Computational Modeling of Open-Irrigated Electrodes for Radiofrequency Cardiac Ablation Including Blood Motion-Saline Flow Interaction

[EN] Radiofrequency catheter ablation (RFCA) is a routine treatment for cardiac arrhythmias. During RFCA, the electrode-tissue interface temperature should be kept below 80°C to avoid thrombus formation. Open-irrigated electrodes facilitate power delivery while keeping low temperatures around the catheter. No computational model of an open-irrigated electrode in endocardial RFCA accounting for both the saline irrigation flow and the blood motion in the cardiac chamber has been proposed yet. We present the first computational model including both effects at once. The model has been validated against existing experimental results. Computational results showed that the surface lesion width and blood temperature are affected by both the electrode design and the irrigation flow rate. Smaller surface lesion widths and blood temperatures are obtained with higher irrigation flow rate, while the lesion depth is not affected by changing the irrigation flow rate. Larger lesions are obtained with increasing power and the electrode-tissue contact. Also, larger lesions are obtained when electrode is placed horizontally. Overall, the computational findings are in close agreement with previous experimental results providing an excellent tool for future catheter research.This work was supported in part by the Basque Government through the BERC 2014-2017 program and by Spanish Ministry of Economy and Competitiveness MINECO through the BCAM Severo Ochoa excellence accreditation SEV-2013-0323, and also by the Spanish "Plan Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad" under Grant TEC2014-52383-C3-R (TEC2014-52383-C3-1-R) and Grant MTM201569992-R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This work was supported in part by the Basque Government through the BERC 2014-2017 program and by Spanish Ministry of Economy and Competitiveness MINECO through the BCAM Severo Ochoa excellence accreditation SEV-2013-0323, and also by the Spanish "Plan Estatal de Investigacion, Desarrollo e Innovacion Orientada a los Retos de la Sociedad" under Grant TEC2014-52383-C3-R (TEC2014-52383-C3-1-R) and Grant MTM2015-69992-RGonzález-Suárez, A.; Berjano, E.; Guerra, JM.; Gerardo-Giorda, L. (2016). Computational Modeling of Open-Irrigated Electrodes for Radiofrequency Cardiac Ablation Including Blood Motion-Saline Flow Interaction. PLoS ONE. 11(3):1-18. https://doi.org/10.1371/journal.pone.0150356118113DEMOLIN, J. M., EICK, O. J., MUNCH, K., KOULLICK, E., NAKAGAWA, H., & WITTKAMPF, F. H. M. (2002). Soft Thrombus Formation in Radiofrequency Catheter Ablation. Pacing and Clinical Electrophysiology, 25(8), 1219-1222. doi:10.1046/j.1460-9592.2002.01219.xMATSUDAIRA, K., NAKAGAWA, H., WITTKAMPF, F. H. M., YAMANASHI, W. S., IMAI, S., PITHA, J. V., … JACKMAN, W. M. (2003). High Incidence of Thrombus Formation Without Impedance Rise During Radiofrequency Ablation Using Electrode Temperature Control. Pacing and Clinical Electrophysiology, 26(5), 1227-1237. doi:10.1046/j.1460-9592.2003.t01-1-00173.xWOOD, M. A., GOLDBERG, S. M., PARVEZ, B., PATHAK, V., HOLLAND, K., ELLENBOGEN, A. L., … GOEL, A. (2009). Effect of Electrode Orientation on Lesion Sizes Produced by Irrigated Radiofrequency Ablation Catheters. Journal of Cardiovascular Electrophysiology, 20(11), 1262-1268. doi:10.1111/j.1540-8167.2009.01538.xEVERETT 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.xDemazumder, D., Mirotznik, M. S., & Schwartzman, D. (2001). Journal of Interventional Cardiac Electrophysiology, 5(4), 377-389. doi:10.1023/a:1013224110550Yokoyama, 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.105.540062Yokoyama, K., Nakagawa, H., Shah, D. C., Lambert, H., Leo, G., Aeby, N., … Jackman, W. M. (2008). Novel Contact Force Sensor Incorporated in Irrigated Radiofrequency Ablation Catheter Predicts Lesion Size and Incidence of Steam Pop and Thrombus. Circulation: Arrhythmia and Electrophysiology, 1(5), 354-362. doi:10.1161/circep.108.803650Nakagawa H. Comparison of 12 and 56 hole electrodes for open irrigated radiofrequency ablation in a canine thigh muscle preparation: improvement in thrombus reduction with 56 small irrigation holes. Biosense Webster 2010.WEISS, C., ANTZ, M., EICK, O., ESHAGZAIY, K., MEINERTZ, T., & WILLEMS, S. (2002). Radiofrequency Catheter Ablation Using Cooled Electrodes: Impact of Irrigation Flow Rate and Catheter Contact Pressure on Lesion Dimensions. Pacing and Clinical Electrophysiology, 25(4), 463-469. doi:10.1046/j.1460-9592.2002.00463.xPÉREZ, J. J., D’AVILA, A., ARYANA, A., & BERJANO, E. (2015). Electrical and Thermal Effects of Esophageal Temperature Probes on Radiofrequency Catheter Ablation of Atrial Fibrillation: Results from a Computational Modeling Study. Journal of Cardiovascular Electrophysiology, 26(5), 556-564. doi:10.1111/jce.12630Jain, M. K., & Wolf, P. D. (2000). A Three-Dimensional Finite Element Model of Radiofrequency Ablation with Blood Flow and its Experimental Validation. Annals of Biomedical Engineering, 28(9), 1075-1084. doi:10.1114/1.1310219Gopalakrishnan, J. (2002). A Mathematical Model for Irrigated Epicardial Radiofrequency Ablation. Annals of Biomedical Engineering, 30(7), 884-893. doi:10.1114/1.1507845Schutt, D., Berjano, E. J., & Haemmerich, D. (2009). Effect of electrode thermal conductivity in cardiac radiofrequency catheter ablation: A computational modeling study. International Journal of Hyperthermia, 25(2), 99-107. doi:10.1080/02656730802563051JAIN, M. K., TOMASSONI, G., RILEY, R. E., & WOLF, P. D. (1998). Effect of Skin Electrode Location on Radiofrequency Ablation Lesions: An In Vivo and a Three-Dimensional Finite Element Study. Journal of Cardiovascular Electrophysiology, 9(12), 1325-1335. doi:10.1111/j.1540-8167.1998.tb00108.xTungjitkusolmun, S., Woo, E. J., Cao, H., Tsai, J. Z., Vorperian, V. R., & Webster, J. G. (2000). Thermal—electrical finite element modelling for radio frequency cardiac ablation: Effects of changes in myocardial properties. Medical & Biological Engineering & Computing, 38(5), 562-568. doi:10.1007/bf02345754Abraham, 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.2006.11.045HAINES, D. E., & WATSON, D. D. (1989). Tissue Heating During Radiofrequency Catheter Ablation: A Thermodynamic Model and Observations in Isolated Perfused and Superfused Canine Right Ventricular Free Wall. Pacing and Clinical Electrophysiology, 12(6), 962-976. doi:10.1111/j.1540-8159.1989.tb05034.xDoss, J. D. (1982). Calculation of electric fields in conductive media. Medical Physics, 9(4), 566-573. doi:10.1118/1.595107Berjano, E. J. (2006). Theoretical modeling for radiofrequency ablation: state-of-the-art and challenges for the future. BioMedical Engineering OnLine, 5(1). doi:10.1186/1475-925x-5-24Nakagawa, H., Wittkampf, F. H. M., Yamanashi, W. S., Pitha, J. V., Imai, S., Campbell, B., … Jackman, W. M. (1998). Inverse Relationship Between Electrode Size and Lesion Size During Radiofrequency Ablation With Active Electrode Cooling. Circulation, 98(5), 458-465. doi:10.1161/01.cir.98.5.458Haemmerich, D., Chachati, L., Wright, A. S., Mahvi, D. M., Lee, F. T., & Webster, J. G. (2003). Hepatic radiofrequency ablation with internally cooled probes: effect of coolant temperature on lesion size. IEEE Transactions on Biomedical Engineering, 50(4), 493-500. doi:10.1109/tbme.2003.809488Jain, M. K., & Wolf, P. D. (1999). Temperature-controlled and constant-power radio-frequency ablation: what affects lesion growth? IEEE Transactions on Biomedical Engineering, 46(12), 1405-1412. doi:10.1109/10.804568NGUYEN, D. T., OLSON, M., ZHENG, L., BARHAM, W., MOSS, J. D., & SAUER, W. H. (2015). Effect of Irrigant Characteristics on Lesion Formation After Radiofrequency Energy Delivery Using Ablation Catheters with Actively Cooled Tips. Journal of Cardiovascular Electrophysiology, 26(7), 792-798. doi:10.1111/jce.12682Hong Cao, Vorperian, V. R., Tungjitkusolmun, S., Jan-Zern Tsai, Haemmerich, D., Young Bin Choy, & Webster, J. G. (2001). Flow effect on lesion formation in RF cardiac catheter ablation. IEEE Transactions on Biomedical Engineering, 48(4), 425-433. doi:10.1109/10.91570

