Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study

Purpose: To study the capacity of an internally cooled radiofrequency (RF) bipolar applicator to create sufficiently deep thermal lesions in hepatic tissue. Materials and methods: Three complementary methodologies were employed to check the electrical and thermal behaviour of the applicator under test. The experimental studies were based on excised bovine (ex vivo study) and porcine liver (in vivo study) and the theoretical models were solved by means of the finite element method (FEM). Results: Experimental and computational results showed good agreement in terms of impedance progress and lesion depth (4 and 4.5 mm respectively for ex vivo conditions, and approximately 7 and 9 mm respectively for in vivo conditions), although the lesion widths were overestimated by the computer simulations. This could have been due to the method used to assess the thermal lesions; the experimental lesions were assessed by the white coagulation zone, whereas the tissue damage function was used to assess the computational lesions. Conclusions: The experimental results suggest that this applicator could create in vivo lesions to a depth of around 7mm. It was also observed that the thermal lesion is mainly confined to the area between both electrodes, which would allow lesion width to be controlled by selecting a specific applicator design. The comparison between the experimental and computational results suggests that the theoretical model could be usefully applied in further studies of the performance of this device. © 2012 Informa UK Ltd All rights reserved.This work received financial support from the Spanish Plan Nacional de I+D+I del Ministerio de Ciencia e Innovacion TEC2011-27133-C02-(01 and 02), from Universitat Politecnica de Valencia (INNOVA11-01-5502; and PAID-06-11 Ref. 1988). A. Gonzalez-Suarez is the recipient of grant VaLi+D (ACIF/2011/194) from the Generalitat Valenciana. The proof-reading of this paper was funded by the Universitat Politecnica de Valencia, Spain. The authors alone are responsible for the content and writing of the paper.González Suárez, A.; Trujillo Guillen, M.; Burdío Pinilla, F.; Andaluz Martínez, AM.; Berjano Zanón, E. (2012). Feasibility study of an internally cooled bipolar applicator for RF coagulation of hepatic tissue: Experimental and computational study. International Journal of Hyperthermia. 28(7):663-673. https://doi.org/10.3109/02656736.2012.716900S663673287Topp, S. A., McClurken, M., Lipson, D., Upadhya, G. A., Ritter, J. H., Linehan, D., & Strasberg, S. M. (2004). Saline-Linked Surface Radiofrequency Ablation. Annals of Surgery, 239(4), 518-527. doi:10.1097/01.sla.0000118927.83650.a4Gnerlich, J. L., Ritter, J. H., Linehan, D. C., Hawkins, W. G., & Strasberg, S. M. (2009). Saline-Linked Surface Radiofrequency Ablation. Annals of Surgery, 250(1), 96-102. doi:10.1097/sla.0b013e3181ae91afSakamoto, Y., Yamamoto, J., Kokudo, N., Seki, M., Kosuge, T., Yamaguchi, T., … Makuuchi, M. (2004). Bloodless liver resection using the Monopolar Floating Ball plus Ligasure diathermy: Preliminary results of 16 liver resections. World Journal of Surgery, 28(2), 166-172. doi:10.1007/s00268-003-7167-5Poon, R. T., Fan, S. T., & Wong, J. (2005). Liver resection using a saline-linked radiofrequency dissecting sealer for transection of the liver. Journal of the American College of Surgeons, 200(2), 308-313. doi:10.1016/j.jamcollsurg.2004.10.008EVERETT