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

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

Treatment of Neuropathic Pain in Brachial Plexus Injuries

Brachial plexus injuries are commonly followed by chronic pain, mostly with neuropathic characteristics. This is due to peripheral nerve lesions, particularly nerve root avulsions, as well as upper limb amputations, and complex regional pain syndrome (CRPS). The differential diagnosis between CRPS and neuropathic pain is essential as the treatment is different for each of them. Medical treatments are the first step, but for refractory cases there are two main types of surgical alternatives: ablative techniques and neuromodulation. The first group involves destruction of the posterior horn deafferented neurons and usually provides a better pain control but has a 10% complication rate. The second group provides pain control with function preservation but with limited effectiveness. Each case has to be thoroughly evaluated to apply the treatment modality best suited for it

Structure of the receptor-binding carboxy-terminal domain of the bacteriophage T5 L-shaped tail fibre with and without its intra-molecular chaperone

Bacteriophage T5, a Siphovirus belonging to the order Caudovirales, has a flexible, three-fold symmetric tail, to which three L-shaped fibres are attached. These fibres recognize oligo-mannose units on the bacterial cell surface prior to infection and are composed of homotrimers of the pb1 protein. Pb1 has 1396 amino acids, of which the carboxy-terminal 133 residues form a trimeric intra-molecular chaperone that is auto-proteolyzed after correct folding. The structure of a trimer of residues 970–1263 was determined by single anomalous dispersion phasing using incorporated selenomethionine residues and refined at 2.3 Å resolution using crystals grown from native, methionine-containing, protein. The protein inhibits phage infection by competition. The phage-distal receptor-binding domain resembles a bullet, with the walls formed by partially intertwined beta-sheets, conferring stability to the structure. The fold of the domain is novel and the topology unique to the pb1 structure. A site-directed mutant (Ser1264 to Ala), in which auto-proteolysis is impeded, was also produced, crystallized and its 2.5 Å structure solved by molecular replacement. The additional chaperone domain (residues 1263–1396) consists of a central trimeric alpha-helical coiled-coil flanked by a mixed alpha-beta domain. Three long beta-hairpin tentacles, one from each chaperone monomer, extend into long curved grooves of the bullet-shaped domain. The chaperone-containing mutant did not inhibit infection by competition.This research was sponsored by grants BFU2011-24843, BIO2011-14756-E, BFU2014-53425P (Mark J. van Raaij), and BFU2014-55475R (José R. Castón) and the BioFiViNet network (FIS2011-16090-E) from the Spanish Ministry of Economy and Competitiveness, grant S2013/MIT-2807 (José R. Castón) from the Comunidad Autónoma de Madrid and a joint networking grant from CSIC (2011FR0016; Mark J. van Raaij) and CNRS (2011EDC25326; Pascale Boulanger). Carmela Garcia-Doval was the recipient of a pre-doctoral FPU fellowship from the Spanish Ministry of Education, Culture and Sports and José M. Otero of a post-doctoral Plan I2C fellowship from the Xunta de Galicia. The research leading to these results has also received funding from the European Community’s Seventh Framework Programme (FP7/2007–2013) under BioStruct-X (grant agreement number 283570). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer Reviewe

Colored microbial coatings in show caves from the galapagos islands (Ecuador): first microbiological approach

The Galapagos Islands (Ecuador) have a unique ecosystem on Earth due to their outstanding biodiversity and geological features. This also extends to their subterranean heritage, such as volcanic caves, with plenty of secondary mineral deposits, including coralloid-type speleothems and moonmilk deposits. In this study, the bacterial communities associated with speleothems from two lava tubes of Santa Cruz Island were investigated. Field emission scanning electron microscopy (FESEM) was carried out for the morphological characterization and detection of microbial features associated with moonmilk and coralloid speleothems from Bellavista and Royal Palm Caves. Microbial cells, especially filamentous bacteria in close association with extracellular polymeric substances (EPS), were abundant in both types of speleothems. Furthermore, reticulated filaments and Actinobacteria-like cells were observed by FESEM. The analysis of 16S rDNA revealed the presence of different bacterial phylotypes, many of them associated with the carbon, nitrogen, iron and sulfur cycles, and some others with pollutants. This study gives insights into subsurface microbial diversity of the Galapagos Islands and further shows the interest of the conservation of these subterranean geoheritage sites used as show caves.Ministerio del Ambiente de Ecuador (Parque Nacional Galápagos)-PC-65-14Ministerio de Economía y Competitividad de España (MINECO) y el Fondo Europeo de Desarrollo Regional de la Unión Europea (FEDER)-CGL2016-75590-PPortuguese Foundation for Science and Technology. Fundação para a Ciência e a Tecnologia (FCT)-UID/Multi/04449/2019 HERCULES/U

Monitoring of the flexor-extensor musculature of the knee in high-performance female volleyball players

[ES] El propósito del estudio fue describir, a través de TMG, los cambios producidos en las características mecánicas de la musculatura responsable de la flexo extensión de la articulación de la rodilla: antes y después de un periodo de entrenamiento, en jugadoras de voleibol de alto nivel competitivo. Así, se controlaron el Vasto Medial (VM), el Recto Femoral (RF), el Vasto Lateral (VL), el Semitendinoso (ST) y el Bíceps Femoral (BF). Además, se presentan los resultados obtenidos en una batería de saltos realizados sobre una plataforma de contacto durante este mismo periodo de entrenamiento: Squat Jump (SJ), Countermovement Jump (CMJ), Salto de Remate (REM) y Salto de Bloqueo (BLQ). Se evaluaron dieciséis jugadoras (edad 20,3 ± 1,7 años; peso corporal: 67,75 ± 9,13 kg.; altura: 178,2 ± 7,1 cm.; IMC: 21,41 ± 1,75 kg/m 2) pertenecientes a 2 equipos de Superliga femenina. Los resultados obtenidos muestran claras diferencias en los valores pre-post de todos los parámetros evaluados: Altura de Salto, Velocidad de respuesta normalizada (Vrn), Deformación Máxima radial del músculo (Dm), Tiempo de Activación (Td), Tiempo de Mantenimiento de la contracción (Ts), Tiempo de relajación (Tr); siendo estadísticamente significativos los valores de Vrn del VL (p<0,001; ES=1,11); y encontrando una tendencia estadística en Vrn del RF (p=0,117; ES=0,69). En este sentido, podemos concluir que el entrenamiento produce adaptaciones en la musculatura implicada en la flexo-extensión de la rodilla de jugadoras de voleibol de alto nivel competitivo, y que dichos cambios pueden monitorizarse a través del estudio de la modificación de las características mecánicas musculares evaluadas mediante Tensiomiografía.SIConsejo Superior de Deportes y La Universidad Europea de Madri

Impact of renal retransplantation on graft and recipient survival

The aim of this study was to evaluate the influence of retransplantation in graft and recipient survival. METHODS: We carried out a retrospective study in 419 renal transplants and studied the influence of retransplantation in graft and patient survival. A homogeneity study was performed between the two groups with a Student`s T and a chi-square tests. Graft survival analysis was performed with Kaplan-Meyer and log rank tests. RESULTS: Of 419 transplants, 370 (88.3%) were first transplantations, 45 (10.7%) second transplantations and 4(1%) third ones. Mean follow-up of the whole group was 72.5 months (+/-54.1 SD). There were no differences in follow-up between groups (Mean Follow-up 73.1 months +/-54.4 SD in first transplantations vs. 61.6 months +/-51.2 SD in repeat transplantation. p >0.05). The actuarial graft survival showed no differences between patients with first transplantation and those with a repeat one. [3 and 5 year SV of 89% (95% CI: 87-91%) and 84%(95% CI: 82-86%) Vs 88% (95% CI; 83-93%) and 85% (95% CI:i; 80-90%) respectively]. After adjusting for all the heterogeneity variables we still did not find differences on graft survival. The actuarial recipient survival showed no differences between patients with first transplantation and those with a repeat one. [3 and 5 year SV of 98% and 96% Vs.97%]. CONCLUSIONS: There are no differences of graft and recipient survival between patients with a first transplantation and those with a repeat one

Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study

Objective: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). Methods: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mix- ture modeling was used to define a cut-off for KFLC and LFLC indexes. Results: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI=4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. Conclusion: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS