[Development of innovative methods of electromagnetic field evaluation for portable radio-station].

The results of portable radio-station "Radiy-301" electromagnetic fields (EMF) emission measurement and specific absorption rate data evaluation has shown that workers' exposure EMF levels may elevate hygienic norms and hereupon can be health risk factor. Possible way of portable radio-station EMF dosimetry enhancement by means of domestic and international approaches harmonization is considered.

Cancer cell proliferation is inhibited by specific modulation frequencies.

BACKGROUND: There is clinical evidence that very low and safe levels of amplitude-modulated electromagnetic fields administered via an intrabuccal spoon-shaped probe may elicit therapeutic responses in patients with cancer. However, there is no known mechanism explaining the anti-proliferative effect of very low intensity electromagnetic fields. METHODS: To understand the mechanism of this novel approach, hepatocellular carcinoma (HCC) cells were exposed to 27.12 MHz radiofrequency electromagnetic fields using in vitro exposure systems designed to replicate in vivo conditions. Cancer cells were exposed to tumour-specific modulation frequencies, previously identified by biofeedback methods in patients with a diagnosis of cancer. Control modulation frequencies consisted of randomly chosen modulation frequencies within the same 100 Hz-21 kHz range as cancer-specific frequencies. RESULTS: The growth of HCC and breast cancer cells was significantly decreased by HCC-specific and breast cancer-specific modulation frequencies, respectively. However, the same frequencies did not affect proliferation of nonmalignant hepatocytes or breast epithelial cells. Inhibition of HCC cell proliferation was associated with downregulation of XCL2 and PLP2. Furthermore, HCC-specific modulation frequencies disrupted the mitotic spindle. CONCLUSION: These findings uncover a novel mechanism controlling the growth of cancer cells at specific modulation frequencies without affecting normal tissues, which may have broad implications in oncology.

Long-term hepatitis B virus surface antigen decay in HIV-1/hepatitis B virus-coinfected adults initiating a tenofovir-containing regimen.

Hepatitis B virus (HBV) surface antigen (HBsAg) decay was explored in HIV-1- and HBV-coinfected patients beginning antiretroviral (ARV) therapy containing tenofovir disoproxil fumarate (TDF). The mean HBsAg decay was 0.38 log(10) IU/ml/year (95% confidence interval [CI], 0.71 to 0.05) in 18 patients with sustained plasma HIV-1 RNA suppression and 0.15 log(10) IU/ml/year (0.21 to 0.09) in 12 patients experiencing HIV-1 virologic failure due to suboptimal adherence to ARV (P = 0.17). We estimated that six of these 18 patients will attain HBsAg values below 10 IU/ml after 10 years of treatment.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields.

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC.

[Hereditary eye dieseas in the Entlebucher Mountaindog in Switzerland: a retrospective study from 1999 to 2009]. / Vererbte Augenerkrankungen beim Entlebucher Sennenhund in der Schweiz: Eine Retrospektive Studie von 1999 bis 2009.

The aim of this study was to analyze the prevalence and the incidence of hereditary cataract and progressive retinal atrophy (PRA) in the Entlebucher Mountaindog (EMD) and to evaluate possible changes over time. In addition, the influence of selective breeding programs and DNA-testing for PRA was also investigated. Data of eye certifications for hereditary eye diseases was used. Between 1999 and 2009 a total of 798 ocular examinations were carried out in 285 EMD. 20.4 % had cataracts and 69 % of these were of the posterior polar type. PRA was diagnosed in 6.3 % of the dogs. Cataracts were diagnosed at 5.24 ± 2.71 years (mean ± standard error), while PRA was diagnosed at 4.93 ± 1.32 years of age. The incidence of PRA and cataract showed a decreasing trend (p-value > 0.2) without being significant.

Measurement, simulation and uncertainty assessment of implant heating during MRI.

The heating of tissues around implants during MRI can pose severe health risks, and careful evaluation is required for leads to be labeled as MR conditionally safe. A recent interlaboratory comparison study has shown that different groups can produce widely varying results (sometimes with more than a factor of 5 difference) when performing measurements according to current guidelines. To determine the related difficulties and to derive optimized procedures, two different generic lead structures have been investigated in this study by using state-of-the-art temperature and dosimetric probes, as well as simulations for which detailed uncertainty budgets have been determined. The agreement between simulations and measurements is well within the combined uncertainty. The study revealed that the uncertainty can be kept below 17% if appropriate instrumentation and procedures are applied. Optimized experimental assessment techniques can be derived from the findings presented herein.

Improved quality of samples and laboratory turnaround time using 3.5 mL low vacuum BD Vacutainer® Barricor tubes in the emergency department.

BACKGROUND: Centrifugation is a consuming time step which participates to increase the turnaround time (TAT) in laboratories, likewise hemolysis sample that needs a re-sampling could delay management of patients. Recently, it has been postulated that BD Barricor™ tube could allow to decrease the centrifugation time and prevent hemolysis, two key feature to ensure high-quality results.Aim of the study was to evaluate the impact of replacing 4 mL BD vacutainer heparin lithium tube by low vacuum 3.5 mL BD vacutainer Barricor™ tube in an emergency department (ED) on hemolysis rate and TAT. METHODS: Data of hemolysis index (HI) and TAT were compared between the first period of 15 days using 4 mL BD vacutainer heparin lithium tubes with 15 min at 2000xg as centrifugation setting and a second period of 15 days using BD vacutainer Barricor™ tube centrifuged 3 min at 4000xg. RESULTS: A significantly reduced time duration between reception of sample and available results in informatics lab system was observed with the reduction time of centrifugation allowed by use of Barricor™ tube compared to regular heparin lithium tubes (p < 0.001). A significative decrease in hemolysis rate also occurred in the second period as samples with HI < 10 reached from 52.5% in the first period to 68.5% (p < 0.001) in the second. CONCLUSION: Low vacuum BarricorTM tubes allowing a higher speed of centrifugation improve lab TAT without impairment of sample quality as a significant reduction of hemolysis was observed, a double advantage which is of particular interest for ED.

Novel hyperthermia applicator system allows adaptive treatment planning: Preliminary clinical results in tumour-bearing animals.

Hyperthermia (HT) as an adjuvant to radiation therapy (RT) is a multimodality treatment method to enhance therapeutic efficacy in different tumours. High demands are placed on the hardware and treatment planning software to guarantee adequately planned and applied HT treatments. The aim of this prospective study was to determine the effectiveness and safety of the novel HT system in tumour-bearing dogs and cats in terms of local response and toxicity as well as to compare planned with actual achieved data during heating. A novel applicator with a flexible number of elements and integrated closed-loop temperature feedback control system, and a tool for patient-specific treatment planning were used in a combined thermoradiotherapy protocol. Good agreement between predictions from planning and clinical outcome was found in 7 of 8 cases. Effective HT treatments were planned and verified with the novel system and provided improved quality of life in all but 1 patient. This individualized treatment planning and controlled heat exposure allows adaptive, flexible and safe HT treatments in palliatively treated animal patients.

Novel conformal technique to reduce staircasing artifacts at material boundaries for FDTD modeling of the bioheat equation.

The modeling of thermal effects, often based on the Pennes Bioheat Equation, is becoming increasingly popular. The FDTD technique commonly used in this context suffers considerably from staircasing errors at boundaries. A new conformal technique is proposed that can easily be integrated into existing implementations without requiring a special update scheme. It scales fluxes at interfaces with factors derived from the local surface normal. The new scheme is validated using an analytical solution, and an error analysis is performed to understand its behavior. The new scheme behaves considerably better than the standard scheme. Furthermore, in contrast to the standard scheme, it is possible to obtain with it more accurate solutions by increasing the grid resolution.

Effects of geometry discretization aspects on the numerical solution of the bioheat transfer equation with the FDTD technique.