IV, T. H., LEE, K. W., WILSON, E. E., GUERRA, J. M., VAROSY, P. D., & OLGIN, J. E. (2008). Safety Profiles and Lesion Size of Different Radiofrequency Ablation Technologies: A Comparison of Large Tip, Open and Closed Irrigation Catheters. Journal of Cardiovascular Electrophysiology, 20(3), 325-335. doi:10.1111/j.1540-8167.2008.01305.xYokoyama, K., Nakagawa, H., Wittkampf, F. H. M., Pitha, J. V., Lazzara, R., & Jackman, W. M. (2006). Comparison of Electrode Cooling Between Internal and Open Irrigation in Radiofrequency Ablation Lesion Depth and Incidence of Thrombus and Steam Pop. Circulation, 113(1), 11-19. doi:10.1161/circulationaha.105.540062Demazumder, D., Mirotznik, M. S., & Schwartzman, D. (2001). Journal of Interventional Cardiac Electrophysiology, 5(4), 391-400. doi:10.1023/a:1013241927388Cooper, J. M., Sapp, J. L., Tedrow, U., Pellegrini, C. P., Robinson, D., Epstein, L. M., & Stevenson, W. G. (2004). Ablation with an internally irrigated radiofrequency catheter: Learning how to avoid steam pops. Heart Rhythm, 1(3), 329-333. doi:10.1016/j.hrthm.2004.04.019Burdío, F., Grande, L., Berjano, E., Martinez-Serrano, M., Poves, I., Burdío, J. M., … Güemes, A. (2010). A new single-instrument technique for parenchyma division and hemostasis in liver resection: a clinical feasibility study. The American Journal of Surgery, 200(6), e75-e80. doi:10.1016/j.amjsurg.2010.02.020Ríos, J. S., Zalabardo, J. M. S., Burdio, F., Berjano, E., Moros, M., Gonzalez, A., … Güemes, A. (2011). Single Instrument for Hemostatic Control in Laparoscopic Partial Nephrectomy in a Porcine Model Without Renal Vascular Clamping. Journal of Endourology, 25(6), 1005-1011. doi:10.1089/end.2010.0557Dorcaratto, D., Burdío, F., Fondevila, D., Andaluz, A., Poves, I., Martinez, M. A., … Grande, L. (2012). Laparoscopic Distal Pancreatectomy: Feasibility Study of Radiofrequency-Assisted Transection in a Porcine Model. Journal of Laparoendoscopic & Advanced Surgical Techniques, 22(3), 242-248. doi:10.1089/lap.2011.0417Zeh, A., Messer, J., Davis, J., Vasarhelyi, A., & Wohlrab, D. (2010). The Aquamantys System—An Alternative To Reduce Blood Loss in Primary Total Hip Arthroplasty? The Journal of Arthroplasty, 25(7), 1072-1077. doi:10.1016/j.arth.2009.10.008Sprunger, J., & Herrell, S. D. (2005). Partial Laparoscopic Nephrectomy Using Monopolar Saline-Coupled Radiofrequency Device: Animal Model and Tissue Effect Characterization. Journal of Endourology, 19(4), 513-519. doi:10.1089/end.2005.19.513Voeller, R. K., Zierer, A., Lall, S. C., Sakamoto, S., Schuessler, R. B., & Damiano, R. J. (2010). Efficacy of a novel bipolar radiofrequency ablation device on the beating heart for atrial fibrillation ablation: A long-term porcine study. The Journal of Thoracic and Cardiovascular Surgery, 140(1), 203-208. doi:10.1016/j.jtcvs.2009.06.034Pai, M., Spalding, D., Jiao, L., & Habib, N. (2012). Use of Bipolar Radiofrequency in Parenchymal Transection of the Liver, Pancreas and Kidney. Digestive Surgery, 29(1), 43-47. doi:10.1159/000335732Berjano, E. J. (2006). BioMedical Engineering OnLine, 5(1), 24. doi:10.1186/1475-925x-5-24Tungjitkusolmun, S., Staelin, S. T., Haemmerich, D., Jang-Zern Tsai, Hong Cao, Webster, J. G., … Vorperian, V. R. (2002). Three-dimensional finite-element analyses for radio-frequency hepatic tumor ablation. IEEE Transactions on Biomedical Engineering, 49(1), 3-9. doi:10.1109/10.972834Doss, J. D. (1982). Calculation of electric fields in conductive media. Medical Physics, 9(4), 