Central nervous system microstimulation: Towards selective micro-neuromodulation

Electrical stimulation technologies capable of modulating neural activity are well established for neuroscientific research and neurotherapeutics. Recent micro-neuromodulation experimental results continue to explain neural processing complexity and suggest the potential for assistive technologies capable of restoring or repairing of basic function. Nonetheless, performance is dependent upon the specificity of the stimulation. Increasingly specific stimulation is hypothesized to be achieved by progressively smaller interfaces. Miniaturization is a current focus of neural implants due to improvements in mitigation of the body's foreign body response. It is likely that these exciting technologies will offer the promise to provide large-scale micro-neuromodulation in the future. Here, we highlight recent successes of assistive technologies through bidirectional neuroprostheses currently being used to repair or restore basic brain functionality. Furthermore, we introduce recent neuromodulation technologies that might improve the effectiveness of these neuroprosthetic interfaces by increasing their chronic stability and microstimulation specificity. We suggest a vision where the natural progression of innovative technologies and scientific knowledge enables the ability to selectively micro-neuromodulate every neuron in the brain

Technique of Rutkow and Robbins (plug and patch) to the reparation of inguinals hernias

Objetivo: Caracterizar la reparación de las hernias inguinales según la técnica de Rutkow y Robbins (tapón y parche) con malla de polipropileno. Material y Métodos: Se realizó un estudio descriptivo donde se evaluaron 102 pacientes de la Consulta de Cirugía General, del Hospital Dr. Manuel Noriega Trigo, San Francisco, Venezuela con diagnóstico de hernia inguinal primaria, en el lapso de enero 2002 a 30 de septiembre 2005. Se practicaron 124 hernioplastias porque 11 pacientes presentaban hernias bilaterales. Se valoró sexo, edad, tipo de hernia, tiempo quirúrgico, dolor postoperatorio, período de estancia hospitalaria, reincorporación al trabajo habitual y complicaciones. Resultados: Del total de pacientes, 91 (89.2%) eran del sexo masculino y 11 (10.8%) del femenino. El promedio de edad fue 42.7±18.29, con un rango que oscilaba entre 12 y 82 años, el grupo etario más frecuente fue de 21 a 30 años (23.5%). En el sexo masculino predominó la hernia inguinal indirecta con 47 casos de los cuales 25.5% eran derechas y 20.6% izquierdas, en el sexo femenino prevaleció la hernia directa con 4 casos (3.9%). El tiempo quirúrgico tuvo un promedio de 32.18±6.42 minutos. El dolor postoperatorio se informó como molestia (33.3%) o leve (39.2%) en la mayoría de los casos, moderado en 8.8% y en ningún caso se supo de dolor severo. La estancia hospitalaria fue 23.41±3.8 horas, con cifras entre 3 y 40 horas; el reintegro al trabajo promedió 21.56±6.5 días (entre 10 y 40). Las complicaciones post-operatorias se presentaron en 6.9% de los pacientes: infección de la herida, 1%; hematoma, 1%; seromas, 2%; 1% neuralgia inguinal, 1%; y retención urinaria, 2%. Conclusión: Técnica rápida de ejecutar, poca morbilidad postoperatoria, corta estancia, pronto reintegro laboral y escasas complicaciones, por lo que demostró ser segura para la reparación de las hernias inguinales. Objective: To describe the repair process of inguinal hernias according to the Rutkow and Robbins technique (plug and patch) and polypropylene mesh. Methods: A descriptive study was performed on 102 patients attending to the Surgery Clinic at Hospital Dr. Manuel Noriega Trigo, San Francisco, Venezuela. Patients had a diagnosis of primary inguinal hernia during the period of January 2002 to September, 2005. 124 hernioplasties were practiced, 11 patients received surgery for bilateral hernias. Variables in this study included: sex, age, hernia type, surgical time, postoperation pain, period of hospital staying, time for returning to daily activities, and complications. Results: Ninety one males (89.2%) and eleven females (10.8%) were included in this study. Average age was of 42.7±18.29 years (Range, 12-82) and the more frequent age group lies between 21 to 30 years (23.5%). Inguinal indirect hernia was more common on males (n=47, 25.5% right side. 20.6% left side). The direct inguinal hernia was present on 4 females (3.9%). The duration of the surgical procedure was 32.18±6.42 minutes. Postoperative pain was reported as discomfort (33.3%), mild (39.2%), moderate (8.8%), and no patients reported severe pain. Duration of hospital stay was 23.41±3.8 hours (Range, 3 to 40 hours), time for returning to daily activities was 21.56±6.5 days (Range, 10 to 40). The postoperative complications presented on 6.9% of the patients: 1% wound infection, 1% hematoma, 2% seromas, 1% inguinal neuralgia and 2% urinary retention. Conclusion: This is a quick technique associated with little postoperative morbidity, short hospital stay, short time for returning to daily activities and rare complications. This technique proves to be safe for the repair of inguinal hernias

Modeling elastic and photoassisted transport in organic molecular wires: length dependence and current-voltage characteristics

