Nanosecond pulsed electric fields induce the integrated stress response via reactive oxygen species-mediated heme-regulated inhibitor (HRI) activation.

The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS.

Fogo em campo cirúrgico - Medidas preventivas para cirurgia palpebral segura / Operating room fire prevention - preventive measures for safe eyelid surgery

Resumo Fogo em campo cirúrgico durante cirurgia palpebral é uma complicação intra-operatória que é dramática tanto para o paciente quanto para a equipe médica. Relatamos um caso de acidente cirúrgico durante cirurgia palpebral onde o paciente sofreu queimadura de supercílio. Houve interação entre o oxigênio usado para sedação (máscara aberta) e uma fonte de ignição representada pelo cautério monopolar. Embora o paciente tenha apresentado boa evolução clínica com recuperação total da lesão cutânea, este caso é um alerta para se evitar tais tipo de ocorrência. Ressaltamos neste trabalho quais as condições implicadas e o modo de prevenção.

Abstract Fire in the surgical field during eyelid surgery is an intra-operative complication that is dramatic for both the patient and the medical staff. It's being reported a case of surgical accident during eyelid surgery where the patient suffered a brow burn. There was interaction between the oxygen used for sedation (open mask) and a source of ignition represented by monopolar cautery. Although the patient presented good clinical evolution with complete recovery of the cutaneous lesion, this case is an alert to avoid such type of occurrence. This work highlights the conditions involved and the way of prevention.

Electric shock-induced cardiac injuries requiring surgical intervention: Case series and a brief review.

BACKGROUND: Electric shock-induced cardiac injuries, such as myocardial infarction, thrombosis, and dissection, are rare. Few cases have been previously reported. The right coronary artery is most often affected because of its proximity to the chest wall. AIMS: To study the extend of electrical injuries on cardiac tissues and its surgical management. MATERIALS AND METHODS: We conducted a retrospective study on our patients in the last five years, looking for cardiac electrical injuries treated surgically in our department, we identified three cases. RESULT: Our three-case series, reported herein, showed that multiple cardiac tissues are susceptible to electrical injuries, specifically the left coronary artery, inferior vena cava, and right ventricular free wall. In our series, the first patient was a 32-year-old man with triple vessel thrombosis and dissection who survived the electric shock. The second patient was a 23-year-old man who had an inferior vena cava burn and bruising; his heart was used for transplantation. After the transplant, the recipient had a left coronary artery dissection and underwent coronary artery bypass grafting. The third patient was a 30-year-old man (potential heart donor) who had a hematoma of the right ventricular free wall, possible coronary artery dissection, inferior vena cava bruising, and tissue damage. His heart was not used for transplant because of quality concerns. CONCLUSION: We recommend that any person who sustains high voltage (500 V or more) electric shock should be evaluated carefully in the emergency department, including with echocardiography and cardiac catheterization, if indicated, to determine the extent of the injury and the viability of the heart, for patients who do not survive as a donor organ.

Effect of high-hydrostatic pressure and moderate-intensity pulsed electric field on plum.

Moderate intensity pulse electric fields were applied in plum with the aim to increase bioactive compounds content of the fruit, while high-hydrostatic pressure was applied to preserve the purées. High-hydrostatic pressure treatment was compared with an equivalent thermal treatment. The addition of ascorbic acid during purée manufacture was also evaluated. The main objective of this study was to assess the effects on microorganisms, polyphenoloxidase, color and bioactive compounds of high-hydrostatic pressure, or thermal-processed plum purées made of moderate intensity pulse electric field-treated or no-moderate intensity pulse electric field-treated plums, after processing during storage. The application of moderate intensity pulse electric field to plums slightly increased the levels of anthocyanins and the antioxidant activity of purées. The application of Hydrostatic-high pressure (HHP) increased the levels of bioactive compounds in purées, while the thermal treatment preserved better the color during storage. The addition of ascorbic acid during the manufacture of plum purée was an important factor for the final quality of purées. The color and the bioactive compounds content were better preserved in purées with ascorbic acid. The no inactivation of polyphenoloxidase enzyme with treatments applied in this study affected the stability purées. Probably more intense treatments conditions (high-hydrostatic pressure and thermal treatment) would be necessary to reach better quality and shelf life during storage.

Avoiding the side effects of electric current pulse application to electroporated cells in disposable small volume cuvettes assures good cell survival.

BACKGROUND: The harmful side effects of electroporation to cells due to local changes in pH, the appearance of toxic electrode products, temperature increase, and the heterogeneity of the electric field acting on cells in the cuvettes used for electroporation were observed and discussed in several laboratories. If cells are subjected to weak electric fields for prolonged periods, for example in experiments on cell electrophoresis or galvanotaxis the same effects are seen. In these experiments investigators managed to reduce or eliminate the harmful side effects of electric current application. METHODS: For the experiments, disposable 20 µl cuvettes with two walls made of dialysis membranes were constructed and placed in a locally focused electric field at a considerable distance from the electrodes. Cuvettes were mounted into an apparatus for horizontal electrophoresis and the cells were subjected to direct current electric field (dcEF) pulses from a commercial pulse generator of exponentially declining pulses and from a custom-made generator of double and single rectangular pulses. RESULTS: More than 80% of the electroporated cells survived the dcEF pulses in both systems. Side effects related to electrodes were eliminated in both the flow through the dcEF and in the disposable cuvettes placed in the focused dcEFs. With a disposable cuvette system, we also confirmed the sensitization of cells to a dcEF using procaine by observing the loading of AT2 cells with calceine and using a square pulse generator, applying 50 ms single rectangular pulses. CONCLUSIONS: We suggest that the same methods of avoiding the side effects of electric current pulse application as in cell electrophoresis and galvanotaxis should also be used for electroporation. This conclusion was confirmed in our electroporation experiments performed in conditions assuring survival of over 80% of the electroporated cells. If the amplitude, duration, and shape of the dcEF pulse are known, then electroporation does not depend on the type of pulse generator. This knowledge of the characteristics of the pulse assures reproducibility of electroporation experiments using different equipment.

Tumor-specific frequencies and ocular melanoma.

Specific kilohertz frequencies in the environment from variable frequency drives on electric motors at a liquid natural gas compressor and storage station on a natural gas pipeline seem to be associated with the development of a very rare cancer, ocular melanoma, at a high school and in individuals living or working in a neighborhood near the plant. Primary neutral-to-earth oscilloscope voltage waveforms and spectra measured near the high school were nearly identical to the ground voltage 2.3 miles away at the gas pipeline. Peak frequencies of 7440 and 19,980 Hz were found at both places. The electric utility practice of using the earth as a conduit for return currents facilitated this exposure.

Influence of static electric field on cognition in mice.

With the rapid development of high voltage direct current transmission, the possibility of health effects associated with static electric field (SEF) has caused wide public concern. To examine the effects of long-lasting, full-body exposure to SEF on cognition, Institute of Cancer Research mice were exposed to SEF for 35 d. The intensities of SEF in experimental group I (EG-I), experimental group II (EG-II) and control group (CG) were 2.30∼15.40 kV/m, 9.20∼21.85 kV/m and 0 kV/m, respectively. The performance in learning and memory of mice were tested by Morris water maze (MWM) on days 2∼6, 16∼20 and 30∼34 during the exposure period. The concentrations of hippocampal amino acid neurotransmitters were evaluated on days 7, 21 and 35. Results showed that the latency in the MWM test had no significant difference among the EG-I, EG-II and CG (P > 0.05) during the exposure period. The percentage of time spent in the target quadrant was significantly decreased in the EG-II on day 34 during the exposure period (P < 0.05), whereas the percentage of time spent in the opposite quadrant increased markedly (P < 0.01). The glutamate and gamma-aminobutyric acid concentrations showed no significant differences among the EG-I, EG-II and CG (P > 0.05) during the exposure period. These results indicated that long-lasting, full-body exposure to SEF with certain intensity would not cause significant influence on learning ability, but it might associate with memory impairment of receptors. Meanwhile, this effect of memory impairment was dose-dependent and not causally linked to the glutamate and gamma-aminobutyric acid levels in the hippocampus.

Childhood leukaemia and distance from power lines in California: a population-based case-control study.

