Computational Study of the Effect of Electrode Polarity on Neural Activation Related to Paresthesia Coverage in Spinal Cord Stimulation Therapy

[EN] Objective: Using computer simulation, we investigated the effect of electrode polarity on neural activation in spinal cord stimulation and propose a new strategy to maximize the activating area in the dorsal column (DC) and, thus, paresthesia coverage in clinical practice. Materials and Methods: A new three-dimensional spinal cord model at the T10 vertebral level was developed to simulate neural activation induced by the electric field distribution produced by different typical four-contact electrode polarities in single- and dual-lead stimulation. Our approach consisted of the combination of a finite element model of the spinal cord developed in COMSOL Multiphysics and a nerve fiber model implemented in MATLAB. Five evaluation parameters were evaluated, namely, the recruitment ratio, the perception and discomfort thresholds, and the activating area and depth. The results were compared quantitatively. Results: The dual-guarded cathode presents the maximum activating area and depth in single- and dual-lead stimulation. However, the lowest value of the ratio between the perception threshold in DC and the perception threshold in the dorsal root (DR) is achieved when the guarded cathode is programmed. Although the two versions of bipolar polarity (namely bipolar 1 and bipolar 2) produce higher activating area and depth than the guarded cathode, they are suitable for producing DR stimulation. Similarly, dual-lead stimulation is likely to activate DR fibers because the electrodes are closer to these fibers. Conclusions: The results suggest that the activating area in the DC is maximized by using the dual-guarded cathode both in single- and dual-lead stimulation modes. However, DC nerve fibers are preferentially stimulated when the guarded cathode is used. According to these results, the new electrode programming strategy that we propose for clinical practice first uses the dual-guarded cathode, but, if the DR nerve fibers are activated, it then uses guarded cathode polarity.The authors thank Virginie Callot for providing us with all the spinal cord measurements from her research group’s study. The authors would like also to thank Surgicen S.L. for providing financial assistanceDurá, JL.; Solanes, C.; De Andrés, J.; Saiz Rodríguez, FJ. (2019). Computational Study of the Effect of Electrode Polarity on Neural Activation Related to Paresthesia Coverage in Spinal Cord Stimulation Therapy. Neuromodulation: Technology at the Neural Interface. 22(3):269-279. https://doi.org/10.1111/ner.1290926927922

The effect of postural freedom to increase the neutral positions during laparoscopic surgery

[EN] Laparoscopic technique has demonstrated numerous advantages compared to open conventional surgery. Nevertheless, this procedure increases the surgeons fatigue and thus, the potential to commit errors that may harm the patient during the operation. The post-surgery pain is also augmented because the surgeons are forced to adopt non-neutral postures during the practice. This study reveals how a postural freedom element could help surgeons to improve the postural hygiene. During this study, thirteen participants with and without previous experience in laparoscopic surgery performed a test with two instruments: a prototype that implement this postural freedom concept and a conventional fixed instrument. The results obtained indicate that the postural freedom element allows the participants to maintain neutral positions during greatest part of the experiment and suggest that the implementation of an articulated element could increases the neutral positions adopted during a real laparoscopic procedure. The use of the postural freedom concept allowed to the participants to reduce the awkward positions during upper limb motions and to reduce displacements, avoiding extreme abductions that are common with the conventional fixed instruments.Pace-Bedetti, HM.; Dolz, JF.; Martínez-De-Juan, JL.; Conejero Rodilla, A. (2019). The effect of postural freedom to increase the neutral positions during laparoscopic surgery. International Journal on Interactive Design and Manufacturing (IJIDeM). 13(2):627-631. https://doi.org/10.1007/s12008-018-00527-6S62763113

What is the role of frequency on neural activation in tonic stimulation in SCS therapy? A computational study on sensoty Ab nerve fibers

