Floppy closing door epiglottis treated successfully with an mhealth application based on myofunctional therapy: a case report

We introduce the first case reported to date of a floppy closing door epiglottis in an OSA (obstructive sleep apnea) patient treated successfully with an Mhealth smartphone application based on myofunctional therapy

Electrohysterogram for ANN-Based Prediction of Imminent Labor in Women with Threatened Preterm Labor Undergoing Tocolytic Therapy

[EN] Threatened preterm labor (TPL) is the most common cause of hospitalization in the second half of pregnancy and entails high costs for health systems. Currently, no reliable labor proximity prediction techniques are available for clinical use. Regular checks by uterine electrohysterogram (EHG) for predicting preterm labor have been widely studied. The aim of the present study was to assess the feasibility of predicting labor with a 7- and 14-day time horizon in TPL women, who may be under tocolytic treatment, using EHG and/or obstetric data. Based on 140 EHG recordings, artificial neural networks were used to develop prediction models. Non-linear EHG parameters were found to be more reliable than linear for differentiating labor in under and over 7/14 days. Using EHG and obstetric data, the <7- and <14-day labor prediction models achieved an AUC in the test group of 87.1 +/- 4.3% and 76.2 +/- 5.8%, respectively. These results suggest that EHG can be reliable for predicting imminent labor in TPL women, regardless of the tocolytic therapy stage. This paves the way for the development of diagnostic tools to help obstetricians make better decisions on treatments, hospital stays and admitting TPL women, and can therefore reduce costs and improve maternal and fetal wellbeing.This work was supported by the Spanish Ministry of Economy and Competitiveness, the European Regional Development Fund (MCIU/AEI/FEDER, UE RTI2018-094449-A-I00-AR) and by the Generalitat Valenciana (AICO/2019/220).Mas-Cabo, J.; Prats-Boluda, G.; Garcia-Casado, J.; Alberola Rubio, J.; Monfort-Ortiz, R.; Martinez-Saez, C.; Perales, A.... (2020). Electrohysterogram for ANN-Based Prediction of Imminent Labor in Women with Threatened Preterm Labor Undergoing Tocolytic Therapy. 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Evaluation of monocytes as carriers for armed oncolytic adenoviruses in murine and Syrian hamster models of cancer

Replication-competent (oncolytic) adenoviruses (OAV) can be adapted as vectors for the delivery of therapeutic genes, with the aim of extending the antitumor effect beyond direct cytolysis. Transgene expression using these vectors is usually intense but short-lived, and repeated administrations are hampered by the rapid appearance of neutralizing antibodies (NAbs). We have studied the performance of monocytes as cell carriers to improve transgene expression in cancer models established in athymic mice and immunocompetent Syrian hamsters. Human and hamster monocytic cell lines (MonoMac6 and HM-1, respectively) were loaded with replication-competent adenovirus-expressing luciferase. Intravenous administration of these cells caused a modest increase in transgene expression in tumor xenografts, but this effect was virtually lost in hamsters. In contrast, intratumoral administration of HM-1 cells allowed repeated cycles of expression and achieved partial protection from NAbs in preimmunized hamsters bearing pancreatic tumors. To explore the therapeutic potential of this approach, HM-1 cells were loaded with a hypoxia-inducible OAV expressing the immunostimulatory cytokine interleukin-12 (IL-12). Three cycles of treatment achieved a significant antitumor effect in the hamster model, and transgene expression was detected following each administration, in contrast with the rapid neutralization of the free virus. We propose monocytes as carriers for multiple intratumoral administrations of armed OAVs

Active flexible concentric ring electrode for non-invasive surface bioelectrical recordings

Bioelectrical surface recordings are usually performed by unipolar or bipolar disc electrodes even though they entail the serious disadvantage of having poor spatial resolution. Concentric ring electrodes give improved spatial resolution, although this type of electrode has so far only been implemented in rigid substrates and as they are not adapted to the curvature of the recording surface may provide discomfort to the patient. Moreover, the signals recorded by these electrodes are usually lower in amplitude than conventional disc electrodes. The aim of this work was thus to develop and test a new modular active sensor made up of concentric ring electrodes printed on a flexible substrate by thick-film technology together with a reusable battery-powered signal-conditioning circuit. Simultaneous ECG recording with both flexible and rigid concentric ring electrodes was carried out on ten healthy volunteers at rest and in motion. The results show that flexible concentric ring electrodes not only present lower skin electrode contact impedance and lower baseline wander than rigid electrodes but are also less sensitive to interference and motion artefacts. We believe these electrodes, which allow bioelectric signals to be acquired non-invasively with better spatial resolution than conventional disc electrodes, to be a step forward in the development of new monitoring systems based on Laplacian potential recordings.This research was supported in part by the Ministerio de Ciencia y Tecnologia de Espana (TEC2010-16945) and by the Universitat Politecnica de Valencia (PAID 2009/10-2298). The proof-reading of this paper was funded by the Universitat Politecnica de Valencia, Spain.Prats Boluda, G.; Ye Lin, Y.; García Breijo, E.; Ibáñez Civera, FJ.; Garcia Casado, FJ. (2012). Active flexible concentric ring electrode for non-invasive surface bioelectrical recordings. 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Brain Topography, 8(4), 355-366. doi:10.1007/bf01186911Farina, D., & Cescon, C. (2001). Concentric-ring electrode systems for noninvasive detection of single motor unit activity. IEEE Transactions on Biomedical Engineering, 48(11), 1326-1334. doi:10.1109/10.959328G. Besio, C. C. Lu, P. P. Tarjan, W. (2001). A Feasibility Study for Body Surface Cardiac Propagation Maps of Humans from Laplacian Moments of Activation. Electromagnetics, 21(7-8), 621-632. doi:10.1080/027263401752246243Li, G., Wang, Y., Lin, L., Jiang, W., Wang, L. L., Lu, S. C.-Y., & Besio, W. G. (2005). Active Laplacian electrode for the data-acquisition system of EHG. Journal of Physics: Conference Series, 13, 330-335. doi:10.1088/1742-6596/13/1/077Engel, J., Chen, J., & Liu, C. (2003). Development of polyimide flexible tactile sensor skin. Journal of Micromechanics and Microengineering, 13(3), 359-366. doi:10.1088/0960-1317/13/3/302Papakostas, T. V., Lima, J., & Lowe, M. (s. f.). A large area force sensor for smart skin applications. Proceedings of IEEE Sensors. doi:10.1109/icsens.2002.1037366Stieglitz, T. (2001). Flexible biomedical microdevices with double-sided electrode arrangements for neural applications. Sensors and Actuators A: Physical, 90(3), 203-211. doi:10.1016/s0924-4247(01)00520-9Hamilton, P. S., & Tompkins, W. J. (1986). Quantitative Investigation of QRS Detection Rules Using the MIT/BIH Arrhythmia Database. IEEE Transactions on Biomedical Engineering, BME-33(12), 1157-1165. doi:10.1109/tbme.1986.325695Besio, W., & Chen, T. (2007). Tripolar Laplacian electrocardiogram and moment of activation isochronal mapping. Physiological Measurement, 28(5), 515-529. doi:10.1088/0967-3334/28/5/006Besio, G., Koka, K., Aakula, R., & Weizhong Dai. (2006). Tri-polar concentric ring electrode development for Laplacian electroencephalography. IEEE Transactions on Biomedical Engineering, 53(5), 926-933. doi:10.1109/tbme.2005.863887Setti, L., Fraleoni-Morgera, A., Ballarin, B., Filippini, A., Frascaro, D., & Piana, C. (2005). An amperometric glucose biosensor prototype fabricated by thermal inkjet printing. Biosensors and Bioelectronics, 20(10), 2019-2026. doi:10.1016/j.bios.2004.09.022Reddy, A. S. G., Narakathu, B. B., Atashbar, M. Z., Rebros, M., Rebrosova, E., & Joyce, M. K. (2011). Gravure Printed Electrochemical Biosensor. Procedia Engineering, 25, 956-959. doi:10.1016/j.proeng.2011.12.235Gruetzmann, A., Hansen, S., & Müller, J. (2007). Novel dry electrodes for ECG monitoring. Physiological Measurement, 28(11), 1375-1390. doi:10.1088/0967-3334/28/11/005LI, G., LIAN, J., SALLA, P., CHENG, J., RAMACHANDRA, I., SHAH, P., … HE, B. (2003). Body Surface Laplacian Electrocardiogram of Ventricular Depolarization in Normal Human Subjects. 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Histological and ultrastructural comparison of cauterization and thrombosis stroke models in immune-deficient mice

Background: Stroke models are essential tools in experimental stroke. Although several models of stroke have been developed in a variety of animals, with the development of transgenic mice there is the need to develop a reliable and reproducible stroke model in mice, which mimics as close as possible human stroke. Methods: BALB/Ca-RAG2-/-gc-/- mice were subjected to cauterization or thrombosis stroke model and sacrificed at different time points (48hr, 1wk, 2wk and 4wk) after stroke. Mice received BrdU to estimate activation of cell proliferation in the SVZ. Brains were processed for immunohistochemical and EM. Results: In both stroke models, after inflammation the same glial scar formation process and damage evolution takes place. After stroke, necrotic tissue is progressively removed, and healthy tissue is preserved from injury through the glial scar formation. Cauterization stroke model produced unspecific damage, was less efficient and the infarct was less homogeneous compared to thrombosis infarct. Finally, thrombosis stroke model produces activation of SVZ proliferation. Conclusions: Our results provide an exhaustive analysis of the histopathological changes (inflammation, necrosis, tissue remodeling, scarring...) that occur after stroke in the ischemic boundary zone, which are of key importance for the final stroke outcome. This analysis would allow evaluating how different therapies would affect wound and regeneration. Moreover, this stroke model in RAG 2-/- gC -/- allows cell transplant from different species, even human, to be analyzed

Analysis of human cerebrospinal fluid monoamines and their cofactors by HPLC

The presence of monoamines and their cofactors (the pterins and vitamin B6 (pyridoxal phosphate (PLP))) in human cerebrospinal fluid (CSF) can be used as indicators of the biosynthesis and turnover of dopamine and serotonin in the brain. In addition, abnormalities in the CSF levels of these molecules are associated with various neurological diseases, including genetic diseases leading to dopamine and serotonin deficiency. Here, we provide a set of quantitative high-performance liquid-chromatography (HPLC) approaches to determine CSF levels of monoamines and their cofactors. This protocol describes step-by-step procedures for CSF sample preparation for the analysis of different molecules, HPLC calibration and analysis, and data quantification and interpretation. Unlike plasma/tissue/blood samples, CSF requires minimal sample preparation: in this protocol, only the analysis of PLP requires mixing with trichloroacetic acid to release the protein-bound vitamin, centrifugation, and mixing of the supernatant with phosphate buffer and sodium cyanide for derivatization in alkaline conditions. Monoamines are analyzed by HPLC with coulometric electrochemical detection (ED), pterins are analyzed by HPLC with coupled coulometric electrochemical and fluorescence detection, and PLP is analyzed by HPLC with fluorescence detection. The quantification of all compounds is achieved by external calibration procedures, and internal quality control and standards are analyzed in each run. We anticipate that investigation of dopamine and serotonin disturbances will be facilitated by measurements of these compounds in human CSF and other biological samples. The estimated time for the different procedures primarily depends on the electrochemical detector stabilization. Overnight stabilization of this detector is advised, and, after that step, preanalytical equilibration rarely exceeds 3 h

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p&lt;0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p&lt;0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p&lt;0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology