Feasibility of Full Neuromuscular Blockade During Transcranial Motor Evoked Potential Monitoring of Neurosurgical Procedures.

BACKGROUND: Transcranial motor evoked potential (TcMEP) monitoring is conventionally performed during surgical procedures without or with minimal neuromuscular blockade (NMB) because of its potential interference with signal interpretation. However, full blockade offers increased anesthetic management options and facilitates surgery. Here, the feasibility of TcMEP interpretation was assessed during full NMB in adult neurosurgical patients. METHODS: Patients undergoing cervical or lumbar decompression received a rocuronium bolus producing 95% or greater blockade by qualitative train-of-four at the ulnar nerve. TcMEPs were recorded in bilateral thenar-hypothenar and abductor hallucis muscles. Adequacy of response for reliable signal interpretation was determined on the basis of repeatability and clarity, assessed by coefficient of variation and signal-to-noise ratio, respectively. RESULTS: All patients had at least 3 of 4 measurable TcMEP limb responses present during full NMB, and 70.8% of patients had measurable responses in all 4 limbs. In total, 82.2% of thenar-hypothenar responses and 62.8% of abductor hallucis responses were robust enough for reliable signal interpretation on the basis of clarity. In addition, 97.8% of thenar-hypothenar responses and 79.1% of abductor hallucis responses met the criteria for reliable signal interpretation on the basis of consistency. Patient demographics, medical comorbidities, and preoperative weakness were not predictive of absent responses during full NMB. CONCLUSIONS: TcMEP interpretation may be feasible under greater levels of NMB than previously considered, allowing for monitoring with greater degrees of muscle relaxation. Consideration for monitoring TcMEP during full NMB should be made on a case-by-case basis, and baseline responses without blockade may predict which patients will have adequate responses for interpretation.

Evaporation kinetics of a polydisperse ensemble of drops.

A mathematical model of the evaporation of a polydisperse ensemble of drops, with allowance for a nonlinear 'diffusion' term in the kinetic equation for the population density distribution function, is developed. The model describes the interaction of a gas phase with vaporizing drops: it has great potential for application in condensed matter physics, thermophysics and engineering devices (e.g. spray drying, cooling, power engineering). The kinetics of heat transfer between phases is theoretically studied. An analytical solution to the integro-differential equations of the process of droplet evaporation is found in a parametric form. Analytical solutions in the presence and absence of the 'diffusion' term are compared. It is shown that the fluctuations in particle evaporation rates ('diffusion' term in the Fokker-Planck equation) play a decisive role in the evolutionary behaviour of a polydisperse ensemble of vaporizing liquid drops. This article is part of the theme issue 'Transport phenomena in complex systems (part 1)'.

Dissolution of polydisperse ensembles of crystals in channels with a forced flow.

A non-stationary integro-differential model describing the dissolution of polydisperse ensembles of crystals in channels filled with flowing liquid is analysed. The particle-size distribution function, the particle flux through an arbitrary cross-section of the channel, the particle concentration profile, as well as the disappearance intensity of particles are found analytically. It is shown that a nonlinear behaviour of solutions is completely defined by the source term of particles introduced into the channel. In particular, the model approximately describes the processes of dissolution and transport of drug microcrystals to the target sites in a living organism, taking into account complex dissolution kinetics of drug particles. This article is part of the theme issue 'Patterns in soft and biological matters'.

Phase transformations in metastable liquids combined with polymerization.

This paper is concerned with the theory of nucleation and growth of crystals in a metastable polymer melt with allowance for the polymerization of a monomer. A mathematical model consisting of the heat balance equation, equations governing the particle-radius distribution function and the polymerization degree is formulated. The exact steady-state analytical solutions are found. In the case of unsteady-state crystallization with polymerization, the particle-size distribution function is determined analytically for different space-time regions by means of the Laplace transform. Two functional integro-differential equations governing the dimensionless temperature and polymerization degree are deduced. These equations are solved by means of the saddle-point technique for the evaluation of a Laplace-type integral. The time-dependent distribution function, temperature and polymerization degree at different polymerization rates and nucleation kinetics are derived with allowance for the main contribution to the Laplace-type integral. In addition, the general analytical solution by means of the saddle-point technique and an example showing how to construct the analytical solutions in particular cases are given in the appendices. The analytical method developed in the present paper can be used to describe the similar phase transition phenomena in the presence of chemical reactions. This article is part of the theme issue 'Heterogeneous materials: metastable and non-ergodic internal structures'.

DNA sequence-specific dimeric bisbenzimidazoles DBP(n) and DBPA(n) as inhibitors of H-NS silencing in bacterial cells.

