RHO1, PKC receptor, DHHC, PepcK, calreticulin, calpain, Smeg, 14.3.3, K5, SPO1, SmZF1, fibrillarin, GST28, GPx, TPx1, TPx2 and TPx2/TPx1), 12 were assessed for the transcript levels. Of those, 6 genes exhibited consistent reductions in steady-state transcript levels, while expression level for the rest remained unchanged. Results demonstrate that the efficacy of dsRNA-treatment in producing consistent phenotypic changes and/or altered gene expression levels in S. mansoni sporocysts is highly dependent on the selected gene (or the specific dsRNA sequence used) and the timing of evaluation after treatment. Although RNAi holds great promise as a functional genomics tool for larval schistosomes, our finding of potential off-target or nonspecific effects of some dsRNA treatments and variable efficiencies in specific gene knockdown indicate a critical need for gene-specific testing and optimization as an essential part of experimental design, execution and data interpretation

Whole Genomes of Chandipura Virus Isolates and Comparative Analysis with Other Rhabdoviruses

The Chandipura virus (CHPV) belonging to the Vesiculovirus genus and Rhabdoviridae family, has recently been associated with a number of encephalitis epidemics, with high mortality in children, in different parts of India. No full length genome sequences of CHPV isolates were available in GenBank and little is known about the molecular markers for pathogenesis. In the present study, we provide the complete genomic sequences of four isolates from epidemics during 2003–2007. These sequences along with the deduced sequence of the prototype isolate of 1965 were analysed using phylogeny, motif search, homology modeling and epitope prediction methods. Comparison with other rhaboviruses was also done for functional extrapolations. All CHPV isolates clustered with the Isfahan virus and maintained several functional motifs of other rhabdoviruses. A notable difference with the prototype vesiculovirus, Vesicular Stomatitis Virus was in the L-domain flanking sequences of the M protein that are known to be crucial for interaction with host proteins. With respect to the prototype isolate, significant additional mutations were acquired in the 2003–2007 isolates. Several mutations in G mapped onto probable antigenic sites. A mutation in N mapped onto regions crucial for N-N interaction and a putative T-cell epitope. A mutation in the Casein kinase II phosphorylation site in P may attribute to increased rates of phosphorylation. Gene junction comparison revealed changes in the M-G junction of all the epidemic isolates that may have implications on read-through and gene transcription levels. The study can form the basis for further experimental verification and provide additional insights into the virulence determinants of the CHPV

HLA-C and HIV-1: friends or foes?

The major histocompatibility complex class I protein HLA-C plays a crucial role as a molecule capable of sending inhibitory signals to both natural killer (NK) cells and cytotoxic T lymphocytes (CTL) via binding to killer cell Ig-like receptors (KIR). Recently HLA-C has been recognized as a key molecule in the immune control of HIV-1. Expression of HLA-C is modulated by a microRNA binding site. HLA-C alleles that bear substitutions in the microRNA binding site are more expressed at the cell surface and associated with the control of HIV-1 viral load, suggesting a role of HLA-C in the presentation of antigenic peptides to CTLs. This review highlights the role of HLA-C in association with HIV-1 viral load, but also addresses the contradiction of the association between high cell surface expression of an inhibitory molecule and strong cell-mediated immunity. To explore additional mechanisms of control of HIV-1 replication by HLA-C, we address specific features of the molecule, like its tendency to be expressed as open conformer upon cell activation, which endows it with a unique capacity to associate with other cell surface molecules as well as with HIV-1 proteins

State-Space Analysis of Time-Varying Higher-Order Spike Correlation for Multiple Neural Spike Train Data

Precise spike coordination between the spiking activities of multiple neurons is suggested as an indication of coordinated network activity in active cell assemblies. Spike correlation analysis aims to identify such cooperative network activity by detecting excess spike synchrony in simultaneously recorded multiple neural spike sequences. Cooperative activity is expected to organize dynamically during behavior and cognition; therefore currently available analysis techniques must be extended to enable the estimation of multiple time-varying spike interactions between neurons simultaneously. In particular, new methods must take advantage of the simultaneous observations of multiple neurons by addressing their higher-order dependencies, which cannot be revealed by pairwise analyses alone. In this paper, we develop a method for estimating time-varying spike interactions by means of a state-space analysis. Discretized parallel spike sequences are modeled as multi-variate binary processes using a log-linear model that provides a well-defined measure of higher-order spike correlation in an information geometry framework. We construct a recursive Bayesian filter/smoother for the extraction of spike interaction parameters. This method can simultaneously estimate the dynamic pairwise spike interactions of multiple single neurons, thereby extending the Ising/spin-glass model analysis of multiple neural spike train data to a nonstationary analysis. Furthermore, the method can estimate dynamic higher-order spike interactions. To validate the inclusion of the higher-order terms in the model, we construct an approximation method to assess the goodness-of-fit to spike data. In addition, we formulate a test method for the presence of higher-order spike correlation even in nonstationary spike data, e.g., data from awake behaving animals. The utility of the proposed methods is tested using simulated spike data with known underlying correlation dynamics. Finally, we apply the methods to neural spike data simultaneously recorded from the motor cortex of an awake monkey and demonstrate that the higher-order spike correlation organizes dynamically in relation to a behavioral demand