Comparison of electrohysterogram signal measured by surface electrodes with different designs: A computational study with dipole band and abdomen models

Non-invasive measurement of uterine activity using electrohysterogram (EHG) surface electrodes has been attempted to monitor uterine contraction. This study aimed to computationally compare the performance of acquiring EHG signals using monopolar electrode and three types of Laplacian concentric ring electrodes (bipolar, quasi-bipolar and tri-polar). With the implementation of dipole band model and abdomen model, the performances of four electrodes in terms of the local sensitivity were quantifed by potential attenuation. Furthermore, the efects of fat and muscle thickness on potential attenuation were evaluated using the bipolar and tri-polar electrodes with diferent radius. The results showed that all the four types of electrodes detected the simulated EHG signals with consistency. That the bipolar and tri-polar electrodes had greater attenuations than the others, and the shorter distance between the origin and location of dipole band at 20dB attenuation, indicating that they had relatively better local sensitivity. In addition, ANOVA analysis showed that, for all the electrodes with diferent outer ring radius, the efects of fat and muscle on potential attenuation were signifcant (all p<0.01). It is therefore concluded that the bipolar and tri-polar electrodes had higher local sensitivity than the others, indicating that they can be applied to detect EHG efectively

Feasibility and analysis of bipolar concentric recording of Electrohysterogram with flexible active electrode

The conduction velocity and propagation patterns of Electrohysterogram (EHG) provide fundamental information about uterine electrophysiological condition. The accuracy of these measurements can be impaired by both the poor spatial selectivity and sensitivity to the relative direction of the contraction propagation associated with conventional disc electrodes. Concentric ring electrodes could overcome these limitations the aim of this study was to examine the feasibility of picking up surface EHG signals using a new flexible tripolar concentric ring electrode (TCRE), and to compare it with conventional bipolar recordings. Simultaneous recording of conventional bipolar signals and bipolar concentric EHG (BC-EHG) were carried out on 22 pregnant women. Signal bursts were characterized and compared. No significant differences among channels in either duration or dominant frequency in the Fast Wave High frequency range were found. Nonetheless, the high pass filtering effect of the BC-EHG records resulted in lower frequency content within the range 0.1 to 0.2 Hz than the bipolar ones. Although the BC-EHG signal amplitude was about 5-7 times smaller than that of bipolar recordings, similar signal-to-noise ratio was obtained. These results suggest that the flexible TCRE is able to pick up uterine electrical activity and could provide additional information for deducing uterine electrophysiological condition.The authors are grateful to the Obstetrics Unit of the Hospital Universitario La Fe de Valencia (Valencia, Spain), where the recording sessions were carried out. The work was supported in part by the Ministerio de Ciencia y Tecnologia de Espana (TEC2010-16945), by the Universitat Politecnica de Valencia (PAID SP20120490) and Generalitat Valenciana (GV/2014/029) and by General Electric Healthcare.Ye Lin, Y.; Alberola Rubio, J.; Prats Boluda, G.; Perales Marin, AJ.; Desantes, D.; Garcia Casado, FJ. (2015). Feasibility and analysis of bipolar concentric recording of Electrohysterogram with flexible active electrode. Annals of Biomedical Engineering. 43(4):968-976. https://doi.org/10.1007/s10439-014-1130-5S968976434Alberola-Rubio, J., G. Prats-Boluda, Y. Ye-Lin, J. Valero, A. Perales, and J. Garcia-Casado. Comparison of non-invasive electrohysterographic recording techniques for monitoring uterine dynamics. Med. Eng. Phys. 35(12):1736–1743, 2013.Besio, W. G., K. Koka, R. Aakula, and W. Dai. Tri-polar concentric ring electrode development for laplacian electroencephalography. IEEE Trans. Biomed. Eng. 53(5):926–933, 2006.Devasahayam, S. R. Signals and Systems in Biomedical Engineering. Berlin: Springer, 2013.Devedeux, D., C. Marque, S. Mansour, G. Germain, and J. Duchene. Uterine electromyography: a critical review. Am. J. Obstet. Gynecol. 169(6):1636–1653, 1993.Estrada, L., A. Torres, J. Garcia-Casado, G. Prats-Boluda, and R. Jane. Characterization of laplacian surface electromyographic signals during isometric contraction in biceps brachii. Conf. Proc. IEEE Eng Med. Biol. Soc. 2013:535–538, 2013.Euliano, T. Y., D. Marossero, M. T. Nguyen, N. R. Euliano, J. Principe, and R. K. Edwards. Spatiotemporal electrohysterography patterns in normal and arrested labor. Am. J. Obstet. Gynecol. 200(1):54–57, 2009.Farina, D., and C. Cescon. Concentric-ring electrode systems for noninvasive detection of single motor unit activity. IEEE Trans. Biomed. Eng. 48(11):1326–1334, 2001.Fele-Zorz, G., G. Kavsek, Z. Novak-Antolic, and F. Jager. A comparison of various linear and non-linear signal processing techniques to separate uterine EMG records of term and pre-term delivery groups. Med. Biol. Eng Comput. 46(9):911–922, 2008.Garfield, R. E., and W. L. Maner. Physiology and electrical activity of uterine contractions. Semin. Cell Dev. Biol. 18(3):289–295, 2007.Garfield, R. E., W. L. Maner, L. B. Mackay, D. Schlembach, and G. R. Saade. Comparing uterine electromyography activity of antepartum patients vs. term labor patients. Am. J. Obstet. Gynecol. 193(1):23–29, 2005.Garfield, R. E., H. Maul, L. Shi, W. Maner, C. Fittkow, G. Olsen, and G. R. Saade. Methods and devices for the management of term and preterm labor. Ann. N. Y. Acad. Sci. 943(1):203–224, 2001.Hassan, M., J. Terrien, C. Muszynski, A. Alexandersson, C. Marque, and B. Karlsson. Better pregnancy monitoring using nonlinear correlation analysis of external uterine electromyography. IEEE Trans. Biomed. Eng. 60(4):1160–1166, 2013.Kaufer, M., L. Rasquinha, and P. Tarjan. Optimization of multi-ring sensing electrode set, Conference proceedings of IEEE Engineering in Medicine and Biology Society, 1990, pp. 612–613.Koka, K., and W. G. Besio. Improvement of spatial selectivity and decrease of mutual information of tri-polar concentric ring electrodes. J. Neurosci. Methods 165(2):216–222, 2007.Lu, C.-C., and P. P. Tarjan. Pasteless, active, concentric ring sensors for directly obtained laplacian cardiac electrograms. J. Med. Biol. Eng. 22(4):199–203, 2002.Lucovnik, M., W. L. Maner, L. R. Chambliss, R. Blumrick, J. Balducci, Z. Novak-Antolic, and R. E. Garfield. Noninvasive uterine electromyography for prediction of preterm delivery. Am. J. Obstet. Gynecol. 204(3):228.e1–228.e10, 2011.Maner, W. L., and R. E. Garfield. Identification of human term and preterm labor using artificial neural networks on uterine electromyography data. Ann. Biomed. Eng. 35(3):465–473, 2007.Maner, W. L., R. E. Garfield, H. Maul, G. Olson, and G. Saade. Predicting term and preterm delivery with transabdominal uterine electromyography. Obstet. Gynecol. 101(6):1254–1260, 2003.Marque, C., J. M. Duchene, S. Leclercq, G. S. Panczer, and J. Chaumont. Uterine EHG processing for obstetrical monitoring. IEEE Trans. Biomed. Eng. 33(12):1182–1187, 1986.Marque, C. K., J. Terrien, S. Rihana, and G. Germain. Preterm labour detection by use of a biophysical marker: the uterine electrical activity. BMC. Pregnancy Childbirth. 7(Suppl1):S5, 2007.Maul, H., W. L. Maner, G. Olson, G. R. Saade, and R. E. Garfield. Non-invasive transabdominal uterine electromyography correlates with the strength of intrauterine pressure and is predictive of labor and delivery. J. Matern. Fetal Neonatal Med. 15(5):297–301, 2004.Miles, A. M., M. Monga, and K. S. Richeson. Correlation of external and internal monitoring of uterine activity in a cohort of term patients. Am. J. Perinatol. 18(3):137–140, 2001.Prats-Boluda, G., J. Garcia-Casado, J. L. Martinez-de-Juan, and Y. Ye-Lin. Active concentric ring electrode for non-invasive detection of intestinal myoelectric signals. Med. Eng. Phys. 33(4):446–455, 2010.Prats-Boluda, G., Y. Ye-Lin, E. Garcia-Breijo, J. Ibañez, and J. Garcia-Casado. Active flexible concentric ring electrode for non-invasive surface bioelectrical recordings. Meas. Sci. Technol. 23(12):1–10, 2012.Rabotti, C., M. Mischi, S. G. Oei, and J. W. Bergmans. Noninvasive estimation of the electrohysterographic action-potential conduction velocity. IEEE Trans. Biomed. Eng. 57(9):2178–2187, 2010.Rabotti, C., S. G. Oei, H. J. van ‘t, and M. Mischi. Electrohysterographic propagation velocity for preterm delivery prediction. Am. J. Obstet. Gynecol. 205(6):e9–e10, 2011.Rooijakkers, M. J., S. Song, C. Rabotti, S. G. Oei, J. W. Bergmans, E. Cantatore, and M. Mischi. Influence of electrode placement on signal quality for ambulatory pregnancy monitoring. Comput. Math. Methods Med. 2014(1):960980, 2014.Schlembach, D., W. L. Maner, R. E. Garfield, and H. Maul. Monitoring the progress of pregnancy and labor using electromyography. Eur. J. Obstet. Gynecol. Reprod. Biol. 144(Suppl1):S33–S39, 2009.Sikora, J., A. Matonia, R. Czabanski, K. Horoba, J. Jezewski, and T. Kupka. Recognition of premature threatening labour symptoms from bioelectrical uterine activity signals. Arch. Perinatal Med. 17(2):97–103, 2011.Terrien, J., C. Marque, and B. Karlsson. Spectral characterization of human EHG frequency components based on the extraction and reconstruction of the ridges in the scalogram, Conference proceedings of IEEE Engineering in Medicine and Biology Society, 2007, pp. 1872–1875.Terrien, J., C. Marque, T. Steingrimsdottir, and B. Karlsson. Evaluation of adaptive filtering methods on a 16 electrode electrohysterogram recorded externally in labor, 11th Mediterranean Conference on Medical and Biomedical Engineering and Computing, 2007, Vol. 16, pp. 135–138.U.S. Preventive Services Task Force. Guide to clinical preventive services: an assessment of the effectiveness of 169 interventions. Baltimore: Willams & Wilkins, 1989