DNA sequence-specific fluorescent dimeric bisbenzimidazoles DBP(n) and DBPA(n), noncovalently interacting with A-T pairs in the minor groove of double-stranded DNA were used for studying and monitoring the expression of histone-like H-NS-dependent promoters. Histone-like H-NS selectively binds to AT-rich segments of DNA and silences a large number of genes in bacterial chromosomes. The H-NS-dependent promoters of Quorum Sensing (QS)-regulated lux operons of the marine bacteria mesophilic Aliivibrio fischeri, psychrophilic Aliivibrio logei were used. Escherichia coli lux biosensors were constructed by cloning fragments bearing QS-regulated promoters into the vector, thereby placing each fragment upstream of the promoterless Photorhabdus luminescens luxCDABE genes. It was shown that the dimeric bisbenzimidazoles DBP(n) and DBPA(n) counteract the H-NS silencing activity. Thus, the presence of DBP(n) or DBPA(n) in the medium leads to an approximately 10-100-fold increase in the level of transcription of QS promoters in E. coli hns+. The largest decrease in the level of H-NS repression was observed using ligands containing a linker with a length of ca. 18Å, such as DBP(2) and DBPA(2). Ligands containing linkers with n=1 and 3 are an order of magnitude less active; ligands with n=4 are inactive. DBPA(2) exhibits activity starting with a concentration of 0.5µM; the minimum concentration of DBP(2) is 5-7 times higher. It is suggested that A-T pairs located at five nucleotide pair intervals, which correspond to the linker length in highly active ligands with n=2, play a key role in the structure of H-NS-binding sites in QS-regulated promoters.

Symmetric dimeric bisbenzimidazoles DBP(n) reduce methylation of RARB and PTEN while significantly increase methylation of rRNA genes in MCF-7 cancer cells.

BACKGROUND: Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n) are able to block DNA methyltransferase activities. It was also found that DBP(n) produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome. PRINCIPAL FINDINGS: It is shown that DBP(n) are able to penetrate the cellular membranes and accumulate in breast carcinoma cell MCF-7, mainly in the mitochondria and in the nucleus, excluding the nucleolus. The DBP(n) are non-toxic to the cells and have a weak overall demethylation effect on genomic DNA. DBP(n) demethylate the promoter regions of the tumor suppressor genes PTEN and RARB. DBP(n) promotes expression of the genes RARB, PTEN, CDKN2A, RUNX3, Apaf-1 and APC "silent" in the MCF-7 because of the hypermethylation of their promoter regions. Simultaneously with the demethylation of the DNA in the nucleus a significant increase in the methylation level of rRNA genes in the nucleolus was detected. Increased rDNA methylation correlated with a reduction of the rRNA amount in the cells by 20-30%. It is assumed that during DNA methyltransferase activity inhibition by the DBP(n) in the nucleus, the enzyme is sequestered in the nucleolus and provides additional methylation of the rDNA that are not shielded by DBP(n). CONCLUSIONS/SIGNIFICANCE: It is concluded that DBP (n) are able to accumulate in the nucleus (excluding the nucleolus area) and in the mitochondria of cancer cells, reducing mitochondrial potential. The DBP (n) induce the demethylation of a cancer cell's genome, including the demethylation of the promoters of tumor suppressor genes. DBP (n) significantly increase the methylation of ribosomal RNA genes in the nucleoli. Therefore the further study of these compounds is needed; it could lead to the creation of new anticancer agents.

Analytical solutions of mushy layer equations describing directional solidification in the presence of nucleation.

The processes of particle nucleation and their evolution in a moving metastable layer of phase transition (supercooled liquid or supersaturated solution) are studied analytically. The transient integro-differential model for the density distribution function and metastability level is solved for the kinetic and diffusionally controlled regimes of crystal growth. The Weber-Volmer-Frenkel-Zel'dovich and Meirs mechanisms for nucleation kinetics are used. We demonstrate that the phase transition boundary lying between the mushy and pure liquid layers evolves with time according to the following power dynamic law: [Formula: see text], where Z1(t)=ßt7/2 and Z1(t)=ßt2 in cases of kinetic and diffusionally controlled scenarios. The growth rate parameters α, ß and ε are determined analytically. We show that the phase transition interface in the presence of crystal nucleation and evolution propagates slower than in the absence of their nucleation.This article is part of the theme issue 'From atomistic interfaces to dendritic patterns'.

Recurrence of Cerebral Arteriovenous Malformations Following Resection in Adults: Does Preoperative Embolization Increase the Risk?

BACKGROUND: Complete surgical resection of arteriovenous malformations (AVMs), documented by postoperative angiography, is generally felt to represent cure, obviating the need for long-term follow-up imaging. Although AVM recurrence has been reported in the pediatric population, this phenomenon has only rarely been documented in adults. Recurrence after treatment solely with embolization, however, has been reported more frequently. Thus, patients undergoing multimodal therapy with surgery following preoperative embolization may also be at higher risk for recurrence. OBJECTIVE: To determine if preoperative embolization contributes to recurrences of AVMs after complete surgical resection. METHODS: A retrospective study of patients undergoing AVM resection was performed. Those with complete surgical AVM resection, confirmed by negative early postoperative cerebral angiography and with available follow-up angiographic imaging >6 months postoperatively were included. RESULTS: Two hundred three patients underwent AVM resection between 1995 and 2012. Seventy-two patients met eligibility criteria. There were 3 recurrences (4%). Deep venous drainage and diffuse type of AVM nidus were significantly associated with recurrence. Although preoperative embolization did not reach statistical significance as an independent risk factor, radiographic data supported its role in every case, with the site of recurrence correlating with deep regions of nidus previously obliterated by embolization. CONCLUSION: AVM recurrences in the adult population may have a multifactorial origin. Although deep venous drainage and diffuse nidus are clearly risk factors, preoperative embolization may also be a contributing factor with the potential for recurrence of unresected but embolized portions of the AVM. Follow-up angiography at 1 to 3 years appears to be warranted.

DNA specific fluorescent symmetric dimeric bisbenzimidazoles DBP(n): the synthesis, spectral properties, and biological activity.

A series of new fluorescent symmetric dimeric bisbenzimidazoles DBP(n) bearing bisbenzimidazole fragments joined by oligomethylene linkers with a central 1,4-piperazine residue were synthesized. The complex formation of DBP(n) in the DNA minor groove was demonstrated. The DBP(n) at micromolar concentrations inhibit in vitro eukaryotic DNA topoisomerase I and prokaryotic DNA methyltransferase (MTase) M.SssI. The DBP(n) were soluble well in aqueous solutions and could penetrate cell and nuclear membranes and stain DNA in live cells. The DBP(n) displayed a moderate effect on the reactivation of gene expression.

Bisbenzimidazole derivatives as potent inhibitors of the trypsin-like sites of the immunoproteasome core particle.

In this study, a monomeric (MB) and a dimeric (DB) bisbenzimidazoles were identified as novel proteasome inhibitors of the trypsin-like activity located on ß2c sites of the constitutive 20S proteasome (IC50 values at 2-4 µM range). Remarkably, they were further shown to be 100- and 200-fold more potent inhibitors of the immunoproteasome trypsin-like activity (ß2i sites, IC50=24 nM) than of the homologous constitutive activity. Molecular models of inhibitor/enzyme complexes in the two types of trypsin-like sites and corresponding computed binding energy values corroborated kinetic data. Different binding modes were suggested for MB and DB to the ß2c and ß2i trypsic sites. Each pointed to better contacts of the ligand inside the ß2i active site than for ß2c site. MB and DB represent the first selective inhibitors of the immunoproteasome trypsin-like activity described to date and can be considered as prototypes for inhibiting this activity.

Inhibition of the helicase activity of the HCV NS3 protein by symmetrical dimeric bis-benzimidazoles.

Dimeric bis-benzimidazoles (DBn) are the compounds specifically binding to A-T enriched sequences in the DNA minor groove. Due to this property they can inhibit DNA-dependent enzymes. We show that inhibition of the helicase activity of HCV NS3 protein by DBn was due to a novel mechanism, which involved direct binding of the ligands to the enzyme. The binding potency and inhibition efficacy depended on the length of the linker between the benzimidazole fragments. The most effective inhibitor DB11 partially prevented activation of NTPase activity of NS3 by poly(U) and increased affinity of the enzyme to the helicase substrate DNA.

Confirmation studies of Soviet research on immunological effects of microwaves: Russian immunology results.

This paper presents the results of a replication study performed to investigate earlier Soviet studies conducted between 1974 and 1991 that showed immunological and reproductive effects of long-term low-level exposure of rats to radiofrequency (RF) electromagnetic fields. The early studies were used, in part, for developing exposure standards for the USSR population and thus it was necessary to confirm the Russian findings. In the present study, the conditions of RF exposure were made as similar as possible to those in the earlier experiments: Wistar rats were exposed in the far field to 2450 MHz continuous wave RF fields with an incident power density in the cages of 5 W/m² for 7 h/day, 5 days/week for a total of 30 days, resulting in a whole-body SAR of 0.16 W/kg. Effects of the exposure on immunological parameters in the brain and liver of rats were evaluated using the complement fixation test (CFT), as in the original studies, and an additional test, the more modern ELISA test. Our results, using CFT and ELISA, partly confirmed the findings of the early studies and indicated possible effects from non-thermal RF exposure on autoimmune processes. The RF exposure resulted in minor increases in formation of antibodies in brain tissue extract and the exposure did not appear to be pathological. In addition, a study was conducted to replicate a previous Soviet study on effects from the injection of blood serum from RF-exposed rats on pregnancy and foetal and offspring development of rats, using a similar animal model and protocol. Our results showed the same general trends as the earlier study, suggesting possible adverse effects of the blood serum from exposed rats on pregnancy and foetal development of intact rats, however, application of these results in developing exposure standards is limited.