In this work, we highlight two issues that have to be taken into consideration for accurate thermal modelling with the finite-difference time-domain (FDTD) method, namely the tissue interfaces and the staircasing effect. The former appears less critical in the overall accuracy of the results, whereas the latter may have an influence on the worst-case approach used in numerical dosimetry of non-ionizing radiation.

Characterization of the electromagnetic near-field absorption in layered biological tissue in the frequency range from 30 MHz to 6,000 MHz.

Currently, standards for the compliance testing of wireless devices are being extended to cover a wider frequency band and different usage patterns of mobile phones as well as of novel body-worn and handheld devices. As a consequence, not only the head but also strongly varying tissue distributions of the body are exposed to electromagnetic radiation. Several authors have reported changes in the SAR absorption of body tissue due to the presence of a low permittivity fat layer. This paper identifies two different effects which can lead to increased SAR in layered tissue in comparison to the SAR assessed using homogeneous tissue simulating liquid: (1) for larger distances between the tissue and the antenna, standing wave effects occur depending on the frequency and fat layer thickness. (2) In the very close near-field (distances approximately lambda/40), reactive E-field components lead to high local absorption in the skin. The latter effect occurs at lower frequencies and depends on the antenna type. Modification of the parameters of the homogeneous liquids cannot compensate for these effects. However, a conservative exposure estimate can be obtained by applying a multiplication factor between 1 and 3 to the values assessed using current experimental dosimetric techniques.

Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats exposed to frequency-modulated microwave fields.

In a 2-year bioassay, we exposed Fischer 344 rats to a frequency-modulated (FM) signal (836.55 MHz +/- 12.5 KHz deviation) simulating radiofrequency exposures in the head of users of hand-held mobile phones. We tested for effects on spontaneous tumorigenicity of central nervous system (CNS) tumors in the offspring of pregnant rats and also for modified incidence of primary CNS tumors in rats treated with a single dose of the neurocarcinogen ethylnitrosourea (ENU) in utero. ENU dosage (4 mg/kg) was selected to give an expected brain tumor incidence of 10-15% over the mean life span of 26 months. Pregnant dams (n = 102) were randomly assigned to six groups. Their offspring were treated as cohorts in each of the six groups (n = 90 per group; total, n = 540): Sham ENU/Sham Field, Sham ENU/Field Exposed, ENU/Sham Field, ENU/Field Exposed, ENU/Cage Control, and Sham ENU/Cage Control. Intermittent field exposures began on gestation day 19 and continued until weaning at 21 days, resuming thereafter at 31 days and continuing until experiment termination at 731-734 days. Energy absorption rates (SARs) in the rats' brains were similar to localized peak brain exposures of a phone user (female, 236 g, 1.0 W/kg; male, 450 g, 1.2 W/kg). Of the original 540 rats, 168 died before the termination of the experiment. In these rats, ENU significantly reduced survival from a mean of 708 days in three groups without ENU treatment to 645 days in three groups treated with ENU (P < 0.0005). There were no effects on survival attributable to FM field exposure in either ENU-treated or in sham-treated groups. Spontaneous CNS tumor incidence in control groups was 1.1-4.4% but sharply higher in rats receiving ENU (14.4-22.2%; P < 0.0001). No FM field-mediated changes were observed in number, incidence, or histological type of either spontaneous or ENU-induced brain tumors, nor were gender differences detected in tumor numbers. These negative findings with FM fields contrast with our study using standard digital phone fields pulsed on and off at 50/se, where a trend was noted toward reduced incidence of both spontaneous and ENU-induced CNS tumors (W. R. Adey et al., Radiat. Res., 152: 293-302, 1999). Although consistent but not attaining significance in the experiment overall (spontaneous CNS tumors, P < 0.08 one-tailed; P < 0.16 two-tailed; ENU-induced CNS tumors, P < 0.08 one-tailed, P < 0.16 two-tailed), the trend was significant (P < 0.015 one-tailed, P < 0.03, two-tailed) in rats that received ENU and died prior to experiment termination, with a primary brain tumor as the cause of death. We discuss differences in the signaling structure of digital and FM fields. Certain bioeffects induced by either amplitude-modulated or pulsed radiofrequency fields at athermal levels have not been seen with fields of similar average power but unvarying in intensity (continuous wave or frequency-modulated fields).