566-573. doi:10.1118/1.595107Abraham, J. P., & Sparrow, E. M. (2007). A thermal-ablation bioheat model including liquid-to-vapor phase change, pressure- and necrosis-dependent perfusion, and moisture-dependent properties. International Journal of Heat and Mass Transfer, 50(13-14), 2537-2544. doi:10.1016/j.ijheatmasstransfer.2006.11.045Jo, B., & Aksan, A. (2010). Prediction of the extent of thermal damage in the cornea during conductive keratoplasty. Journal of Thermal Biology, 35(4), 167-174. doi:10.1016/j.jtherbio.2010.02.004Pearce, J., Panescu, D., & Thomsen, S. (2005). Simulation of diopter changes in radio frequency conductive keratoplasty in the cornea. Modelling in Medicine and Biology VI. doi:10.2495/bio050451Yang, D., Converse, M. C., Mahvi, D. M., & Webster, J. G. (2007). Expanding the Bioheat Equation to Include Tissue Internal Water Evaporation During Heating. IEEE Transactions on Biomedical Engineering, 54(8), 1382-1388. doi:10.1109/tbme.2007.890740Zhao, G., Zhang, H.-F., Guo, X.-J., Luo, D.-W., & Gao, D.-Y. (2007). Effect of blood flow and metabolism on multidimensional heat transfer during cryosurgery. Medical Engineering & Physics, 29(2), 205-215. doi:10.1016/j.medengphy.2006.03.005Pätz T, Körger T, Preusser T, Simulation of radiofrequency ablation including water evaporation. In: IFMBE Proceedings of the World Congress on Medical Physics and Biomedical Engineering 25/IV, 2009, 1287–1290Berjano, E. J., Burdío, F., Navarro, A. C., Burdío, J. M., Güemes, A., Aldana, O., … Gregorio, M. A. de. (2006). Improved perfusion system for bipolar radiofrequency ablation of liver: preliminary findings from a computer modeling study. Physiological Measurement, 27(10), N55-N66. doi:10.1088/0967-3334/27/10/n03Burdío, F., Berjano, E. J., Navarro, A., Burdío, J. M., Grande, L., Gonzalez, A., … Lequerica, J. L. (2009). Research and development of a new RF-assisted device for bloodless rapid transection of the liver: Computational modeling and in vivo experiments. BioMedical Engineering OnLine, 8(1), 6. doi:10.1186/1475-925x-8-6Chang, I. A., & Nguyen, U. D. (2004). BioMedical Engineering OnLine, 3(1), 27. doi:10.1186/1475-925x-3-27Beop-Min Kim, Jacques, S. L., Rastegar, S., Thomsen, S., & Motamedi, M. (1996). Nonlinear finite-element analysis of the role of dynamic changes in blood perfusion and optical properties in laser coagulation of tissue. IEEE Journal of Selected Topics in Quantum Electronics, 2(4), 922-933. doi:10.1109/2944.577317Panescu, D., Whayne, J. G., Fleischman, S. D., Mirotznik, M. S., Swanson, D. K., & Webster, J. G. (1995). Three-dimensional finite element analysis of current density and temperature distributions during radio-frequency ablation. IEEE Transactions on Biomedical Engineering, 42(9), 879-890. doi:10.1109/10.412649González-Suárez A, Alba J, Trujillo M, Berjano E, Experimental and theoretical study of an internally cooled bipolar electrode for RF coagulation of biological tissues. Conf Proc IEEE Eng Med Biol Soc 2011;6878–6881Rosenberg, A. G. (2007). Reducing Blood Loss in Total Joint Surgery With a Saline-Coupled Bipolar Sealing Technology. The Journal of Arthroplasty, 22(4), 82-85. doi:10.1016/j.arth.2007.02.018PETERSEN, H. H., ROMAN-GONZALEZ, J., JOHNSON, S. B., HASTRUP SVENDSEN, J., HAUNSO, S., & PACKER, D. L. (2004). Mechanisms for Enlarging Lesion Size During Irrigated Tip Radiofrequency Ablation:. Is There a Virtual Electrode Effect? Journal of Interventional Cardiology, 17(3), 171-177. doi:10.1111/j.1540-8183.2004.09879.