[EN] The investigation of the effect of the stimulation parameters by computational modeling helps to understand the electrical response of specific neural elements in Spinal Cord Stimulation (SCS) therapy for chronic pain treatment. While the effect of the amplitude, the pulse width, and the electrode configuration on neural activation has been widely studied and is well-established in tonic stimulation, how frequency influences neural activation remains unclear. Thus, the aim of this work is to study the effect of frequency on the electrical response of sensory A beta neurons in tonic stimulation. Our approach consisted of the development of a new nerve fiber model from the combination of two previous models used in SCS modeling (the Wesselink-Holsheimer-Boom model and the Richardson-McIntyre-Grill model B). We simulate the action potential and the gates probabilities evolution of a 12.8 mu m fiber diameter at different pulse frequencies (50, 350, 600, 800, and 1000 Hz). We also simulated the firing rate of two nerve fiber diameters (5.7 and 12.8 mu m) in function of pulse frequency (from 1 to 1400 Hz) at different pulse widths (100, 300, and 500 mu s). In the range of 2-1000 Hz, the firing rate of a 12.8 mu m-diameter nerve fiber can be maximized by utilizing a 350 Hz, 300 mu s-stimulus. Frequencies above 350 Hz reduce half to one-third the firing rate, and 1000 Hz-stimulus overrides the electrical activity of the sensory nerve fiber. Small fibers (5.7 mu m-diameter) present lower firing rate values than large fibers (12.8 mu m-diameter). High values of pulse width decrease the firing rate of the nerve fibers as well as the range of frequencies that could be used to stimulate. According to the results, the frequency could have a considerable implication on the modulation of the firing rate of a nerve fiber. Thus, the frequency could play an important role to select and increase the activity of specific neural elements of the spinal cord in SCS therapy.Solanes, C.; Durá, JL.; De Andrés, J.; Saiz Rodríguez, FJ. (2021). What is the role of frequency on neural activation in tonic stimulation in SCS therapy? A computational study on sensoty Ab nerve fibers. IEEE Access. 9:107446-107461. https://doi.org/10.1109/ACCESS.2021.3099986S107446107461

Azonia derivatives of the γ-carboline system. A new class of DNA intercalators

1-Methyl-γ-carboline derivatives were transformed into the corresponding N-aminoazinium salts, which were condensed with 1,2-dicarbonyl compounds (Westphal reaction) to afford azonia derivatives with a bridgehead quaternary nitrogen atom. Some of them show DNA intercalating properties.Instituto de Qulmica Computaciona

A Surface Electromyogram Evaluation of the Postural Freedom Effects in Laparoscopic Surgery

[EN] It has been demonstrated that laparoscopic procedures benefit patients in terms of recovery time, exposure to infections and trauma. Nevertheless, it increases the number of problems for the surgeons, including the frequency and duration of awkward postures for surgeons. The repetition of these movements is considered the main cause for musculoskeletal disorders in surgeons' upper limbs. The goal of this study is to evaluate the muscular activity and muscular fatigue effect produced by both, a conventional instrument and an instrument provided with the Postural Freedom (PF) feature; which consists in a ball socket articulation that allows a variable handle-to-shaft angle, on a conventional laparoscopic pistol-grip handle. Seventeen participants were evaluated during a static simulation using both instruments. Surface electromyography was used to compare the instruments in terms of muscular activity in each target position and muscular fatigue produced in the muscles trapezius, deltoids, biceps, and flexor carpi radialis. Trapezius and deltoids were the muscles most affected. Entrance and exit targets and targets facing the participants showed the higher muscular activity values. The PF prototype reduced muscular activity in all the muscles and in the majority of the target positions showing a reduction greater than 70% of the activity required by the trapezius and deltoid muscles in comparison to the conventional tool. Muscular fatigue was produced by both instruments but it presented lower frequency values with PF prototype. The results indicated that the use of conventional instruments impacts negatively on muscular activity during laparoscopic procedures, in terms of positions adopted. The PF feature in laparoscopic instrumentation reduced the muscular activity and also decreased the signals of muscular fatigue in the muscles evaluated in comparison with the conventional tool.Pace-Bedetti, HM.; Martínez-De-Juan, JL.; Conejero Rodilla, A.; Prats-Boluda, G. (2019). A Surface Electromyogram Evaluation of the Postural Freedom Effects in Laparoscopic Surgery. IEEE. 3143-3146. https://doi.org/10.1109/EMBC.2019.88579193143314

Pyrrolodiazines. 4. Structure and chemistry of 3,4-dihydropyrrolo[1,2-a]pyrazine

The structure of 3,4-dihydropyrrolo[1,2-a]pyrazine and its N-protonated form is studied by ab initio calculations. Examples of the reactivity of this poorly studied system are presented in which it is shown that the imino moiety does not react with dienes but does undergo inter- and intramolecular 1,3-dipolar cycloadditions by reaction of azomethine ylides of this bicyclic system with suitable dipolarophiles.Ministerio de Educación y CienciaCentro de Computación de Galixia (CESGA

Evolución costera de la desembocadura del Guadalquivir en los últimos 6000 años (SW de España)

3 páginas, 2 figuras, 5 referencias.Since the last Holocene sea level rise, about 6,900 yr BP, a series of depositional littoral landforms has been generated at the outlet of the Guadalquivir river, with progradation along the predominant longshore drift (towards the east). The littoral spit systems mapped constitute fur progradation phases. The first is dated between the Flandrian maximum (6,900 yr BP) and 4,500 yr BP; the second between 4,200-3,900 yr BP and 2,700-2,600 yr BP; the third between 2,300 yr BP and 1,100 yr BP; and the fourth between 1,000 yr BP and the present. There were separations of successive erosional phases between 4,500-4,200 yr BP, 2,600-2,300 yr BP and, 1,100-1,000 yr BP. Thus, cycles of higher sedimentation are established, with a slight fall and then stability of sea level. Littoral barrier constructions dominate, with the genesis of extensive tidal flats that decrease the size of the estuaries. These sedimentary phases are interrupted by rapid rises in sea level lasting from 100 to 300 years, when the previously constructed littoral barriers are eroded. The cliffs retreat, causing migration inland of dunar constructions, with frequent overlapping layers. Marine influence within the estuaries in creases.Este trabajo ha sido subvencionado por los proyectos coordinados de la DGICYT PB91-0622-C03-0 1 y PB94-1090-C03-0l. Es una contribución al IGCP-367.Peer reviewe

Positive culture in allograft ACL-reconstruction: what to do?

The transmission of disease or infection from the donor to the recipient is always a risk with the use of allografts. We carried out a research study on the behavioural pattern of implanted allografts, which were initially stored in perfect conditions (all cultures being negative) but later presented positive cultures at the implantation stage. Because there is no information available on how to deal with this type of situation, our aim was to set guidelines on the course of action which would be required in such a case. We conducted a retrospective study of 181 patients who underwent an ACL reconstruction using BPTB allografts. All previous bone and blood cultures and tests for hepatitis B and C, syphilis and HIV were negative. An allograft sample was taken for culture in the operating theatre just before its implantation. The results of the cultures were obtained 3-5 days after the operation. We had 24 allografts with positive culture (13.25%) after the implantation with no clinical infection in any of these patients. Positive cultures could be caused by undetected contamination while harvesting, storing or during manipulation before implantation. The lack of clinical signs of infection during the follow-up of our patients may indicate that no specific treatment-other than an antibiotic protocol-would be required when facing a case of positive culture of a graft piece after its implantation

Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses

BACKGROUND AND PURPOSEExposure to an ototoxic level of an aminoglycoside can result in hearing loss. In this we study investigated the otoprotective efficacy of dexamethasone (DXM), melatonin (MLT) and tacrolimus (TCR) in gentamicin (GM)-treated animals and cultures.EXPERIMENTAL APPROACHWistar rats were divided into controls (treated with saline); exposed to GM only (GM); and three GM-exposed groups treated with either DXM, MLT or TCR. Auditory function and cochlear surface preparations were studied. In vitro studies of oxidative stress, pro-inflammatory cytokine mRNA levels, the MAPK pathway and caspase-3 activation were performed in organ of Corti explants from 3-day-old rats.KEY RESULTSDXM, MLT and TCR decreased levels of reactive oxygen species in GM-exposed explants. The mRNA levels of TNF-α, IL-1β and TNF-receptor type 1 were significantly reduced in GM + DXM and GM + MLT groups. Phospho-p38 MAPK levels decreased in GM + MLT and GM + TCR groups, while JNK phosphorylation was reduced in GM + DXM and GM + MLT groups. Caspase-3 activation decreased in GM + DXM, GM + MLT and GM + TCR groups. These results were consistent with in vivo results. Local treatment of GM-exposed rat cochleae with either DXM, MLT or TCR preserved auditory function and prevented auditory hair cell loss.CONCLUSIONS AND IMPLICATIONSIn organ of Corti explants, GM increased oxidative stress and initiated an inflammatory response that led to the activation of MAPKs and apoptosis of hair cells. The three compounds tested demonstrated otoprotective properties that could be beneficial in the treatment of ototoxicity-induced hearing loss

Current state of biology and diagnosis of clonal mast cell diseases in adults

[EN] Mastocytosis comprises a heterogeneous group of disorders characterized by the presence of clonal mast cells (MC) in organs such as skin, bone marrow (BM), and gastrointestinal tract, among other tissues. The clonal nature of the disease can be established in most adult patients by the demonstration of activating KIT mutations in their BM MC. When highly sensitive techniques capable of identifying cells present at very low frequencies in a sample are applied, BM MC from virtually all systemic mastocytosis patients display unique immunophenotypical features, particularly the aberrant expression of CD25. By contrast, large, multifocal BM MC aggregates (the only World Health Organization major criterion for systemic mastocytosis) are absent in a significant proportion of patients fulfilling at least three minor criteria for systemic mastocytosis, particularly in subjects studied at early stages of the disease with very low MC burden. Moreover, recent molecular and immunophenotypical investigations of BM MC from patients with indolent systemic mastocytosis have revealed a close association of some biological features (e.g., multilineage involvement of hematopoiesis by the KIT mutation and an immature mast cell immunophenotype) with an increased risk for disease progression. These observations support the fact that, although the current consensus diagnostic criteria for systemic mastocytosis have been a major advance for the diagnosis and classification of the disease, rationale usage of the most sensitive diagnostic techniques available nowadays is needed to improve the diagnosis, refine the classification, and reach objective prognostic stratification of adult mastocytosis