Magnetic nanoparticle-induced hyperthermia with appropriate payloads: Paul Ehrlich's "magic (nano)bullet" for cancer theranostics?

Effective multimodal cancer management requires the optimal integration of diagnostic and therapeutic modalities. Radiation therapy, chemotherapy and immunotherapy, alone or in combination, are integral parts of various cancer treatment protocols. Hyperthermia at 39-45°C is a potent radiosensitiser and has been shown to improve therapeutic outcomes in various tumours through its synergy with chemotherapy. Gene silencing approaches, using small interfering RNAs and microRNAs, are also being explored in clinical trials in oncology. The rapid developments in multifunctional nanoparticles provide ample opportunities to integrate both diagnostic and therapeutic modalities into a single effective cancer "theranostic" vector. Nanoparticles could extravasate passively into the tumour tissues in preference to the adjacent normal tissues by capitalizing on the enhanced permeability and retention effect. Tumour targeting might be further augmented by conjugating tumour-specific peptides and antibodies onto the surface of these nanoparticles or by activation through electromagnetic radiations, laser or ultrasound. Magnetic nanoparticles can induce hyperthermia in the presence of an alternating magnetic field, thereby multifunctionally with tumour-specific payloads empowering tumour specific radiotheranostics (for both imaging and radiotherapy), chemotherapy drug delivery, immunotherapy and gene silencing therapy. Such a (nano)bullet could realise the "magic bullet" conceived by Paul Ehrlich more than a century ago. This article discusses the various aspects of this "magic (nano)bullet" and the challenges that need to be addressed to usher in this new paradigm in modern cancer diagnostics and therapeutics.

Response, thermal regulatory threshold and thermal breakdown threshold of restrained RF-exposed mice at 905 MHz.

The objective of this study was the determination of the thermal regulatory and the thermal breakdown thresholds for in-tube restrained B6C3F1 and NMRI mice exposed to radiofrequency electromagnetic fields at 905 MHz. Different levels of the whole-body averaged specific absorption rate (SAR = 0, 2, 5, 7.2, 10, 12.6 and 20 W kg(-1)) have been applied to the mice inside the 'Ferris Wheel' exposure setup at 22 +/- 2 degrees C and 30-70% humidity. The thermal responses were assessed by measurement of the rectal temperature prior, during and after the 2 h exposure session. For B6C3F1 mice, the thermal response was examined for three different weight groups (20 g, 24 g, 29 g), both genders and for pregnant mice. Additionally, NMRI mice with a weight of 36 g were investigated for an interstrain comparison. The thermal regulatory threshold of in-tube restrained mice was found at SAR levels between 2 W kg(-1) and 5 W kg(-1), whereas the breakdown of regulation was determined at 10.1 +/- 4.0 W kg(-1)(K = 2) for B6C3F1 mice and 7.7 +/- 1.6 W kg(-1)(K = 2) for NMRI mice. Based on a simplified power balance equation, the thresholds show a clear dependence upon the metabolic rate and weight. NMRI mice were more sensitive to thermal stress and respond at lower SAR values with regulation and breakdown. The presented data suggest that the thermal breakdown for in-tube restrained mice, whole-body exposed to radiofrequency fields, may occur at SAR levels of 6 W kg(-1)(K = 2) at laboratory conditions.

Effect of global system for mobile communication microwave exposure on the genomic response of the rat brain.

The acute effect of global system for mobile communication (GSM) microwave exposure on the genomic response of the central nervous system was studied in rats by measuring changes in the messenger RNAs of hsp70, the transcription factor genes c-fos and c-jun and the glial structural gene GFAP using in situ hybridization histochemistry. Protein products of transcription factors, stress proteins and marker proteins of astroglial and microglial activation were assessed by immunocytochemistry. Cell proliferation was evaluated by bromodeoxyuridine incorporation. A special GSM radiofrequency test set, connected to a commercial cellular phone operating in the discontinuous transmission mode, was used to simulate GSM exposure. The study was conducted at time averaged and brain averaged specific absorption rates of 0.3 W/kg (GSM exposure), 1.5 W/kg (GSM exposure) and 7.5 W/kg (continuous wave exposure), respectively. Immediately after exposure, in situ hybridization revealed slight induction of hsp70 messenger RNA in the cerebellum and hippocampus after 7.5 W/kg exposure, but not at lower intensities. A slightly increased expression of c-fos messenger RNA was observed in the cerebellum, neocortex and piriform cortex of all groups subjected to immobilization, but no differences were found amongst different exposure conditions. C-jun and GFAP messenger RNAs did not increase in any of the experimental groups. 24 h after exposure, immunocytochemical analysis of FOS and JUN proteins (c-FOS, FOS B, c-JUN JUN B, JUN D), of HSP70 or of KROX-20 and -24 did not reveal any alterations. Seven days after exposure, neither increased cell proliferation nor altered expression of astroglial and microglial marker proteins were observed. In conclusion, acute high intensity microwave exposure of immobilized rats may induce some minor stress response but does not result in lasting adaptive or reactive changes of the brain.

Effects of low energy emission therapy in chronic psychophysiological insomnia.

The treatment of chronic psychophysiological insomnia presents a challenge that has not been met using currently available pharmacotherapy. Low energy emission therapy (LEET) has been developed as a potential alternative therapy for this disorder. LEET consists of amplitude-modulated electromagnetic fields delivered intrabuccally by means of an electrically conducting mouthpiece in direct contact with the oral mucosa. The effect of LEET on chronic psychophysiological insomnia was assessed with polysomnography (PSG) and sleep rating forms on a total of 106 patients at two different centers. Active or inactive LEET was administered for 20 minutes in late afternoon three times a week for a total of 12 treatments. Primary efficacy endpoints evaluating the results were changes from baseline in PSG-assessed total sleep time (TST) and sleep latency (SL). Secondary endpoints were changes in sleep efficiency (SE), sleep stages, and reports by the subjects of SL and TST. There was a significant increase in TST as assessed by PSG between baseline and post-treatment values for the active treatment group (76.0 +/- 11.1 minutes, p = 0.0001). The increase for the inactive treatment group was not statistically significant. The TST improvement was significantly greater for the active group when compared to the inactive group (adjusted for baseline TST; p = 0.020. R1 = 0.20). There was a significant decrease in SL as assessed by PSG between baseline and post-treatment values for the active treatment group (-21.6 +/- 5.9 minutes, p = 0.0006), whereas the decrease noted for the inactive treatment group was not statistically significant. The difference in SL decrease between the two treatment groups was marginally significant (adjusted for baseline SL and center, p = 0.068, R2 = 0.60). The number of sleep cycles per night increased by 30% after active treatment (p = 0.0001) but was unchanged following inactive treatment. Subjects did not experience rebound insomnia, and there were no significant side effects. The data presented in this report indicate that LEET administered for 20 minutes three times a week increased TST and reduced SL in chronic psychophysiological insomnia. LEET is safe and well tolerated and it effectively improved the sleep of chronic insomniacs given 12 treatments over a 4-week period by increasing the number of sleep cycles without altering the percentage of the various sleep stages during the night. The therapeutic action of LEET differs from that of currently available drug therapies in that the sleep pattern noted in insomniacs following LEET treatment more closely resembles nocturnal physiological sleep. This novel treatment may offer an attractive alternative therapy for chronic insomnia.

Spontaneous and nitrosourea-induced primary tumors of the central nervous system in Fischer 344 rats chronically exposed to 836 MHz modulated microwaves.