Correlation of LNCR rasiRNAs Expression with Heterochromatin Formation during Development of the Holocentric Insect Spodoptera frugiperda

Repeat-associated small interfering RNAs (rasiRNAs) are derived from various genomic repetitive elements and ensure genomic stability by silencing endogenous transposable elements. Here we describe a novel subset of 46 rasiRNAs named LNCR rasiRNAs due to their homology with one long non-coding RNA (LNCR) of Spodoptera frugiperda. LNCR operates as the intermediate of an unclassified transposable element (TE-LNCR). TE-LNCR is a very invasive transposable element, present in high copy numbers in the S. frugiperda genome. LNCR rasiRNAs are single-stranded RNAs without a prominent nucleotide motif, which are organized in two distinct, strand-specific clusters. The expression of LNCR and LNCR rasiRNAs is developmentally regulated. Formation of heterochromatin in the genomic region where three copies of the TE-LNCR are embedded was followed by chromatin immunoprecipitation (ChIP) and we observed this chromatin undergo dynamic changes during development. In summary, increased LNCR expression in certain developmental stages is followed by the appearance of a variety of LNCR rasiRNAs which appears to correlate with subsequent accumulation of a heterochromatic histone mark and silencing of the genomic region with TE-LNCR. These results support the notion that a repeat-associated small interfering RNA pathway is linked to heterochromatin formation and/or maintenance during development to establish repression of the TE-LNCR transposable element. This study provides insights into the rasiRNA silencing pathway and its role in the formation of fluctuating heterochromatin during the development of one holocentric organism

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

Meditation or Medication? Mindfulness training versus medication in the treatment of childhood ADHD: a randomized controlled trial

Background Attention-Deficit-Hyperactivity-Disorder (ADHD) is, with a prevalence of 5 %, a highly common childhood disorder, and has severe impact on the lives of youngsters and their families. Medication is often the treatment of choice, as it currently is most effective. However, medication has only short-term effects, treatment adherence is often low and most importantly; medication has serious side effects. Therefore, there is a need for other interventions for youngsters with ADHD. Mindfulness training is emerging as a potentially effective training for children and adolescents with ADHD. The aim of this study is to compare the (cost) effectiveness of mindfulness training to the (cost) effectiveness of methylphenidate in children with ADHD on measures of attention and hyperactivity/impulsivity. Methods/design A multicenter randomized controlled trial with 2 follow-up measurements will be used to measure the effects of mindfulness training versus the effects of methylphenidate. Participants will be youngsters (aged 9 to 18) of both sexes diagnosed with ADHD, referred to urban and rural mental healthcare centers. We aim to include 120 families. The mindfulness training, using the MYmind protocol, will be conducted in small groups, and consists of 8 weekly 1.5-h sessions. Youngsters learn to focus and enhance their attention, awareness, and self-control by doing mindfulness exercises. Parents will follow a parallel mindful parenting training in which they learn to be fully present in the here and now with their child in a non-judgmental way, to take care of themselves, and to respond rather than react to difficult behavior of their child. Short-acting methylphenidate will be administered individually and monitored by a child psychiatrist. Assessments will take place at pre-test, post-test, and at follow-up 1 and 2 (respectively 4 and 10 months after the start of treatment). Informants are parents, children, teachers, and researchers. Discussion This study will inform mental health care professionals and health insurance companies about the clinical and cost effectiveness of mindfulness training for children and adolescents with ADHD and their parents compared to the effectiveness of methylphenidate. Limitations and several types of bias that are anticipated for this study are discussed