Lumbar fusion leads to increases in angular motion and stress across sacroiliac joint: a finite element study.

STUDY DESIGN: The assessment of sacrum angular motions and stress across sacroiliac joint (SIJ) articular surfaces using finite element lumbar spine-pelvis model and simulated posterior fusion surgical procedures. OBJECTIVE: To quantify the increase in sacrum angular motions and stress across SIJ as a function of fused lumbar spine using finite element lumbar spine-pelvis model. SUMMARY OF BACKGROUND DATA: A review of the literature suggests that for 20% to 30% of spine surgery patients, failed back surgery syndrome as a possible complication. The SIJ might be a contributing factor in failed back surgery syndrome in 29% to 40% of cases. The exact pathomechanism which leads to SIJ pain generation is not well understood. We hypothesized that lumbar spine fusion leads to increased motion or stresses at the SIJ; this alone could be a trigger of the pain syndrome. METHODS: A finite element model of the lumbar spine-pelvis was used to simulate the posterior fusion at L4-L5, L4-S1, and L5-S1 levels. The magnitude of the sacrum angular motion and average of stresses across SIJ articular surfaces were compared with intact model in flexion, extension, lateral bending, and axial rotation motions. RESULTS: The computed sacrum angular motions in intact spine, after L4-L5, L5-S1, and L4-S1 fusion gradually increased with maximum value in L4-S1 fusion model. Also, the average stress on SIJ articular surfaces progressively increased from minimum in L4-L5 to maximum in L4-S1 fusion models. CONCLUSION: The fusion at the lumbar spine level increased motion and stresses at the SIJ. This could be a probable reason for low back pain in patients after lumbar spine fusion procedures.

Ion sources with arc-discharge plasma box driven by directly heated LaB(6) electron emitter or cold cathode.

In the Budker Institute, Novosibirsk, an ion source with arc-discharge plasma box has been developed in the recent years for application in thermonuclear devices for plasma diagnostics. Several modifications of the ion source were provided with extracted current ranging from 1 to 7 A and pulse duration of up to 4 s. Initially, the arc-discharge plasma box with cold cathode was used, with which pulse duration is limited to 2 s by the cathode overheating and sputtering in local arc spots. Recently, a directly heated LaB(6) electron emitter was employed instead, which has extended lifetime compared to the cold cathode. In the paper, characteristics of the beam produced with both arrangements of the plasma box are presented.

The effect of removing the lateral part of the pars interarticularis on stress distribution at the neural arch in lumbar foraminal microdecompression at L3-L4 and L4-L5: anatomic and finite element investigations.

STUDY DESIGN: The assessment of L3 and L4 pars interarticularis thickness and finite element analysis of stress distribution across L3 and L4 pars interarticularis. OBJECTIVE: To quantify the morphology of the region of the L3 and L4 pars interarticularis and to assess the stress increase as a function of access size using the finite element lumbar spine model. SUMMARY OF BACKGROUND DATA: Inadequate decompression and traction of the nerve structures are several causes of the unsatisfactory outcomes in patients after foraminal stenosis decompression and far lateral disc herniation removal by extraforaminal exposure. Enlarging the access of the foraminal exposure by the removal of the lateral aspect of the pars interarticularis may be able to diminish the inadequate decompression and traction of the nerve structures; however, it may lead to increase stress and fracture of the neural arch. METHODS: We used 15 human cadaver L3 and L4 lumbar vertebrae for measuring the thickness of the pars interarticularis. The ventral and dorsal surfaces were subdivided into 4 equal parts, and the thickness of each part was measured using a digital caliper. An experimentally validated 3-dimensional nonlinear finite element model of the intact L3-S1 segment was used to simulate the lateral removal of one fourth and one half of the L3 and L4 pars interarticularis. RESULTS: The mean thicknesses of the pars interarticularis showed a gradual increase toward the lateral edge. Finite element model analyses predicted stresses increased to 35% and 40% after removal of one half of the lateral part of the L3 and L4 pars interarticularis, respectively, and were much closer to the intact spine after removal of one fourth of the lateral part of the pars interarticularis. CONCLUSION: The removal of one fourth of the lateral aspect of the pars interarticularis has minimal influence on the stresses in the remaining L3 and L4 neural arches. The lateral half of the pars has the largest thickness, and its removal leads to considerable stress increases.