We have tested an 836.55 MHz field with North American Digital Cellular (NADC) modulation in a 2-year animal bioassay that included fetal exposure. In offspring of pregnant Fischer 344 rats, we tested both spontaneous tumorigenicity and the incidence of induced central nervous system (CNS) tumors after a single dose of the carcinogen ethylnitrosourea (ENU) in utero, followed by intermittent digital-phone field exposure for 24 months. Far-field exposures began on gestational day 19 and continued until weaning at age 21 days. Near-field exposures began at 35 days and continued for the next 22 months, 4 consecutive days weekly, 2 h/day. SAR levels simulated localized peak brain exposures of a cell phone user. Of the 236 original rats, 182 (77%) survived to the termination of the whole experiment and were sacrificed at age 709-712 days. The 54 rats (23%) that died during the study ("preterm rats") formed a separate group for some statistical analyses. There was no evidence of tumorigenic effects in the CNS from exposure to the TDMA field. However, some evidence of tumor-inhibiting effects of TDMA exposure was apparent. Overall, the TDMA field-exposed animals exhibited trends toward a reduced incidence of spontaneous CNS tumors (P < 0. 16, two-tailed) and ENU-induced CNS tumors (P < 0.16, two-tailed). In preterm rats, where primary neural tumors were determined to be the cause of death, fields decreased the incidence of ENU-induced tumors (P < 0.03, two-tailed). We discuss a possible approach to evaluating with greater certainty the possible inhibitory effects of TDMA-field exposure on tumorigenesis in the CNS.

Exposure to pulsed high-frequency electromagnetic field during waking affects human sleep EEG.

The aim of the study was to investigate whether the electromagnetic field (EMF) emitted by digital radiotelephone handsets affects brain physiology. Healthy, young male subjects were exposed for 30 min to EMF (900 MHz; spatial peak specific absorption rate 1 W/kg) during the waking period preceding sleep. Compared with the control condition with sham exposure, spectral power of the EEG in non-rapid eye movement sleep was increased. The maximum rise occurred in the 9.75-11.25 Hz and 12.5-13.25 Hz band during the initial part of sleep. These changes correspond to those obtained in a previous study where EMF was intermittently applied during sleep. Unilateral exposure induced no hemispheric asymmetry of EEG power. The present results demonstrate that exposure during waking modifies the EEG during subsequent sleep. Thus the changes of brain function induced by pulsed high-frequency EMF outlast the exposure period.

Analysis of EEG data from weak-field magnetic stimulation of mesial temporal lobe epilepsy patients.

Ten patients suffering from mesial temporal lobe epilepsy were exposed to weak, DC magnetic field stimulation following computer-controlled protocols established in previous studies. Poisson statistical analysis of the ten patients undergoing semi-invasive (foramen ovale) electrode monitoring reveals that for at least one experimental protocol, application of DC magnetic fields alters interictal epileptiform spike activity in five of ten patients. Similar results also have been observed in the analysis of both human and rat brains by employing weak, alternating magnetic field stimulation. Further study is necessary in order to optimize the magnetic field exposure protocol.

1800 MHz radiofrequency (mobile phones, different Global System for Mobile communication modulations) does not affect apoptosis and heat shock protein 70 level in peripheral blood mononuclear cells from young and old donors.

PURPOSE: To study if prolonged in vitro exposure to 1800MHz radiofrequency (RF) could exert an effect on human peripheral blood mononuclear cells (PBMC) from young and elderly donors by affecting apoptosis, mitochondrial membrane potential and heat shock protein (HSP) 70 levels. MATERIALS AND METHODS: Endpoints were analysed in the presence or absence of the apoptosis-inducing agent 2-deoxy-D-ribose. Three different signal modulations typical of the Global System for Mobile communication (GSM) system were applied. The modulations are widely used in mobile telephony (GSM Basic, discontinuous transmission [DTX] and Talk) at specific absorption rates of 1.4 and 2.0 W kg(-1). RESULTS: In all conditions and for all endpoints tested, there was no significant difference between RF- and sham-exposed cells. CONCLUSION: 1800MHz RF could not induce apoptosis by itself or affect the apoptotic phenomenon when induced by an apoptotic agent. Moreover, RF did not modify the mitochondrial functionality and the expression of HSP 70.