BACKGROUND: Studies have reported an increased risk of childhood leukaemia associated with living near high-voltage electric power transmission lines that extend to distances at which magnetic fields from lines are negligible. We conducted a large records-based case-control study of childhood leukaemia risk in the population living near power lines in California. METHODS: The study included 5788 childhood leukaemia and 3308 central nervous system (CNS) cancer cases (for comparison) born in and diagnosed in California (1986-2008), and matched to population-based controls by age and sex. We geocoded birth address and estimated the distance from residence to transmission lines using geographic information systems, aerial imagery, and, for some residences, site visits. RESULTS: For leukaemia, there was a slight excess of cases within 50 m of a transmission line over 200 kV (odds ratio 1.4, 95% confidence interval 0.7-2.7). There was no evidence of increased risk for distances beyond 50 m, for lower-voltage lines, or for CNS cancers. CONCLUSIONS: Our findings did not clearly support an increased childhood leukaemia risk associated with close proximity (<50 m) to higher voltage lines, but could be consistent with a small increased risk. Reports of increased risk for distances beyond 50 m were not replicated.

Mutagenic and genotoxic potential of direct electric current in Escherichia coli and Salmonella thyphimurium strains.

Direct electric current has several therapeutic uses such as antibacterial and antiprotozoal action, tissues scarring and regeneration, as well as tumor treatment. This method has shown promising results in vivo and in vitro, with significant efficacy and almost no side effects. Considering lack of studies regarding direct electric current mutagenic and/or genotoxic effects, the present work evaluated both aspects by using five different bacterial experimental assays: survival of repair-deficient mutants, Salmonella-histidine reversion mutagenesis (Ames test), forward mutations to rifampicin resistance, phage reactivation, and lysogenic induction. In these experimental conditions, cells were submitted to an approach that allows evaluation of anodic, cathodic, and electro-ionic effects generated by 2 mA of direct electric current, with doses ranging from 0.36 to 3.60 Coulombs. Our results showed these doses did not induce mutagenic or genotoxic effects.

Occupational exposures and Parkinson's disease mortality in a prospective Dutch cohort.

OBJECTIVES: We investigated the association between six occupational exposures (ie, pesticides, solvents, metals, diesel motor emissions (DME), extremely low frequency magnetic fields (ELF-MF) and electric shocks) and Parkinson's disease (PD) mortality in a large population-based prospective cohort study. METHODS: The Netherlands Cohort Study on diet and cancer enrolled 58,279 men and 62,573 women aged 55-69 years in 1986. Participants were followed up for cause-specific mortality over 17.3 years, until December 2003, resulting in 402 male and 207 female PD deaths. Following a case-cohort design, a subcohort of 5,000 participants was randomly sampled from the complete cohort. Information on occupational history and potential confounders was collected at baseline. Job-exposure matrices were applied to assign occupational exposures. Associations with PD mortality were evaluated using Cox regression. RESULTS: Among men, elevated HRs were observed for exposure to pesticides (eg, ever high exposed, HR 1.27, 95% CI 0.86 to 1.88) and ever high exposed to ELF-MF (HR 1.54, 95% CI 1.00 to 2.36). No association with exposure duration or trend in cumulative exposure was observed for any of the occupational exposures. Results among women were unstable due to small numbers of high-exposed women. CONCLUSIONS: Associations with PD mortality were observed for occupational exposure to pesticides and ELF-MF. However, the weight given to these findings is limited by the absence of a monotonic trend with either duration or cumulative exposure. No associations were found between PD mortality and occupational exposure to solvents, metals, DME or electric shocks.

Measurement and simulation of Joule heating during treatment of B-16 melanoma tumors in mice with nanosecond pulsed electric fields.

Experimental evidence shows that nanosecond pulsed electric fields (nsPEF) trigger apoptosis in skin tumors. We have postulated that the energy delivered by nsPEF is insufficient to impart significant heating to the treated tissue. Here we use both direct measurements and theoretical modeling of the Joule heating in order to validate this assumption. For the temperature measurement, thermo-sensitive liquid crystals (TLC) were used to determine the surface temperature while a micro-thermocouple (made from 30 µm wires) was used for measuring the temperature inside the tissue. The calculation of the temperature distribution used an asymptotic approach with the repeated calculation of the electric field, Joule heating and heat transfer, and the subsequent readjustment of the electrical tissue conductivity. This yields a temperature distribution both in space and time. It can be shown that for the measured increase in temperature an unexpectedly high electrical conductivity of the tissue would be required, which was indeed found by using voltage and current monitoring during the experiment. Using impedance measurements within t(after)=50 µs after the pulse revealed a fast decline of the high conductivity state when the electric field ceases. The experimentally measured high conductance of a skin fold (mouse) between plate electrodes was about 5 times higher than those of the maximally expected conductance due to fully electroporated membrane structures (G(max)/G(electroporated))≈5. Fully electroporated membrane structure assumes that 100% of the membranes are conductive which is estimated from an impedance measurement at 10 MHz where membranes are capacitively shorted. Since the temperature rise in B-16 mouse melanoma tumors due to equally spaced (Δt=2 s) 300 ns-pulses with E=40 kV/cm usually does not exceed ΔΤ=3 K at all parts of the skin fold between the electrodes, a hyperthermic effect on the tissue can be excluded.