Internally coupled ears in living mammals.

It is generally held that the right and left middle ears of mammals are acoustically isolated from each other, such that mammals must rely on neural computation to derive sound localisation cues. There are, however, some unusual species in which the middle ear cavities intercommunicate, in which case each ear might be able to act as a pressure-difference receiver. This could improve sound localisation at lower frequencies. The platypus Ornithorhynchus is apparently unique among mammals in that its tympanic cavities are widely open to the pharynx, a morphology resembling that of some non-mammalian tetrapods. The right and left middle ear cavities of certain talpid and golden moles are connected through air passages within the basicranium; one experimental study on Talpa has shown that the middle ears are indeed acoustically coupled by these means. Having a basisphenoid component to the middle ear cavity walls could be an important prerequisite for the development of this form of interaural communication. Little is known about the hearing abilities of platypus, talpid and golden moles, but their audition may well be limited to relatively low frequencies. If so, these mammals could, in principle, benefit from the sound localisation cues available to them through internally coupled ears. Whether or not they actually do remains to be established experimentally.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00422-015-0675-

The soluble guanylate cyclase activator cinaciguat prevents cardiac dysfunction in a rat model of type-1 diabetes mellitus

BACKGROUND: Diabetes mellitus (DM) leads to the development of diabetic cardiomyopathy, which is associated with altered nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signalling. Cardioprotective effects of elevated intracellular cGMP-levels have been described in different heart diseases. In the current study we aimed at investigating the effects of pharmacological activation of sGC in diabetic cardiomyopathy. METHODS: Type-1 DM was induced in rats by streptozotocin. Animals were treated either with the sGC activator cinaciguat (10 mg/kg/day) or with placebo orally for 8 weeks. Left ventricular (LV) pressure-volume (P-V) analysis was used to assess cardiac performance. Additionally, gene expression (qRT-PCR) and protein expression analysis (western blot) were performed. Cardiac structure, markers of fibrotic remodelling and DNA damage were examined by histology, immunohistochemistry and TUNEL assay, respectively. RESULTS: DM was associated with deteriorated cGMP signalling in the myocardium (elevated phosphodiesterase-5 expression, lower cGMP-level and impaired PKG activity). Cardiomyocyte hypertrophy, fibrotic remodelling and DNA fragmentation were present in DM that was associated with impaired LV contractility (preload recruitable stroke work (PRSW): 49.5 +/- 3.3 vs. 83.0 +/- 5.5 mmHg, P < 0.05) and diastolic function (time constant of LV pressure decay (Tau): 17.3 +/- 0.8 vs. 10.3 +/- 0.3 ms, P < 0.05). Cinaciguat treatment effectively prevented DM related molecular, histological alterations and significantly improved systolic (PRSW: 66.8 +/- 3.6 mmHg) and diastolic (Tau: 14.9 +/- 0.6 ms) function. CONCLUSIONS: Cinaciguat prevented structural, molecular alterations and improved cardiac performance of the diabetic heart. Pharmacological activation of sGC might represent a new therapy approach for diabetic cardiomyopathy

