Enhancement of the non-invasive electroenterogram to identify intestinal pacemaker activity

Surface recording of electroenterogram (EEnG) is a non-invasive method for monitoring intestinal myoelectrical activity. However, surface EEnG is seriously affected by a variety of interferences: cardiac activity, respiration, very low frequency components and movement artefacts. The aim of this study is to eliminate respiratory interference and very low frequency components from external EEnG recording by means of empirical mode decomposition (EMD), so as to obtain more robust indicators of intestinal pacemaker activity from external EEnG signal. For this purpose, 11 recording sessions were performed in an animal model under fasting conditions and in each individual session the myoelectrical signal was recorded simultaneously in the intestinal serosa and the external abdominal surface in physiological states. Various parameters have been proposed for evaluating the efficacy of the method in reducing interferences: the signal-to-interference ratio (S/I ratio), attenuation of the target and interference signals, the normal slow wave percentage and the stability of the dominant frequency (DF) of the signal. The results show that the S/I ratio of the processed signals is significantly greater than the original values (9.66±4.44 dB vs. 1.23±5.13 dB), while the target signal was barely attenuated (-0.63±1.02 dB). The application of the EMD method also increased the percentage of the normal slow wave to 100% in each individual session and enabled the stability of the DF of the external signal to be increased considerably. Furthermore, the variation coefficient of the DF derived from the external processed signals is comparable to the coefficient obtained using internal recordings. Therefore the EMD method could be a very useful tool to improve the quality of external EEnG recording in the low frequency range, and therefore to obtain more robust indicators of the intestinal pacemaker activity from non invasive EEnG recordingsThe authors would like to thank D Alvarez-Martinez, Dr C Vila and the Veterinary Unit of the Research Centre of 'La Fe' University Hospital (Valencia, Spain), where the surgical interventions and recording sessions were carried out, and the R+D+I Linguistic Assistance Office at the UPV for their help in revising this paper. This research study was sponsored by the Ministerio de Ciencia y Tecnologia de Espana (TEC2007-64278) and by the Universidad Politecnica de Valencia, as part of a UPV research and development Grant Programme.Ye Lin, Y.; Garcia Casado, FJ.; Prats Boluda, G.; Ponce, JL.; Martínez De Juan, JL. (2009). Enhancement of the non-invasive electroenterogram to identify intestinal pacemaker activity. PHYSIOLOGICAL MEASUREMENT. 30(9):885-902. https://doi.org/10.1088/0967-3334/30/9/002S885902309Amaris, M. A., Sanmiguel, C. P., Sadowski, D. C., Bowes, K. L., & Mintchev, M. P. (2002). Digestive Diseases and Sciences, 47(11), 2480-2485. doi:10.1023/a:1020503908304Bass, P., & Wiley, J. N. (1965). Electrical and extraluminal contractile-force activity of the duodenum of the dog. The American Journal of Digestive Diseases, 10(3), 183-200. doi:10.1007/bf02233747Bradshaw, L. A., Allos, S. H., Wikswo, J. P., & Richards, W. O. (1997). Correlation and comparison of magnetic and electric detection of small intestinal electrical activity. American Journal of Physiology-Gastrointestinal and Liver Physiology, 272(5), G1159-G1167. doi:10.1152/ajpgi.1997.272.5.g1159Camilleri, M., Hasler, W. L., Parkman, H. P., Quigley, E. M. M., & Soffer, E. (1998). Measurement of gastrointestinal motility in the GI laboratory. Gastroenterology, 115(3), 747-762. doi:10.1016/s0016-5085(98)70155-6Chen, J. D. Z., & Lin, Z. (1993). Adaptive cancellation of the respiratory artifact in surface recording of small intestinal electrical activity. Computers in Biology and Medicine, 23(6), 497-509. doi:10.1016/0010-4825(93)90097-kChen, J., & McCallum, R. W. (1991). Electrogastrography: measuremnt, analysis and prospective applications. Medical & Biological Engineering & Computing, 29(4), 339-350. doi:10.1007/bf02441653Chen, J. D. Z., Schirmer, B. D., & McCallum, R. W. (1993). Measurement of electrical activity of the human small intestine using surface electrodes. IEEE Transactions on Biomedical Engineering, 40(6), 