Limiting electric fields of HVDC overhead power lines.

As a consequence of the increased use of renewable energy and the now long distances between energy generation and consumption, in Europe, electric power transfer by high-voltage (HV) direct current (DC) overhead power lines gains increasing importance. Thousands of kilometers of them are going to be built within the next years. However, existing guidelines and regulations do not yet contain recommendations to limit static electric fields, which are one of the most important criteria for HVDC overhead power lines in terms of tower design, span width and ground clearance. Based on theoretical and experimental data, in this article, static electric fields associated with adverse health effects are analysed and various criteria are derived for limiting static electric field strengths.

Effects of external electrical and magnetic fields on pacemakers and defibrillators: from engineering principles to clinical practice.

The overall risk of clinically significant adverse events related to EMI in recipients of CIEDs is very low. Therefore, no special precautions are needed when household appliances are used. Environmental and industrial sources of EMI are relatively safe when the exposure time is limited and distance from the CIEDs is maximized. The risk of EMI-induced events is highest within the hospital environment. Physician awareness of the possible interactions and methods to minimize them is warranted.

Association between exposure to electromagnetic fields from high voltage transmission lines and neurobehavioral function in children.

BACKGROUND: Evidence for a possible causal relationship between exposure to electromagnetic fields (EMF) emitted by high voltage transmission (HVT) lines and neurobehavioral dysfunction in children is insufficient. The present study aims to investigate the association between EMF exposure from HVT lines and neurobehavioral function in children. METHODS: Two primary schools were chosen based on monitoring data of ambient electromagnetic radiation. A cross-sectional study with 437 children (9 to 13 years old) was conducted. Exposure to EMF from HVT lines was monitored at each school. Information was collected on possible confounders and relevant exposure predictors using standardized questionnaires. Neurobehavioral function in children was evaluated using established computerized neurobehavioral tests. Data was analyzed using multivariable regression models adjusted for relevant confounders. RESULTS: After controlling for potential confounding factors, multivariable regression revealed that children attending a school near 500 kV HVT lines had poorer performance on the computerized neurobehavioral tests for Visual Retention and Pursuit Aiming compared to children attending a school that was not in close proximity to HVT lines. CONCLUSIONS: The results suggest long-term low-level exposure to EMF from HVT lines might have a negative impact on neurobehavioral function in children. However, because of differences in results only for two of four tests achieved statistical significance and potential limitations, more studies are needed to explore the effects of exposure to extremely low frequency EMF on neurobehavioral function and development in children.

Childhood leukaemia close to high-voltage power lines--the Geocap study, 2002-2007.

BACKGROUND: High-voltage overhead power lines (HVOLs) are a source of extremely low-frequency magnetic fields (ELF-MFs), which are classified as possible risk factors for childhood acute leukaemia (AL). The study was carried out to test the hypothesis of an increased AL incidence in children living close to HVOL of 225-400 kV (VHV-HVOL) and 63-150 kV (HV-HVOL). METHODS: The nationwide Geocap study included all the 2779 cases of childhood AL diagnosed in France over 2002-2007 and 30 000 contemporaneous population controls. The addresses at the time of inclusion were geocoded and precisely located around the whole HVOL network. RESULTS: Increased odds ratios (ORs) were observed for AL occurrence and living within 50 m of a VHV-HVOL (OR=1.7 (0.9-3.6)). In contrast, there was no association with living beyond that distance from a VHV-HVOL or within 50 m of a HV-HVOL. CONCLUSION: The present study, free from any participation bias, supports the previous international findings of an increase in AL incidence close to VHV-HVOL. In order to investigate for a potential role of ELF-MF in the results, ELF-MF at the residences close to HVOL are to be estimated, using models based on the annual current loads and local characteristics of the lines.