Learning horizon and optimal alliance formation

We develop a theoretical Bayesian learning model to examine how a firm’s learning horizon, defined as the maximum distance in a network of alliances across which the firm learns from other firms, conditions its optimal number of direct alliance partners under technological uncertainty. We compare theoretical optima for a ‘close’ learning horizon, where a firm learns only from direct alliance partners, and a ‘distant’ learning horizon, where a firm learns both from direct and indirect alliance partners. Our theory implies that in high tech industries, a distant learning horizon allows a firm to substitute indirect for direct partners, while in low tech industries indirect partners complement direct partners. Moreover, in high tech industries, optimal alliance formation is less sensitive to changes in structural model parameters when a firm’s learning horizon is distant rather than close. Our contribution lies in offering a formal theory of the role of indirect partners in optimal alliance portfolio design that generates normative propositions amenable to future empirical refutation

Prevalence, Features and Risk Factors for Malaria Co-Infections amongst Visceral Leishmaniasis Patients from Amudat Hospital, Uganda

Visceral leishmaniasis (VL) and malaria are two major parasitic diseases sharing a similar demographic and geographical distribution. In areas where both diseases are endemic, such as Sudan, Uganda, India and Bangladesh, co-infection cases have been reported, but features and risk factors associated with these co-morbidities remain poorly characterized. In the present study, routinely collected data of VL patients admitted to Amudat Hospital, Uganda, were used to investigate the magnitude of VL-malaria co-infections and identify possible risk factors. Nearly 20% of the patients included in this study were found to be co-infected with VL and malaria, indicating that this is a common condition among VL patients living in malaria endemic areas. Young age (≤9 years) was identified as an important risk factor for contracting the VL-malaria co-infection, while being anemic or carrying a skin infection appeared to negatively correlate with the co-morbidity. Co-infected patients presented with slightly more severe symptoms compared to mono-infected patients, but had a similar prognosis, possibly due to early diagnosis of malaria as a result of systematic testing. In conclusion, these results emphasize the importance of performing malaria screening amongst VL patients living in malaria-endemic areas and suggest that close monitoring of co-infected patients should be implemented

Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: The role of p38 MAPK and ROS

Due to narrow therapeutic window of cancer therapeutic agents and the development of resistance against these agents, there is a need to discover novel agents to treat breast cancer. The antitumor activities of thymoquinone (TQ), a compound isolated from Nigella sativa oil, were investigated in breast carcinoma in vitro and in vivo. Cell responses after TQ treatment were assessed by using different assays including MTT assay, annexin V-propidium iodide staining, Mitosox staining and Western blot. The antitumor effect was studied by breast tumor xenograft mouse model, and the tumor tissues were examined by histology and immunohistochemistry. The level of antioxidant enzymes/molecules in mouse liver tissues was measured by commercial kits. Here, we show that TQ induced p38 phosphorylation and ROS production in breast cancer cells. These inductions were found to be responsible for TQ’s anti-proliferative and pro-apoptotic effects. Moreover, TQ-induced ROS production regulated p38 phosphorylation but not vice versa. TQ treatment was found to suppress the tumor growth and this effect was further enhanced by combination with doxorubicin. TQ also inhibited the protein expression of anti-apoptotic genes, such as XIAP, survivin, Bcl-xL and Bcl-2, in breast cancer cells and breast tumor xenograft. Reduced Ki67 and increased TUNEL staining were observed in TQ-treated tumors. TQ was also found to increase the level of catalase, superoxide dismutase and glutathione in mouse liver tissues. Overall, our results demonstrated that the antiproliferative and pro-apoptotic effects of TQ in breast cancer are mediated through p38 phosphorylation via ROS generation

Global Analysis of the Impact of Environmental Perturbation on cis-Regulation of Gene Expression

Genetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent by which controlled, environmental perturbation influences cis-eQTLs is unclear. We carried out large-scale induction experiments using primary human bone cells derived from unrelated donors of Swedish origin treated with 18 different stimuli (7 treatments and 2 controls, each assessed at 2 time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t = 2h), dexamethasone (DEX) (t = 24h), and PGE2 (t = 24h). Using these treatments and control, we performed expression profiling for 18,144 RefSeq transcripts on biological replicates of the complete study cohort of 113 individuals (ntotal = 782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs (defined as SNPs located within the gene ±250 kb). We found that 93% of cis-eQTLs at 1% FDR were observed in at least one additional treatment, and in fact, on average, only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment. Treatment-specific cis-regulatory effects were, however, 2- to 6-fold more abundant among differently expressed genes upon treatment. We further followed-up and validated the DEX–specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 kb and 250 kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interactions between cellular environment and cis-variants are relatively rare (∼1.5%), but that detection of such specific interactions can be achieved by a combination of functional genomic approaches as described here