Choosing treatment for localised prostate cancer: A patient-conducted-interview study

Objectives: Treatment choice can be particularly difficult in localised prostate cancer because of the uncertainty involved. Indeed, some men prefer maintaining their masculine identity and quality of life to potentially securing longer-term survival through surgery or radiotherapy. UK health services are now obliged to leave the choice of treatment to the patient and the aim of this study is to improve understanding of patients’ experiences of choosing treatment. Methods: A one-day participative workshop where men of six months post-diagnosis design and conduct audio and video interviews on each other about their experiences of choosing treatment. Results: The findings show that treatment choice is a complex process combining emotional and rational elements. Information gathering and delegation to professional expertise were two key themes that emerged. Conclusions: The findings emphasise that treatment choice for localised prostate cancer is little like the traditional notions of consumerism from which it is derived. Importantly, the results illustrate, from a patient perspective, how health professionals can engage in their roles as information providers and as experts

A SCN9A gene-encoded dorsal root ganglia sodium channel polymorphism associated with severe fibromyalgia

<p>Abstract</p> <p>Background</p> <p>A consistent line of investigation suggests that autonomic nervous system dysfunction may explain the multi-system features of fibromyalgia (FM); and that FM is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia (DRG) are key sympathetic-nociceptive short-circuit sites. Sodium channels located in DRG (particularly Nav1.7) act as molecular gatekeepers for pain detection. Nav1.7 is encoded in gene SCN9A of chromosome 2q24.3 and is predominantly expressed in the DRG pain-sensing neurons and sympathetic ganglia neurons. Several SCN9A sodium channelopathies have been recognized as the cause of rare painful dysautonomic syndromes such as paroxysmal extreme pain disorder and primary erythromelalgia. The aim of this study was to search for an association between fibromyalgia and several SCN9A sodium channels gene polymorphisms.</p> <p>Methods</p> <p>We studied 73 Mexican women suffering from FM and 48 age-matched women who considered themselves healthy. All participants filled out the Fibromyalgia Impact Questionnaire (FIQ). Genomic DNA from whole blood containing EDTA was extracted by standard techniques. The following SCN9A single-nucleotide polymorphisms (SNP) were determined by 5' exonuclease TaqMan assays: rs4371369; rs4387806; rs4453709; rs4597545; rs6746030; rs6754031; rs7607967; rs12620053; rs12994338; and rs13017637.</p> <p>Results</p> <p>The frequency of the rs6754031 polymorphism was significantly different in both groups (<it>P </it>= 0.036) mostly due to an absence of the GG genotype in controls. Interestingly; patients with this rs6754031 GG genotype had higher FIQ scores (median = 80; percentile 25/75 = 69/88) than patients with the GT genotype (median = 63; percentile 25/75 = 58/73; <it>P </it>= 0.002) and the TT genotype (median = 71; percentile 25/75 = 64/77; <it>P </it>= 0.001).</p> <p>Conclusion</p> <p>In this ethnic group; a disabling form of FM is associated to a particular SCN9A sodium channel gene variant. These preliminary results raise the possibility that some patients with severe FM may have a dorsal root ganglia sodium channelopathy.</p

Radiosensitive melanoma cell line with mutation of the gene for ataxia telangiectasia.

The human melanoma cell lines MM96L, A2058 and HT144 were examined for sensitivity to ionizing radiation and UVB radiation. HT144 demonstrated a significant increase in sensitivity to ionizing and UVB radiation compared with the MM96L and A2058 cells. Sensitivity to both agents was associated with susceptibility to apoptosis. Using a protein truncation assay, a mutation for the gene for ataxia telangiectasia (ATM) was identified in HT144 cells. This was confirmed to be a homozygous mutation by subsequent sequencing of the abnormal region. Protein truncation assay of the other two cell lines showed no abnormality. The results suggest that somatic mutation of the A-T gene may be important in determining tumour radiosensitivity

X-ray nanoimaging of Nd3+ optically active ions embedded in Sr0.5Ba0.5Nb2O6 nanocrystals

[EN] The spatial distribution of Sr0.5Ba0.5Nb2O6 nanocrystals is analyzed in a borate-based glass-ceramic by a synchrotron hard X-ray nanoimaging tool. Based on X-ray excited optical luminescence, we examined 2D projections of the Nd3+ optically active ions in the Sr0.5Ba0.5Nb2O6 nanocrystals, as well as in the glassy phase where they are embedded. Our findings reveal areas of agglomerations and/or clusters of nanocrystals ascribed to the diffusion coefficients of their constituent elements. They are characterized by high Nd3+ concentrations that may act as heterogeneous agents for the nucleation and growth of these nanocrystals. (C) 2017 Optical Society of AmericaMINECO, EU-FEDER and CSIC through the projects MAT2013-46649-C4-4-P, MAT201571070-REDC, MAT2016-75586-C4-2-P, MAT2016-75586-C4-4-P, 201550I021 and 201660I001, respectively. JAS acknowledges the Spanish Program Ramón y Cajal for his fellowship. We also thank the ESRF for the beam time allocated and experimental facilities.Martínez-Criado, G.; Alén, B.; Sans-Tresserras, JÁ.; Lozano-Gorrín, A.; Haro-González, P.; Martin, I.; Lavin, V. (2017). X-ray nanoimaging of Nd3+ optically active ions embedded in Sr0.5Ba0.5Nb2O6 nanocrystals. Optical Materials Express. 7(7):2424-2431. https://doi.org/10.1364/OME.7.002424S2424243177Nagata, K., Yamamoto, Y., Igarashi, H., & Okazaki, K. (1981). Properties of the hot-pressed strontium barium niobate ceramics. Ferroelectrics, 38(1), 853-856. doi:10.1080/00150198108209556Imai, T., Yagi, S., Yamazaki, H., & Ono, M. (1999). Effects of Heat Treatment on Photorefractive Sensitivity of Ce- and Eu-Doped Strontium Barium Niobate. Japanese Journal of Applied Physics, 38(Part 1, No. 4A), 1984-1988. doi:10.1143/jjap.38.1984Volk, T., Isakov, D., Salobutin, V., Ivleva, L., Lykov, P., Ramzaev, V., & Wöhlecke, M. (2004). Effects of Ni doping on properties of strontium–barium–niobate crystals. Solid State Communications, 130(3-4), 223-226. doi:10.1016/j.ssc.2004.01.039Romero, J. J., Andreeta, M. R. B., Andreeta, E. R. M., Bausá, L. E., Hernandes, A. C., & García Solé, J. (2004). Growth and characterization of Nd-doped SBN single crystal fibers. Applied Physics A, 78(7), 1037-1042. doi:10.1007/s00339-003-2151-3Chayapiwut, N., Honma, T., Benino, Y., Fujiwara, T., & Komatsu, T. (2005). Synthesis of Sm3+-doped strontium barium niobate crystals in glass by samarium atom heat processing. Journal of Solid State Chemistry, 178(11), 3507-3513. doi:10.1016/j.jssc.2005.09.002Haro-González, P., Martín, I. R., Martín, L. L., León-Luis, S. F., Pérez-Rodríguez, C., & Lavín, V. (2011). Characterization of Er3+ and Nd3+ doped Strontium Barium Niobate glass ceramic as temperature sensors. Optical Materials, 33(5), 742-745. doi:10.1016/j.optmat.2010.11.026Ivleva, L. I., Volk, T. R., Isakov, D. V., Gladkii, V. V., Polozkov, N. M., & Lykov, P. A. (2002). Growth and ferroelectric properties of Nd-doped strontium–barium niobate crystals. Journal of Crystal Growth, 237-239, 700-702. doi:10.1016/s0022-0248(01)01997-2Marcinkevičius, A., Juodkazis, S., Watanabe, M., Miwa, M., Matsuo, S., Misawa, H., & Nishii, J. (2001). Femtosecond laser-assisted three-dimensional microfabrication in silica. Optics Letters, 26(5), 277. doi:10.1364/ol.26.000277Sato, R., Benino, Y., Fujiwara, T., & Komatsu, T. (2001). YAG laser-induced crystalline dot patterning in samarium tellurite glasses. Journal of Non-Crystalline Solids, 289(1-3), 228-232. doi:10.1016/s0022-3093(01)00736-0Haro-González, P., Martín, L. L., González-Pérez, S., & Martín, I. R. (2010). Formation of Nd3+ doped Strontium Barium Niobate nanocrystals by two different methods. Optical Materials, 32(10), 1389-1392. doi:10.1016/j.optmat.2010.03.011Haro-González, P., Martín, I. R., & Creus, A. H. (2010). Nanocrystals distribution inside the writing lines in a glass matrix using Argon laser irradiation. Optics Express, 18(2), 582. doi:10.1364/oe.18.000582Haro-González, P., Martín, I. R., Arbelo-Jorge, E., González-Pérez, S., Cáceres, J. M., & Núñez, P. (2008). Laser irradiation in Nd3+ doped strontium barium niobate glass. Journal of Applied Physics, 104(1), 013112. doi:10.1063/1.2952011Kowalska, D., Haro-González, P., Martín, I. R., & Cáceres, J. M. (2010). Analysis of the optical properties of Er3+-doped strontium barium niobate nanocrystals using time-resolved laser spectroscopy. Applied Physics A, 99(4), 771-776. doi:10.1007/s00339-010-5716-yPellicer-Porres, J., Segura, A., Martínez-Criado, G., Rodríguez-Mendoza, U. R., & Lavín, V. (2012). Formation of nanostructures in Eu3+doped glass–ceramics: an XAS study. Journal of Physics: Condensed Matter, 25(2), 025303. doi:10.1088/0953-8984/25/2/025303Martínez-Criado, G., Alén, B., Sans, J. A., Homs, A., Kieffer, I., Tucoulou, R., … Yi, G. (2012). Spatially resolved X-ray excited optical luminescence. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 284, 36-39. doi:10.1016/j.nimb.2011.08.013Martínez-Criado, G., Sans, J. A., Segura-Ruiz, J., Tucoulou, R., Solé, A. V., Homs, A., … Alén, B. (2011). X-ray excited optical luminescence imaging of InGaN nano-LEDs. physica status solidi (c), 9(3-4), 628-630. doi:10.1002/pssc.201100430Villanova, J., Segura-Ruiz, J., Lafford, T., & Martinez-Criado, G. (2012). Synchrotron microanalysis techniques applied to potential photovoltaic materials. Journal of Synchrotron Radiation, 19(4), 521-524. doi:10.1107/s0909049512021383Smith, J., Akbari-Sharbaf, A., Ward, M. J., Murphy, M. W., Fanchini, G., & Kong Sham, T. (2013). Luminescence properties of defects in nanocrystalline ZnO. Journal of Applied Physics, 113(9), 093104. doi:10.1063/1.4794001Armelao, L., Heigl, F., Jürgensen, A., Blyth, R. I. R., Regier, T., Zhou, X.-T., & Sham, T. K. (2007). X-ray Excited Optical Luminescence Studies of ZnO and Eu-Doped ZnO Nanostructures. The Journal of Physical Chemistry C, 111(28), 10194-10200. doi:10.1021/jp071379fMartínez-Criado, G., Villanova, J., Tucoulou, R., Salomon, D., Suuronen, J.-P., Labouré, S., … Morse, J. (2016). ID16B: a hard X-ray nanoprobe beamline at the ESRF for nano-analysis. Journal of Synchrotron Radiation, 23(1), 344-352. doi:10.1107/s1600577515019839Jamieson, P. B., Abrahams, S. C., & Bernstein, J. L. (1968). Ferroelectric Tungsten Bronze‐Type Crystal Structures. I. Barium Strontium Niobate Ba0.27Sr0.75Nb2O5.78. The Journal of Chemical Physics, 48(11), 5048-5057. doi:10.1063/1.1668176Haro-González, P., Martín, I. R., & Hernández Creus, A. (2011). Nanocrystals formation on Ho3+ doped strontium barium niobate glass. Journal of Luminescence, 131(4), 657-661. doi:10.1016/j.jlumin.2010.11.011Lavı́n, V., Rodrı́guez-Mendoza, U. R., Martı́n, I. R., & Rodrı́guez, V. D. (2003). Optical spectroscopy analysis of the Eu3+ ions local structure in calcium diborate glasses. Journal of Non-Crystalline Solids, 319(1-2), 200-216. doi:10.1016/s0022-3093(02)01914-2Chernaya, T. S., Volk, T. R., Verin, I. A., Ivleva, L. I., & Simonov, V. I. (2002). Atomic structure of (Sr0.50Ba0.50)Nb2O6 single crystals in the series of (SrxBa1 − x )Nb2O6 compounds. Crystallography Reports, 47(2), 213-216. doi:10.1134/1.1466494Erbil, A., Cargill III, G. S., Frahm, R., & Boehme, R. F. (1988). Total-electron-yield current measurements for near-surface extended x-ray-absorption fine structure. Physical Review B, 37(5), 2450-2464. doi:10.1103/physrevb.37.2450Solé, V. A., Papillon, E., Cotte, M., Walter, P., & Susini, J. (2007). A multiplatform code for the analysis of energy-dispersive X-ray fluorescence spectra. Spectrochimica Acta Part B: Atomic Spectroscopy, 62(1), 63-68. doi:10.1016/j.sab.2006.12.002Martínez-Criado, G., Homs, A., Alén, B., Sans, J. A., Segura-Ruiz, J., Molina-Sánchez, A., … Yi, G.-C. (2012). Probing Quantum Confinement within Single Core–Multishell Nanowires. Nano Letters, 12(11), 5829-5834. doi:10.1021/nl303178uMartínez-Criado, G., Segura-Ruiz, J., Alén, B., Eymery, J., Rogalev, A., Tucoulou, R., & Homs, A. (2014). Exploring Single Semiconductor Nanowires with a Multimodal Hard X-ray Nanoprobe. Advanced Materials, 26(46), 7873-7879. doi:10.1002/adma.201304345Shyu, J.-J., & Wang, J.-R. (2000). Crystallization and Dielectric Properties of SrO-BaO-Nb2O5-SiO2Tungsten-Bronze Glass-Ceramics. Journal of the American Ceramic Society, 83(12), 3135-3140. doi:10.1111/j.1151-2916.2000.tb01694.

Interleukin-1 beta-converting enzyme-like protease cleaves DNA-dependent protein kinase in cytotoxic T cell killing.

Cytotoxic T cells (CTL) represent the major defense mechanism against the spread of virus infection. It is believed that the pore-forming protein, perforin, facilitates the entry of a series of serine proteases (particularly granzyme B) into the target cell which ultimately leads to DNA fragmentation and apoptosis. We demonstrate here that during CTL-mediated cytolysis the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), an enzyme implicated in the repair of double strand breaks in DNA, is specifically cleaved by an interleukin (IL)-1 beta-converting enzyme (ICE)-like protease. A serine protease inhibitor, 3,4-dichloroisocoumarin (DCl), which is known to block granzyme B activity, inhibited CTL-induced apoptosis and prevented the degradation of DNA-PKcs in cells but failed to prevent the degradation of purified DNA-PKcs by CTL extracts. However, Tyr-Val-Ala-Asp-CH2Cl (YVAD-CMK) and other cysteine protease inhibitors prevented the degradation of purified DNA-PKcs by CTL extracts. Furthermore, incubation of DNA-PKcs with granzyme B did not produce the same cleavage pattern observed in cells undergoing apoptosis and when this substrate was incubated with either CTL extracts or the ICE-like protease, CPP32. Sequence analysis revealed that the cleavage site in DNA-PKcs during CTL killing was the same as that when this substrate was exposed to CPP32. This study demonstrates for the first time that the cleavage of DNA-PKcs in this intact cell system is exclusively due to an ICE-like protease

Costs of Biopsy and Complications in Patients with Lung Cancer

PURPOSE: To describe the distribution of diagnostic procedures, rates of complications, and total cost of biopsies for patients with lung cancer. PATIENTS AND METHODS: Observational study using data from IBM Marketscan(®) Databases for continuously insured adult patients with a primary lung cancer diagnosis and treatment between July 2013 and June 2017. Costs of lung cancer diagnosis covered 6 months prior to index biopsy through treatment. Costs of chest CT scans, biopsy, and post-procedural complications were estimated from total payments. Costs of biopsies incidental to inpatient admissions were estimated by comparable outpatient biopsies. RESULTS: The database included 22,870 patients who had a total of 37,160 biopsies, of which 16,009 (43.1%) were percutaneous, 14,997 (40.4%) bronchoscopic, 4072 (11.0%) surgical and 2082 (5.6%) mediastinoscopic. Multiple biopsies were performed on 41.9% of patients. The most common complications among patients receiving only one type of biopsy were pneumothorax (1304 patients, 8.4%), bleeding (744 patients, 4.8%) and intubation (400 patients, 2.6%). However, most complications did not require interventions that would add to costs. Median total costs were highest for inpatient surgical biopsies ($29,988) and lowest for outpatient percutaneous biopsies ($1028). Repeat biopsies of the same type increased costs by 40-80%. Complications account for 13% of total costs. CONCLUSION: Costs of biopsies to confirm lung cancer diagnosis vary substantially by type of biopsy and setting. Multiple biopsies, inpatient procedures and complications result in higher costs

The diversity of bioactive proteins in Australian snake venoms

Australian elapid snakes are among the most venomous in the world. Their venoms contain multiple components that target blood hemostasis, neuromuscular signaling, and the cardiovascular system. We describe here a comprehensive approach to separation and identification of the venom proteins from 18 of these snake species, representing nine genera. The venom protein components were separated by two-dimensional PAGE and identified using mass spectrometry and de novo peptide sequencing. The venoms are complex mixtures showing up to 200 protein spots varying in size from 10. These include many proteins identified previously in Australian snake venoms, homologs identified in other snake species, and some novel proteins. In many cases multiple trains of spots were typically observed in the higher molecular mass range (> 20 kDa) (indicative of post-translational modification). Venom proteins and their post-translational modifications were characterized using specific kantibodies, phosphoprotein- and glycoprotein-specific stains, enzymatic digestion, lectin binding, and antivenom reactivity. In the lower molecular weight range, several proteins were identified, but the predominant species were phospholipase A(2) and alpha-neurotoxins, both represented by different sequence variants. The higher molecular weight range contained proteases, nucleotidases, oxidases, and homologs of mammalian coagulation factors. This information together with the identification of several novel proteins (metalloproteinases, vespryns, phospholipase A(2) inhibitors, protein-disulfide isomerase, 5'-nucleotidases, cysteinerich secreted proteins, C-type lectins, and acetylcholinesterases) aids in understanding the lethal mechanisms of elapid snake venoms and represents a valuable resource for future development of novel human therapeutics

INTERGROWTH-21st v. local South African growth standards (Theron-Thompson) for identification of small-for-gestational-age fetuses in stillbirths : a closer look at variation across pregnancy

CITATION: Lavin, T., et al. 2019. INTERGROWTH-21st v. local South African growth standards (Theron-Thompson) for identification of small-for-gestational-age fetuses in stillbirths : a closer look at variation across pregnancy. South African Medical Journal, 109(7):519-525, doi:10.7196/SAMJ.2019.v109i7.13485.The original publication is available at http://www.samj.org.zaBackground. Global growth standards for fetuses were recently developed (INTERGROWTH-21st). It has been advocated that professional bodies should adopt these global standards. Objectives. To compare the ability of INTERGROWTH-21st with local standards (Theron-Thompson) to identify small-for-gestational-age (SGA) fetuses in stillbirths in the South African (SA) setting. Methods. Stillbirths across SA were investigated (>500 g, 28 - 40 weeks) between October 2013 and December 2016 (N=14 776). The study applied the INTERGROWTH-21st standards to classify stillbirths as <10th centile (SGA) compared with Theron-Thompson growth charts, across pregnancy overall and at specific gestational ages. Results. The prevalence of SGA was estimated at 32.2% and 31.1% by INTERGROWTH-21st and Theron-Thompson, respectively. INTERGROWTH-21st captured 13.8% more stillbirths as SGA in the earlier gestations (28 - 30 weeks, p<0.001), but 4.0% (n=315) fewer between 33 and 38 weeks (p<0.001). Observed agreement and the Kappa coefficient were lower at earlier gestations and at 34 - 36 weeks. Conclusions. Our findings demonstrated differences in the proportion of stillbirths considered SGA at each gestational age between the INTERGROWTH-21st and the local SA standard, which have not been considered previously by other studies.http://www.samj.org.za/index.php/samj/article/view/12640Publisher's versio