Using a pi-orbital tight-binding model, we study the elastic and photoassisted transport properties of metal-molecule-metal junctions based on oligophenylenes of varying lengths. The effect of monochromatic light is modeled with an ac voltage over the contact. We first show how the low-bias transmission function can be obtained analytically, using methods previously employed for simpler chain models. In particular, the decay coefficient of the off-resonant transmission is extracted by considering both a finite-length chain and infinitely extended polyphenylene. Based on these analytical results, we discuss the length-dependence of the linear-response conductance, the thermopower, and the light-induced enhancement of the conductance in the limit of weak intensity and low frequency. In general the conductance-enhancement is calculated numerically as a function of the light frequency. Finally, we compute the current-voltage characteristics at finite dc voltages, and show that in the low-voltage regime, the effect of low-frequency light is to induce current steps with a voltage separation determined by twice the frequency. These effects are more pronounced for longer molecules. We study two different profiles for the dc and ac voltages, and it is found that the results are robust with respect to such variations. Although we concentrate here on the specific model of oligophenylenes, the results should be qualitatively similar for many other organic molecules with a large enough electronic gap.Comment: 15 pages, 11 figures, minor corrections to old versio

A review on golimumab in the treatment of psoriatic arthritis

Psoriatic arthritis (PsA) causes inflammation in and around the joints and usually affects people who already have psoriasis. However, some patients develop the joint problems before the psoriasis. Currently, there are five anti-TNF-α agents licensed for use in patients with PsA: adalimumab, certolizumab pegol, etanercept, golimumab and infliximab. Golimumab, a human monoclonal antibody, has been approved by the US FDA for the treatment of PsA and is targeted against the pro-inflammatory molecule TNF-α. The Phase III GO-REVEAL study confirmed this drug was well tolerated and showed significant improvement in disease activity compared with placebo

Organic phase separation opens up new opportunities to interrogate the RNA-binding proteome.

Protein-RNA interactions regulate all aspects of RNA metabolism and are crucial to the function of catalytic ribonucleoproteins. Until recently, the available technologies to capture RNA-bound proteins have been biased toward poly(A) RNA-binding proteins (RBPs) or involve molecular labeling, limiting their application. With the advent of organic-aqueous phase separation-based methods, we now have technologies that efficiently enrich the complete suite of RBPs and enable quantification of RBP dynamics. These flexible approaches to study RBPs and their bound RNA open up new research avenues for systems-level interrogation of protein-RNA interactions

NMR structure of μ-conotoxin GIIIC : leucine 18 induces local repacking of the N-terminus resulting in reduced NaV channel potency

mu-Conotoxins are potent and highly specific peptide blockers of voltage-gated sodium channels. In this study, the solution structure of mu-conotoxin GIIIC was determined using 2D NMR spectroscopy and simulated annealing calculations. Despite high sequence similarity, GIIIC adopts a three-dimensional structure that differs from the previously observed conformation of mu-conotoxins GIIIA and GIIIB due to the presence of a bulky, non-polar leucine residue at position 18. The side chain of L18 is oriented towards the core of the molecule and consequently the N-terminus is re-modeled and located closer to L18. The functional characterization of GIIIC defines it as a canonical mu-conotoxin that displays substantial selectivity towards skeletal muscle sodium channels (Na-V), albeit with similar to 2.5-fold lower potency than GIIIA. GIIIC exhibited a lower potency of inhibition of Na(V)1.4 channels, but the same Na-V selectivity profile when compared to GIIIA. These observations suggest that single amino acid differences that significantly affect the structure of the peptide do in fact alter its functional properties. Our work highlights the importance of structural factors, beyond the disulfide pattern and electrostatic interactions, in the understanding of the functional properties of bioactive peptides. The latter thus needs to be considered when designing analogues for further applications

Trypanosoma (Herpetosoma) rangeli Tejera, 1920: intracellular amastigote stages of reproduction in white mice

The method, site, and stage of multiplication of Trypanosoma (Herpetosoma) rangeli Tejera, 1920 has not hitherto been known. "We have now observed many intracellular nests or pseudocysts, containing amastigotes and trypomastigotes of this parasite in the heart, liver, and spleen of suckling (5.0 g) male white mice (NMRI strain) inoculated i.p. with 9 x 10(4) metatrypomastigotes/g body weight from a 12-day-old culture of the "Dog-82" strain of T. rangeli. At the peak of parasitemia (1.9 x 10(6) trypomastigotes/ml blood, 3 days post-inoculation) various tissues were taken for sectioning and staining. The heart was most intensely parasitized. The amastigotes were rounded or ellipsoidal, with a rounded nucleus and the kinetoplast in the form of a straight or curved bar; the average maximum diameter of 50 measured amastigotes was 4.2 p. Binary fission was seen in the nucleus and kinetoplast of some amastigotes; no blood trypomastigotes were seen in division. The above characteristics, as well as the location of the pseudocysts in the tissues, are similar to T. cruzi. Comparison of these results with those reported for other Herpetosoma suggest study of the taxonomic position of T. rangeli