598-602. doi:10.1109/10.237682Garcia-Casado, J., Martinez-de-Juan, J. L., & Ponce, J. L. (2005). Noninvasive Measurement and Analysis of Intestinal Myoelectrical Activity Using Surface Electrodes. IEEE Transactions on Biomedical Engineering, 52(6), 983-991. doi:10.1109/tbme.2005.846730Gordon, A. D. (1987). A Review of Hierarchical Classification. Journal of the Royal Statistical Society. Series A (General), 150(2), 119. doi:10.2307/2981629Huang, N. E., Shen, Z., Long, S. R., Wu, M. C., Shih, H. H., Zheng, Q., … Liu, H. H. (1998). The empirical mode decomposition and the Hilbert spectrum for nonlinear and non-stationary time series analysis. Proceedings of the Royal Society of London. Series A: Mathematical, Physical and Engineering Sciences, 454(1971), 903-995. doi:10.1098/rspa.1998.0193Irimia, A., & Bradshaw, L. A. (2005). Artifact reduction in magnetogastrography using fast independent component analysis. Physiological Measurement, 26(6), 1059-1073. doi:10.1088/0967-3334/26/6/015Lammers, W. J. E. P., & Stephen, B. (2008). Origin and propagation of individual slow waves along the intact feline small intestine. Experimental Physiology, 93(3), 334-346. doi:10.1113/expphysiol.2007.039180Liang, H. (2001). Adaptive independent component analysis of multichannel electrogastrograms. Medical Engineering & Physics, 23(2), 91-97. doi:10.1016/s1350-4533(01)00019-4Liang, J., Cheung, J. Y., & Chen, J. D. Z. (1997). Detection and deletion of motion artifacts in electrogastrogram using feature analysis and neural networks. Annals of Biomedical Engineering, 25(5), 850-857. doi:10.1007/bf02684169Liang, H., Lin, Z., & McCallum, R. W. (2000). Artifact reduction in electrogastrogram based on empirical mode decomposition method. Medical & Biological Engineering & Computing, 38(1), 35-41. doi:10.1007/bf02344686Zhi-Yue Lin, Chen, Z., & Jian De. (1994). Time-frequency representation of the electrogastrogram-application of the exponential distribution. IEEE Transactions on Biomedical Engineering, 41(3), 267-275. doi:10.1109/10.284945Lin, Z. Y., & Chen, J. D. Z. (1994). Recursive running DCT algorithm and its application in adaptive filtering of surface electrical recording of small intestine. Medical & Biological Engineering & Computing, 32(3), 317-322. doi:10.1007/bf02512529Lin, Z., & Chen, J. D. Z. (1995). Comparison of three running spectral analysis methods for electrogastrographic signals. Medical & Biological Engineering & Computing, 33(4), 596-604. doi:10.1007/bf02522520Maestri, R., Pinna, G. D., Porta, A., Balocchi, R., Sassi, R., Signorini, M. G., … Raczak, G. (2007). Assessing nonlinear properties of heart rate variability from short-term recordings: are these measurements reliable? Physiological Measurement, 28(9), 1067-1077. doi:10.1088/0967-3334/28/9/008Martinez-de-Juan, J. ., Saiz, J., Meseguer, M., & Ponce, J. . (2000). Small bowel motility: relationship between smooth muscle contraction and electroenterogram signal. Medical Engineering & Physics, 22(3), 189-199. doi:10.1016/s1350-4533(00)00032-1Mintchev, M. P., Kingma, Y. J., & Bowes, K. L. (1993). Accuracy of cutaneous recordings of gastric electrical activity. Gastroenterology, 104(5), 1273-1280. doi:10.1016/0016-5085(93)90334-9Prats-Boluda, G., Garcia-Casado, J., Martinez-de-Juan, J. L., & Ponce, J. L. (2007). Identification of the slow wave component of the electroenterogram from Laplacian abdominal surface recordings in humans. Physiological Measurement, 28(9), 1115-1133. doi:10.1088/0967-3334/28/9/012Quigley, E. M. M. (1996). GASTRIC AND SMALL INTESTINAL MOTILITY IN HEALTH AND DISEASE. Gastroenterology Clinics of North America, 25(1), 113-145. doi:10.1016/s0889-8553(05)70368-xSeidel, S. A., Bradshaw, L. A., Ladipo, J. K., Wikswo, J. P., & Richards, W. O. (1999). Noninvasive detection of ischemic bowel. Journal of Vascular Surgery, 30(2), 309-319. doi:10.1016/s0741-5214(99)70142-4Tomomasa, T., Morikawa, A., Sandler, R. H., Mansy, H. A., Koneko, H., Masahiko, T., … Itoh, Z. (1999). Gastrointestinal Sounds and Migrating Motor Complex in Fasted Humans. American Journal of Gastroenterology, 94(2), 374-381. doi:10.1111/j.1572-0241.1999.00862.xWang, Z. S., Cheung, J. Y., & Chen, J. D. Z. (1999). Blind separation of multichannel electrogastrograms using independent component analysis based on a neural network. Medical & Biological Engineering & Computing, 37(1), 80-86. doi:10.1007/bf0251327

A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future

© 2020 Pérez de Llano et al.Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) – understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis

Innovative Strategies for Ozone Treatment of Industrial Wastes: Hydrothermal Liquefaction of Surfactant Wastewater and Leacheate Evaporation

In this paper, ozonation is used as a pre-treatment for two different kinds of wastewaters. The first purpose is the study of the effect of ozonation on a landfill leachate treated by a reverse osmosis process prior a concentration step in an atmospheric evaporator. At first sight, an ozone treatment can supply three effects: Defoaming capacity, biocide effect, and pH acidifier to avoid the ammonia striping in the evaporation process. The second purpose of this paper is regarding hydrothermal liquefaction (HTL) of wastewaters. HTL can produce a liquid fuel, normally called crude-oil, alternative to fossil fuels, as well as other products of industrial interest (phenols, furfurals, etc.). The second objective is the study of the possible positive effect that a pre-treatment with ozone can have on the performance of the subsequent HTL. In this work, HTL is applied to liquid surfactant wastes obtaining up to 7% crude-oil yield, with a High Heating Value (HHV) higher than 8.000 cal/g. These results are compared with those obtained when an ozonation pre-treatment is applied before the HTL process. Ozone treatment shows a slight defoaming capacity for the leachate feed but don’t seem to show a significant difference in the HHV of the crude-oils obtained from liquid surfactant. However, there is a noticeable difference in the solid residue generated for this later. Less aggregates of solid particles and a weight reduction of 20% in the filtering step were obtained from ozonated liquid surfactants. The reduction of solid by-products is of great interest for dimensioning an industrial-scale HTL plant due to the problems that these solids can generate in pipes and valves

Impact of Sexualized Substance Use and Other Risk Practices on HCV Microelimination in gbMSM Living with HIV: Urgent Need for Targeted Strategies

In the original publication of the article, the article funding note was incorrectly published, the correct one should read as: This study has been funded by Instituto de Salud Carlos III through the project ‘‘PI18/00583’’ and co-funded by European Regional Development Fund ‘‘A way to make Europe’’. This has been corrected in this paper. © The Author(s) 2022

CoVITEST: A Fast and Reliable Method to Monitor Anti-SARS-CoV-2 Specific T Cells From Whole Blood

Cellular and humoral immune responses are essential for COVID-19 recovery and protection against SARS-CoV-2 reinfection. To date, the evaluation of SARS-CoV-2 immune protection has mainly focused on antibody detection, generally disregarding the cellular response, or placing it in a secondary position. This phenomenon may be explained by the complex nature of the assays needed to analyze cellular immunity compared with the technically simple and automated detection of antibodies. Nevertheless, a large body of evidence supports the relevance of the T cell's role in protection against SARS-CoV-2, especially in vulnerable individuals with a weakened immune system (such as the population over 65 and patients with immunodeficiencies). Here we propose to use CoVITEST (Covid19 anti-Viral Immunity based on T cells for Evaluation in a Simple Test), a fast, affordable and accessible in-house assay that, together with a diagnostic matrix, allows us to determine those patients who might be protected with SARS-CoV-2-reactive T cells. The method was established using healthy SARS-CoV-2-naïve donors pre- and post-vaccination (n=30), and further validated with convalescent COVID-19 donors (n=51) in a side-by-side comparison with the gold standard IFN-? ELISpot. We demonstrated that our CoVITEST presented reliable and comparable results to those obtained with the ELISpot technique in a considerably shorter time (less than 8 hours). In conclusion, we present a simple but reliable assay to determine cellular immunity against SARS-CoV-2 that can be used routinely during this pandemic to monitor the immune status in vulnerable patients and thereby adjust their therapeutic approaches. This method might indeed help to optimize and improve decision-making protocols for re-vaccination against SARS-CoV-2, at least for some population subsets.Copyright © 2022 Egri, Olivé, Hernández-Rodríguez, Castro, De Guzman, Heredia, Segura, Fernandez, de Moner, Torradeflot, Ballús, Martinez, Vazquez, Costa, Dobaño, Mazza, Mazzotti, Pascal, Juan, González-Navarro and Calderón

Do ART and chemsex drugs get along? Potential drug-drug Interactions in a cohort of people living with HIV who engaged in chemsex: a retrospective observational study.

Introduction: People living with HIV (PLWH) who engaged in chemsex are at risk of potential drug-drug interactions (pDDIs) with recreational drugs. This study aimed to characterize pDDIs between antiretroviral treatment (ART) and chemsex drugs and evaluate their association with unscheduled relevant hospital consultations. Methods: We conducted a single-center, retrospective, observational study in a series of gay, bisexual, and other men who have sex with men (gbMSM) living with HIV who engaged in chemsex and who attended a tertiary hospital in Barcelona, Spain, from February 2018 through August 2019. Associations between all recorded pDDIs and relevant unscheduled consultations were estimated using the incidence rate (IR) per 100 person-years of those events compared between patients with no pDDI (green flag) or moderate severity pDDI (orange flag) with patients with high severity pDDI (red flag) using the incidence rate ratio (IRR). Results: Among 172 PLWH engaged in chemsex, 249 ART regimens were prescribed: 44% based on integrase inhibitors, 30% on boosted ART, and 26% based on non-nucleoside reverse transcriptase inhibitors. The substances and recreational drugs most frequently used were erectile dysfunction agents (83%), methamphetamine (79%), GHB (77%), and alkyl nitrites (71%). Polydrug use was reported in 52%. We observed 2048 pDDIs. Of these, 23% were orange flag pDDIs; 88% related to boosted ARTs. The IR of the 285 unscheduled relevant episodes in patients with orange flag pDDIs was 64.67 (95% CI 40.07-89.28). The IRR of green flag pDDIs was 1.05 (95% CI 0.60-1.8; p = 0.876). Conclusion: One in four pDDIs were of moderate severity but no significant increase in the incidence of unscheduled relevant consultations was observed. A high number of unscheduled consultations, predominantly for psychiatric events and intoxication, were observed. Beyond using non-boosted ART to minimize pDDIs, other factors related to the practice of chemsex must be addressed, in order to offer a better approach

Effect of central nervous system (CNS) metastases in a real-world multicenter cohort study of Spanish ALK-positive non-small cell lung cancer (NSCLC) patients (p)

Background: CNS is a common site of metastases in patients with ALK-positive NSCLC. CNS metastases are associated with a number of deleterious effects, such as reduction in quality of life. However, the relationship between brain metastases and prognosis remains unclear. We aimed to evaluate the effect of CNS metastases on overall survival (OS) in a multicenter cohort of Spanish ALK-positive NSCLC patients diagnosed between 2008 and 2017. Methods: We included patients with stage IV at diagnoses, followed up to April 2018; OS (months [m]) was estimated with the Kaplan-Meier method. Survival curves were compared between groups of patients using the log-rank test. Hazard risk (HR) to death was estimated with multivariable Cox model. Results: Out of 163 patients in the cohort, a total of 116 were evaluated, with a median of follow-up of 29.2 m and 59 deaths reported. Characteristics at diagnosis were a median age of 58 years, 50% female, 58.6% never-smokers, 54.3% with comorbidities, PS by ECOG 0-1 93.1%. CNS metastases (median number of lesions 6) were present in 43.1% of patients and 34% of patients with CNS metastases were treated with local therapy (11.8 % local radiotherapy and 76.5% holocraneal radiotherapy). ALK inhibitors as first line and second line treatment were administered to 45.5% and 78.6% of patients, respectively. The median OS was 39 months; OS in patients with CNS metastases at diagnosis was 34.4 m and 39.0 m in those without CNS metastases at diagnosis (p=.9). In patients without CNS metastases at baseline (n=60), 22 developed CNS, with a median OS greater than in those without CNS metastases during follow-up, although the difference is not significant (45.5 m vs 33.3 m; p=.9). There were 81 patients who presented with metastases in more than one organ and 33 patients with metastases in a single organ. The risk of death increased as the number of metastatic organs at diagnoses increased (HR=1.26, p=.0305), with worse OS in those presenting with liver metastases at diagnoses (21.1%, OS: 20 m), compared to those without tumor involvement (OS: 45.4 m; p =.008). Conclusions: OS was similar for ALK-positive NSCLC patients with and without CNS metastases at diagnoses. OS was worse as the number of metastatic organs at diagnosis increased, with liver metastases being associated with the highest risk of mortality

Pharmacokinetic/pharmacodynamic integration and modelling of florfenicol for the pig pneumonia pathogens Actinobacillus pleuropneumoniae and Pasteurella multocida

Pharmacokinetic-pharmacodynamic (PK/PD) integration and modelling were used to predict dosage schedules for florfenicol for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Pharmacokinetic data were pooled for two bioequivalent products, pioneer and generic formulations, administered intramuscularly to pigs at a dose rate of 15 mg/kg. Antibacterial potency was determined in vitro as minimum inhibitory concentration (MIC) and Mutant Prevention Concentration in broth and pig serum, for six isolates of each organism. For both organisms and for both serum and broth MICs, average concentration:MIC ratios over 48 h were similar and exceeded 2.5:1 and times greater than MIC exceeded 35 h. From in vitro time-kill curves, PK/PD modelling established serum breakpoint values for the index AUC24h/MIC for three levels of inhibition of growth, bacteriostasis and 3 and 4log10 reductions in bacterial count; means were 25.7, 40.2 and 47.0 h, respectively, for P. multocida and 24.6, 43.8 and 58.6 h for A. pleuropneumoniae. Using these PK and PD data, together with literature MIC distributions, doses for each pathogen were predicted for: (1) bacteriostatic and bactericidal levels of kill; (2) for 50 and 90% target attainment rates (TAR); and (3) for single dosing and daily dosing at steady state. Monte Carlo simulations for 90% TAR predicted single doses to achieve bacteriostatic and bactericidal actions over 48 h of 14.4 and 22.2 mg/kg (P. multocida) and 44.7 and 86.6 mg/kg (A. pleuropneumoniae). For daily doses at steady state, and 90% TAR bacteriostatic and bactericidal actions, dosages of 6.2 and 9.6 mg/kg (P. multocida) and 18.2 and 35.2 mg/kg (A. pleuropneumoniae) were required. PK/PD integration and modelling approaches to dose determination indicate the possibility of tailoring dose to a range of end-points

Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry : A bridge to individualized medicine

Background We have evaluated the ex vivo pharmacology of single drugs and drug combinations in malignant cells of bone marrow samples from 125 patients with acute myeloid leukemia using a novel automated flow cytometry-based platform (ExviTech). We have improved previous ex vivo drug testing with 4 innovations: identifying individual leukemic cells, using intact whole blood during the incubation, using an automated platform that escalates reliably data, and performing analyses pharmacodynamic population models. Patients and Methods Samples were sent from 24 hospitals to a central laboratory and incubated for 48 hours in whole blood, after which drug activity was measured in terms of depletion of leukemic cells. Results The sensitivity of single drugs is assessed for standard efficacy (E) and potency (EC) variables, ranked as percentiles within the population. The sensitivity of drug-combination treatments is assessed for the synergism achieved in each patient sample. We found a large variability among patient samples in the dose-response curves to a single drug or combination treatment. Conclusion We hypothesize that the use of the individual patient ex vivo pharmacological profiles may help to guide a personalized treatment selection. © 2014 The Authors. Published by Elsevier Inc. All rights reserved