Photo-Fenton oxidation of cylindrospermopsin at neutral pH with LEDs

Cylindrospermopsin (CYN) is a potent cyanobacterial toxin found in freshwaters worldwide. In this work, the feasibility of the photo-Fenton process under neutral pH using light emitting diodes as irradiation source for the removal of this hazardous cyanotoxin from freshwater was investigated. The impact of the kind of iron chelating agent (ethylenediamine-N, N′-disuccinic acid vs. ethylenedinitrilotetraacetic acid) as well as the effect of the main operating conditions viz. H2O2 dose, Fe(III) load, initial CYN concentration, and Fe(III):EDDS molar ratio on the performance of the process was systematically evaluated. EDDS was selected as the most appropriate iron chelating agent considering the kinetics of the process and the environmental impact (Vibrio fischeri and Artemia salina). Under optimized conditions ([H2O2] = 30 mg L−1; [Fe(III)] = 5 mg L−1; Fe(III):ligand = 1:0.5 (molar ratio)), complete removal of CYN was achieved in 15-min reaction time. Furthermore, the catalytic system showed to be effective in real water matrices (river and reservoir waters) spiked with CYN. Although the presence of inorganic ions (mainly HCO3−/CO32−) and dissolved organic carbon decreased the oxidation rate of CYN due to scavenging reactions and iron coordination, respectively, complete elimination of the cyanotoxin was achieved in all cases. The fate of EDDS along the process was also evaluated to demonstrate that the catalytic system investigated, apart from its effectiveness, warrants the complete absence of residues after reaction. Therefore, the proposed system constitutes a promising method for cyanotoxin treatment either as a drinking water treatment step in conventional plants or as a potential remediation strategy in the natural environmentOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research has been supported by the CYTED Ibero-American Science and Technology Program for Development (CYTED-2019) through the project TALGENTOX (PCI2020-112013) and by the Spanish Ministry for Science and Innovation (MICINN) through the project PID2019-105079RB-I00. D. Ortiz has received a FPU predoctoral grant (FPU19/04816) from the Spanish Ministry of Universities. M. Munoz has received a Ramón y Cajal postdoctoral contract (RYC-2016–20648) from the Spanish MINEC

Diabetes primary prevention program: new insights from data analysis of recruitment period

Primary Prevention of Diabetes Program in Buenos Aires Province evaluates the effectiveness of adopting healthy lifestyle to prevent type 2 diabetes (T2D) in people at high risk of developing it. We aimed to present preliminary data analysis of FINDRISC and laboratory measurements taken during recruitment of people for the Primary Prevention of Diabetes Program in Buenos Aires Province in the cities of La Plata, Berisso, and Ensenada, Argentina.Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Elgart, Jorge Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Bourgeois, Marcelo Javier. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro Interdisc.universitario Para la Salud; ArgentinaFil: Etchegoyen, Graciela Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Fantuzzi, Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Ré, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Ricart, Juan P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: García, Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Giampieri, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Gonzalez, Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Suárez Crivaro, Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Kronsbein, Peter. Niederrhein University of Applied Sciences Mönchengladbach; AlemaniaFil: Angelini, Julieta M.. Universidad Nacional de La Plata; ArgentinaFil: Martinez, Camilo. Universidad Nacional de La Plata; ArgentinaFil: Martinez, Jorge. Universidad Nacional de La Plata; ArgentinaFil: Ricart, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentin

Trajectories of Symptom Dimensions in Short-Term Response to Antipsychotic Treatment in Patients with a First Episode of Non-Affective Psychosis

Background Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data. Method This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables. Results Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension. Conclusions Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension

GJ357: A low-mass planetary system uncovered by precision radial-velocities and dynamical simulations

We report the detection of a new planetary system orbiting the nearby M2.5V star GJ357, using precision radial-velocities from three separate echelle spectrographs, HARPS, HiRES, and UVES. Three small planets have been confirmed in the system, with periods of 9.125+/-0.001, 3.9306+/-0.0003, and 55.70+/-0.05 days, and minimum masses of 3.33+/-0.48, 2.09+/-0.32, and 6.72+/-0.94 Me, respectively. The second planet in our system, GJ357c, was recently shown to transit by the Transiting Exoplanet Survey Satellite (TESS; Luque et al. 2019), but we could find no transit signatures for the other two planets. Dynamical analysis reveals the system is likely to be close to coplanar, is stable on Myrs timescales, and places strong upper limits on the masses of the two non-transiting planets b and d of 4.25 and 11.20 Me, respectively. Therefore, we confirm the system contains at least two super-Earths, and either a third super-Earth or mini-Neptune planet. GJ357b & c are found to be close to a 7:3 mean motion resonance, however no libration of the orbital parameters was found in our simulations. Analysis of the photometric lightcurve of the star from the TESS, when combined with our radial-velocities, reveal GJ357c has an absolute mass, radius, and density of 2.248+0.117-0.120 Me, 1.167+0.037-0.036 Re, and 7.757+0.889-0.789 g/cm3, respectively. Comparison to super-Earth structure models reveals the planet is likely an iron dominated world. The GJ357 system adds to the small sample of low-mass planetary systems with well constrained masses, and further observational and dynamical follow-up is warranted to better understand the overall population of small multi-planet systems in the solar neighbourhood.Comment: Manuscript accepted to MNRAS 15/10/201

The CHROMEVALOA Database: A Resource for the Evaluation of Okadaic Acid Contamination in the Marine Environment Based on the Chromatin-Associated Transcriptome of the Mussel Mytilus galloprovincialis

Okadaic Acid (OA) constitutes the main active principle in Diarrhetic Shellfish Poisoning (DSP) toxins produced during Harmful Algal Blooms (HABs), representing a serious threat for human consumers of edible shellfish. Furthermore, OA conveys critical deleterious effects for marine organisms due to its genotoxic potential. Many efforts have been dedicated to OA biomonitoring during the last three decades. However, it is only now with the current availability of detailed molecular information on DNA organization and the mechanisms involved in the maintenance of genome integrity, that a new arena starts opening up for the study of OA contamination. In the present work we address the links between OA genotoxicity and chromatin by combining Next Generation Sequencing (NGS) technologies and bioinformatics. To this end, we introduce CHROMEVALOAdb, a public database containing the chromatin-associated transcriptome of the mussel Mytilus galloprovincialis (a sentinel model organism) in response to OA exposure. This resource constitutes a leap forward for the development of chromatin-based biomarkers, paving the road towards the generation of powerful and sensitive tests for the detection and evaluation of the genotoxic effects of OA in coastal areas

Quantitative determination of c-myc facilitates the assessment of prognosis of OSCC patients

Myc genes are a family of proto-oncogenes whose proteins are implicated in the regulation of cell proliferation, differentiation and apoptosis, and in regulating the activity of genes involved in cell division. The aim of the present study was to establish a quantitative description of the expression of c-myc and evaluate its relationship with other clinical and prognostic factors, as well as to establish a multivariate survival prediction model. This is a retrospective study of 68 patients diagnosed with oral squamous cell carcinoma (OSCC). We constructed a tissue microarray for investigating the expression of c-myc by immunohistochemistry. Statistical analyses were carried out, and a multivariate model that predicts survival was established. The average expression of c-myc was 50.32 (SD, 26.05) with a range from 6.60 to 99.48; similar for initial and advanced tumor stages. Non-smoking patients had higher levels of c-myc, showing statistically significant differences (Kruskal-Wallis chi2=5.975; p=0.05). We found no statistically significant relationship between the quantitative expression of c-myc and any other clinical or pathological parameters. For each unit of increase of c-myc, the risk increased by 1.15 (p<0.001; HR, 1.150; 95% CI, 1062-1245). Further study of this protein, which may have a significant diagnostic, prognostic and therapeutic value is warranted. Its determination can be valuable when used together with other markers to assess the prognosis of OSCC patients

Electromagnetic assessment of UHF-RFID devices in healthcare environment

In this work, the evaluation of electromagnetic effect of Ultra High Frequency Radio Frequency Identification (UHF-RFID) passive tags used in the healthcare environment is presented. In order to evaluate exposure levels caused by EM field (865–868 MHz) of UHF-RFID readers, EM measurements in an anechoic chamber and in a real medical environment (Hospital Universitario de Canarias), as well as simulations by 3D Ray Launching algorithm, and of biophysical exposure effects in human models are presented. The results obtained show that the EM exposure is localized, in close vicinity of RFID reader and inversely proportional to its reading range. The EM exposure levels detected are sufficient to cause EM immunity effects in electronic devices (malfunctions in medical equipment or implants). Moreover, more than negligible direct effects in humans (exceeding relevant SAR values) were found only next to the reader, up to approximately 30% of the reading range. As a consequence, the EM risk could be firstly evaluated based on RFID parameters, but should include an in situ exposure assessment. It requires attention and additional studies, as increased applications of monitoring systems are observed in the healthcare sector—specifically when any system is located close to the workplace that is permanently occupied.This work was supported by Instituto de Salud Carlos III project “Electromagnetic Characterization in Smart Environments of Healthcare, and their involvement in Personal, Occupational, and Environmental Health” (PI14CIII/00056), and project (PI19CIII/00033) TMPY 508/19 “Metrics development for electromagnetic safety assessment in healthcare centers in the context of 5G“ from Sub-Directorate-General for Research Assessment and Promotion. The results of a research task (II.PB.15) carried out within the National Programme “Improvement of safety and working conditions” partly supported in Poland in 2020–2022—within the scope of research and development—by the National Centre for Research and Development were also included

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Aims: We aimed to determine the efficacy and safety of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists to prevent worsening urinary albumin-to-creatinine ratio as an early biomarker of diabetes kidney disease. Methods: A total of 178 patients with type 2 diabetes and obesity received combination treatment with SGLT2i added to GLP1ra (n = 76), GLP1ra added to SGLT2i (n = 50) or GLP1ra plus SGLT2i from start (n = 52), according to investigators´ best clinical judgement. Major outcomes assessed at 26 weeks were changes in urine albumintocreatinine-ratio (UACR), estimated glomerular filtration rate (eGFR), glycated haemoglobin, body weight and systolic blood pressure. Results: All patients (58.6% men, mean age 61.9 ± 10.0 years) completed the study. Baseline HbA1c, weight and eGFR levels were 8.2 ± 0.9%, 109.9 ± 19 kg and 83.3 ± 19.6 mL/min/m2 , respectively. At 26 weeks, we found significant reductions in HbA1c (1.16%), weight (5.17 kg) and systolic blood pressure (8.13 mmHg). The reduction in UACR was 15.14 mg/g (95% CI 8.50-22.4) (-24.6 ± 64.7%), which was greatest in the group of patients with SGLT2i added on to GLP1ra therapy (116.7 mg/g; 95% CI: 54-296.5 mg/g; P < .001. Patients with urinary albumin-to-creatinine ratio ≥30 mg/g, showed a higher declines (63.18 mg/g [95% CI 44.5-104.99]) (-56 ± 65.9%). The greatest reduction in urinary albumin-to-creatinine ratio was obtained when SGLT2i was added to GLP1ra (116.7 mg/g). The eGFR did not significantly change along the study period. Conclusion: Our results show the beneficial effect of GLP1ra and SGLT2i combination therapy on early biomarkers of diabetes kidney disease such as albuminuria and in other significant outcomes for diabetes control

Ancient Genomic Regulatory Blocks Are a Source for Regulatory Gene Deserts in Vertebrates after Whole-Genome Duplications

We investigated how the two rounds of whole genome duplication that occurred at the base of the vertebrate lineage have impacted ancient microsyntenic associations involving developmental regulators (known as genomic regulatory blocks, GRBs). We showed that the majority of GRBs identified in the last common ancestor of chordates have been maintained as a single copy in humans. We found evidence that dismantling of the duplicated GRB copies occurred early in vertebrate evolution often through the differential retention of the regulatory gene but loss of the bystander gene's exonic sequences. Despite the large evolutionary scale, the presence of duplicated highly conserved non-coding regions provided unambiguous proof for this scenario for multiple ancient GRBs. Remarkably, the dismantling of ancient GRB duplicates has contributed to the creation of large gene deserts associated with regulatory genes in vertebrates, providing a potentially widespread mechanism for the origin of these enigmatic genomic traits