Repeated electromagnetic field stimulation lowers amyloid-ß peptide levels in primary human mixed brain tissue cultures.

Late Onset Alzheimer's Disease is the most common cause of dementia, characterized by extracellular deposition of plaques primarily of amyloid-ß (Aß) peptide and tangles primarily of hyperphosphorylated tau protein. We present data to suggest a noninvasive strategy to decrease potentially toxic Aß levels, using repeated electromagnetic field stimulation (REMFS) in primary human brain (PHB) cultures. We examined effects of REMFS on Aß levels (Aß40 and Aß42, that are 40 or 42 amino acid residues in length, respectively) in PHB cultures at different frequencies, powers, and specific absorption rates (SAR). PHB cultures at day in vitro 7 (DIV7) treated with 64 MHz, and 1 hour daily for 14 days (DIV 21) had significantly reduced levels of secreted Aß40 (p = 001) and Aß42 (p = 0.029) peptides, compared to untreated cultures. PHB cultures (DIV7) treated at 64 MHz, for 1 or 2 hour during 14 days also produced significantly lower Aß levels. PHB cultures (DIV28) treated with 64 MHz 1 hour/day during 4 or 8 days produced a similar significant reduction in Aß40 levels. 0.4 W/kg was the minimum SAR required to produce a biological effect. Exposure did not result in cellular toxicity nor significant changes in secreted Aß precursor protein-α (sAPPα) levels, suggesting the decrease in Aß did not likely result from redirection toward the α-secretase pathway. EMF frequency and power used in our work is utilized in human magnetic resonance imaging (MRI, thus suggesting REMFS can be further developed in clinical settings to modulate Aß deposition.

No Increased DNA Damage Observed in the Brain, Liver, and Lung of Fetal Mice Treated With Ethylnitrosourea and Exposed to UMTS Radiofrequency Electromagnetic Fields.

The widespread use of mobile phones and Wi-Fi-based communication devices makes exposure to radiofrequency electromagnetic fields (RF-EMF) unavoidable. Previous experiments have revealed the tumor-promoting effects of non-ionizing RF-EMF in adult carcinogen-treated mice in utero. To extend these investigations, we tested whether these effects are due to the co-carcinogenicity of RF-EMF which would manifest as elevated DNA damage. Similar to previous experiments, pregnant mice were exposed to RF-EMF (Universal Mobile Telecommunication System [UMTS] standard, approximately 1,960 MHz) from day 7 post-conception (p.c.) at 0 (sham), 0.04, and 0.4 W/kg SAR. At day 14 p.c., the mice were injected with the carcinogen ethylnitrosourea (ENU, 40 mg/kg). At three time-points specifically 24, 36, and 72 h later, the pregnant females were sacrificed and the fetuses (n = 24-57) were removed. A dye (cy3) specific for adenyl adducts was used to detect DNA damage by fluorescence microscopy in the brain, liver, and lung of each fetus. Compared to control (0 W/kg SAR), exposure to RF-EMF had no effect on the formation of DNA adducts in the inspected tissues. We conclude that increased adenyl formation of DNA by RF-EMF exposure is not a valid explanation for the previously reported tumor-promoting effects of RF-RMF. Our findings may help to gain a deeper insight into the biological effects of RF-EMF exposure in the context of malignancy. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.

Multigenerational exposure to uranium changes morphometric parameters and global DNA methylation in rat sperm.

There is increasing evidence that environmental exposures early in fetal development influence phenotype and give rise to disease risk in the next generations. We previously found that lifelong exposure to uranium, an environmental contaminant, induced subtle testicular and hormonal defects; however, its impact on the reproductive system of multiple subsequent generations was unexplored. Herein, rats were exposed to a supra-environmental and non-nephrotoxic concentration of natural uranium (U, 40 mg·L-1 of drinking water) from postnatal life to adulthood (F0), during fetal life (F1), and only as the germ cells from the F1 generation (F2). General parameters (reproductive indices, epididymal weight) and sperm morphology were assessed in the three generations. In order to identify the epigenetic effects of U, we analyzed also the global DNA methylation profile and described for the first time the mRNA expression levels of markers involved in the (de)methylation system in rat epididymal spermatozoa. Our results showed that the F1 generation had a reduced pregnancy rate. Despite the sperm number being unmodified, sperm morphology was affected in the F0, F1 and F2 generations. Morphometric analysis for ten parameters was detailed for each generation. No common parameter was detected between the three generations, but the head and the middle-piece were always modified in the abnormal sperms. In the F1 U-exposed generation, the total number of abnormal sperm was significantly higher than in the F0 and F2 generations, suggesting that fetal exposure to uranium was more deleterious. This effect could be associated with the pregnancy rate to produce the F2 generation. Interestingly, global DNA methylation analysis showed also hypomethylation in the sperm DNA of the last F2 generation. In conclusion, our study demonstrates that uranium can induce morphological sperm defects and changes in the DNA methylation level after multigenerational exposure. The epigenetic transgenerational inheritance of U-induced reproductive defects should be assessed in further experiments.

Occupational and patient radiation doses in a modern cardiac electrophysiology laboratory.

PURPOSE: Technological advancements have greatly expanded the field of cardiac electrophysiology, requiring greater demands on imaging systems and potentially delivering higher radiation doses to patients and operators. With little contemporary research on occupational and patient radiation risk in the electrophysiology laboratory, the aim of this study was to analyze radiation doses, including occupational fetal doses, over approximately the last decade. We benchmarked the occupational data to our patient radiation dose data to allow for comparison and to put into perspective the associated radiation risks. METHODS: Occupational radiation dosimetry analyzed included data from an 11-year period for physicians, a 7-year period for nurses, and a 9-year period for fetal doses. Patient-related dose metrics over an 8-year period were also analyzed. RESULTS: In the physician and nursing groups, there was a nearly 70% decrease in the average occupational radiation doses over the given periods. Within the electrophysiology department, the average fetal occupational doses were very low, close to 0 µSv. The average reference point air kerma per patient for all electrophysiology procedures decreased from nearly 600 mGy/procedure in 2010 to just over 100 mGy/procedure in 2017. CONCLUSIONS: Patient and occupational radiation doses in our laboratories significantly decreased over the periods analyzed as a result of clinical and technical staff efforts as well as advances in imaging technology. The radiation-related risk to individuals working in our electrophysiology laboratories, including pregnant women, is very low. Data reported herein could be used by other institutions to evaluate their occupational and patient radiation safety practices.

Minimal use of fluoroscopy to reduce fetal radiation exposure during radiofrequency catheter ablation of maternal supraventricular tachycardia.

Electrophysiologic procedures in the young engender concern about the potential long-term effects of radiation exposure. This concern is manifold if such procedures are contemplated during pregnancy. Catheter ablations in pregnancy are indicated only in the presence of an unstable tachycardia that cannot be controlled by antiarrhythmic agents. This report describes the case of an 18-year-old pregnant woman and our stratagem to minimize irradiation of the mother and the fetus.

A High-Order, Symplectic, Finite-Difference Time-Domain Scheme for Bioelectromagnetic Applications within the Mother/Fetus Model.

An explicit high-order, symplectic, finite-difference time-domain (SFDTD) scheme is applied to a bioelectromagnetic simulation using a simple model of a pregnant woman and her fetus. Compared to the traditional FDTD scheme, this scheme maintains the inherent nature of the Hamilton system and ensures energy conservation numerically and a high precision. The SFDTD scheme is used to predict the specific absorption rate (SAR) for a simple model of a pregnant female woman (month 9) using radio frequency (RF) fields from 1.5 T and 3 T MRI systems (operating at approximately 64 and 128 MHz, respectively). The results suggest that by using a plasma protective layer under the 1.5 T MRI system, the SAR values for the pregnant woman and her fetus are significantly reduced. Additionally, for a 90 degree plasma protective layer, the SAR values are approximately equal to the 120 degree layer and the 180 degree layer, and it is reduced relative to the 60 degree layer. This proves that using a 90 degree plasma protective layer is the most effective and economical angle to use.

Fetus sound stimulation: cilia memristor effect of signal transduction.

BACKGROUND: This experimental study evaluates fetal middle cerebral artery (MCA) circulation after the defined prenatal acoustical stimulation (PAS) and the role of cilia in hearing and memory and could explain signal transduction and memory according to cilia optical-acoustical properties. METHODS: PAS was performed twice on 119 no-risk term pregnancies. We analyzed fetal MCA circulation before, after first and second PAS. RESULTS: Analysis of the Pulsatility index basic (PIB) and before PAS and Pulsatility index reactive after the first PAS (PIR 1) shows high statistical difference, representing high influence on the brain circulation. Analysis of PIB and Pulsatility index reactive after the second PAS (PIR 2) shows no statistical difference. Cilia as nanoscale structure possess magnetic flux linkage that depends on the amount of charge that has passed between two-terminal variable resistors of cilia. Microtubule resistance, as a function of the current through and voltage across the structure, leads to appearance of cilia memory with the "memristor" property. CONCLUSION: Acoustical and optical cilia properties play crucial role in hearing and memory processes. We suggest that fetuses are getting used to sound, developing a kind of memory patterns, considering acoustical and electromagnetically waves and involving cilia and microtubules and try to explain signal transduction.

Effect of puerarin on matrix metalloproteinase-2 in human fetal scleral fibroblasts treated with low frequency electromagnetic fields.

OBJECTIVE: To study the effect of puerarin on matrix metalloproteinase-2 (MMP-2) gene and protein expression in human fetal scleral fibroblasts (HFSFs) exposed to extremely low frequency electromagnetic fields (ELF-EMF). METHODS: Cultured HFSFs were exposed to 0.2 mT ELF-EMF for 24 h. The experimental groups were divided into subgroups treated with 0, 0.1, 1 and 10 microM puerarin respectively. The expression of MMP-2 mRNA and protein were detected with real-time polymerase chain reaction and western-blot analysis respectively. RESULTS: MMP-2 mRNA and protein expression increased by 0.793 and 1.130 folds respectively under the exposure of ELF-EMFs at 0.2 mT flux density for 24 h. Puerarin at the concentration of 0.1 microM reversed this effect by 8.53% in mRNA and by 17.97% in protein expression (P < 0.05). The effect was more prominent at higher concentrations (1 and 10 microM, P < 0.01). CONCLUSION: Exposure to ELF-EMFs increased the expression of MMP-2 mRNA and protein in HFSF cells. Puerarin reversed the action to some extent in a specific concentration range. Our results implied that the puerarin might protect scleral tissue from increased expression induced by exposure to ELF-EMFs.

Adaptive response of low linear energy transfer X-rays for protection against high linear energy transfer accelerated heavy ion-induced teratogenesis.

BACKGROUND: Adaptive response (AR) of low linear energy transfer (LET) irradiations for protection against teratogenesis induced by high LET irradiations is not well documented. In this study, induction of AR by X-rays against teratogenesis induced by accelerated heavy ions was examined in fetal mice. METHODS: Irradiations of pregnant C57BL/6J mice were performed by delivering a priming low dose from X-rays at 0.05 or 0.30 Gy on gestation day 11 followed one day later by a challenge high dose from either X-rays or accelerated heavy ions. Monoenergetic beams of carbon, neon, silicon, and iron with the LET values of about 15, 30, 55, and 200 keV/µm, respectively, were examined. Significant suppression of teratogenic effects (fetal death, malformation of live fetuses, or low body weight) was used as the endpoint for judgment of a successful AR induction. RESULTS: Existence of AR induced by low-LET X-rays against teratogenic effect induced by high-LET accelerated heavy ions was demonstrated. The priming low dose of X-rays significantly reduced the occurrence of prenatal fetal death, malformation, and/or low body weight induced by the challenge high dose from either X-rays or accelerated heavy ions of carbon, neon or silicon but not iron particles. CONCLUSIONS: Successful AR induction appears to be a radiation quality event, depending on the LET value and/or the particle species of the challenge irradiations. These findings would provide a new insight into the study on radiation-induced AR in utero.

Cleft lip and palate in Madagascar 1998-2007.

Our aim was to find out the prevalence of oral clefts in Madagascar, to compare it with elsewhere in the world, and to give the possible cause of the particular rate in the Vakinankaratra region where Antsirabe is situated. Data were collected from birth registers from 1998 to 2007 in the 10 most important hospitals of the 6 former provinces and of Antsirabe. A total of 150,973 consecutive live births were recorded in the 6 provinces, and 175,981 including those from Antsirabe. The general birth prevalence of oral clefts was 0.48‰ (about 1/2100, n=150,973) which was made up of 0.23‰, 0.12‰, and 0.11‰ for cleft lip and palate, isolated cleft lip, and isolated cleft palate, respectively. Prevalence was greater on the Central Highlands than in the coastal regions. Higher prevalence rates were found among girls than boys (64.4% compared with 35.6%, p<0.01). Of the clefts, 65.5% were unilateral, and left-sided ones were most common (77.8%). If the results obtained in Antsirabe are also considered, birth prevalence of oral clefts was 0.92‰ (about 1/1100, n=175,981) if Antsirabe is included, and 0.41-0.50‰ in the 6 former provinces; rates of associated, or syndromic, forms, or both, were 21.9% in the 6 provinces and 26.1% in Antsirabe. Overall, the prevalence of oral clefts in Madagascar does not differ from that in the rest of the world, except for the sex difference. There was a high prevalence of oral clefts in general and associated or syndromic forms, or both, in the Vakinankaratra region. There may be a link between these results and background high doses of ionising radiation in some areas because of the presence of former uranium mines. Further research is needed to obtain more precise data.

Fetal auditory responses to external sounds and mother's heart beat: detection improved by Independent Component Analysis.

In this paper, we present a magnetoencephalographic study of the fetal auditory response to external stimuli and to the sound of the mother's heartbeat. We describe how an ad hoc functional selection procedure allowed us to isolate the sources in the fetal brain responding to sounds only, after the application to the recorded data of a standard Independent Component Analysis algorithm. In our experiment, acoustic stimuli were delivered to twelve healthy women with uncomplicated pregnancies at a time between 36 and 40 weeks gestational age, with their fetuses in breech presentation. Ultrasound images allowed determination of the region over the women's abdomen nearest to the fetal head, over which both the acoustic stimulator and the MEG sensors were subsequently placed. In 8 out of the 12 cases, our analysis provided consistent evidence of a fetal response both to the mother's heartbeat and to the external auditory stimulation; both were characterized by a clear prominent component at around 200 ms latency, which is widely accepted as the marker of the fetal response to auditory stimuli.

Internal barium shielding to minimize fetal irradiation in spiral chest CT: a phantom simulation experiment.

PURPOSE: To use a phantom to prospectively examine the attenuating effect of barium sulfate as an internal shield to protect the fetus. MATERIALS AND METHODS: In an adult-size phantom, 1- and 2-cm-thick acrylic slabs containing 315 or 630 mL of water, 2% or 40% barium sulfate suspension, and a 1-mm lead sheet were placed under the diaphragm. In 17 experiments, fetal dose was measured by using thermoluminescent dosimeters that were placed immediately under (near field) and 10 cm below (far field) the water slab (eight experiments), barium sulfate slab (eight experiments), and lead sheet (one experiment). In a pulmonary embolism protocol, the phantom was scanned with single-detector spiral computed tomography (CT) at 130 kVp and 230 mAs. RESULTS: The control radiation dose was 3.60 mSv+/-0.54 (standard deviation) with the water slab at near field, where the uterus dome is at near term, and 0.507 mSv+/-0.07 with the water slab at far field, the uterus position during early gestation. Scattered radiation was attenuated 13% and 21% with 2% barium sulfate and 87% and 96% with 40% barium sulfate, as calculated in the near and far fields, respectively, and 99% with the 1-mm lead sheet. The extrapolated attenuations for 5%-40% barium sulfate suspensions indicated that beyond a 30% suspension, attenuation increased further only slightly. CONCLUSION: Study results in the phantom experiment suggest that fetal irradiation during maternal chest CT can be reduced substantially with barium shielding.

Anticipation of radiation dose to the conceptus from occupational exposure of pregnant staff during fluoroscopically guided electrophysiological procedures.

UNLABELLED: Conceptus dose from occupational exposure. INTRODUCTION: A female employee working in the electrophysiology suite has the right to know potential radiation hazards to the unborn child before she is pregnant or before she decides to formally declare her pregnancy. Moreover, the employer of a declared pregnant worker must evaluate the work situation and ensure that the conceptus dose is kept below the maximum permissible level during the remaining gestation period. The aim of this study was to develop a method for conceptus dose anticipation and determination of maximum workload allowed for the pregnant employee who participates in fluoroscopically guided electrophysiological procedures. METHODS AND RESULTS: A C-arm fluoroscopy system, an anthropomorphic phantom, and a radiation meter were used to obtain scattered air kerma dose rates separately for each of the three fluoroscopic projections typically used in the electrophysiology suite. Air kerma to conceptus dose conversion factors for all trimesters of gestation were calculated using Monte Carlo simulation. A formula is presented for the anticipation of the conceptus dose from occupational exposure of pregnant staff during fluoroscopically guided electrophysiological procedures. Normalized data are provided for conceptus dose estimation from occupational exposure of pregnant staff working in any electrophysiology laboratory. A methodology for estimation of maximum workload allowed for each month of the remaining gestation period of a worker who declared her pregnancy is proposed, which ensures that the regulatory dose limits are not exceeded. CONCLUSION: Data presented may be used for the implementation of a radiation protection program designed for pregnant staff working in an electrophysiological suite.

Radiological protection for diagnostic examination of pregnant women.

Application of diagnostic X-ray examination to pregnant women is complicated since risks to both mother and embryo/fetus must be considered. Embryos and fetuses are more sensitive to radiation than adults or children. The threshold doses for fetal death, malformations and mental retardation which are deterministic effects, are reported to be 100-200 mGy or higher. The relative risk for childhood cancer due to radiation at an absorbed dose of 10 mGy during embryonic/fetal development has been estimated at 1.4. However, the absorbed dose of the embryo/fetus during X-ray diagnostic examination in which the X-ray beam does not irradiate the embryo/fetus directly such as maternal skull and chest X-ray is extremely low, less than 0.01 mGy. Thus these diagnostic procedures are not a problem from the perspective of radiological protection of the embryo/fetus. However, for pelvic CT scan and barium enema in which the uterus is directly within the X-ray beam, the absorbed doses to the embryo/fetus are about 20-80 mGy and 10-20 mGy, respectively. Therefore, medical staff must pay careful attention to the embryo/fetus in application of these examinations. Pregnant women who were not aware of pregnancy at the time of their diagnostic exposure have great anxiety about radiation from such X-ray examinations. However, fetal doses below 100 mGy should not be considered a reason for terminating a pregnancy.

Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis.

PURPOSE: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate. MATERIALS AND METHODS: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. RESULTS: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2 Gy y-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. CONCLUSION: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates.

Pregnancy testing before high-dose radioiodine treatment: a case report.

This case emphasizes that negative urine pregnancy testing and a written declaration of the patient are not sufficient to safely exclude an early pregnancy. Serum pregnancy testing inherently has a diagnostic gap of about 1 wk following conception. We recommend sufficient contraception at least 1 mo before radioiodine treatment in women of childbearing age.

Fetal dose estimates and the ICRP abdominal dose limit for occupational exposure of pregnant staff to technetium-99m and iodine-131 patients.

The International Commission on Radiological Protection has recently recommended a supplementary dose limit of 2 mSv to the abdominal surface of a pregnant member of staff in order to provide protection to her fetus comparable to that in members of the public, whose annual limit is recommended to be 1 mSv. In order to determine whether this apparent attenuation factor of 50% is appropriate for nursing and imaging staff exposed to nuclear medicine patients, estimates were made of the ratios of the maternal abdominal surface to fetal dose appropriately weighted for time, distance and dose rate. Thermoluminescent dosimeter (TLD) measurements were made at various depths in an anthropomorphic phantom irradiated at different distances by a distributed source of either technetium-99m or iodine-131 in order to determine the corresponding attenuation factors at the average fetal midline depth. Dose estimates were based on these factors and on published values of dose rate and exposure times for nursing and imaging staff at these distances from the patient. Fetal doses to nursing staff caring for an adult 99mTc patient were estimated to vary from 86 microSv to 1.6 microSv, with the corresponding ratio of the abdominal surface to fetal dose varying from about 1.8:1 to 1.5:1 as the patient became less dependent on nursing care and the mean distance from the patient increased. Fetal doses to imaging staff varied from 1.12 microSv to 0.17 microSv for three types of 99mTc scan, but the ratio only varied from 1.4:1 to 1.3:1. Fetal doses to imaging staff were estimated to be 6.7 microSv and 9.0 microSv for a whole-body scan of a thyroid cancer patient after 131I ablation and therapy respectively, and the ratio was 1.3:1 for both types of scan. It was concluded that for a pregnant ward nurse or imaging technologist exposed to an adult or paediatric patient administered 99mTc or 131I, a dose limit of 1.3 mSv to the maternal abdominal surface will restrict their fetal dose to 1 mSv. A pregnant imaging technologist should perform no more than six adult 99mTc studies or one 131I whole-body scan per day, and may have to wear a more sensitive personal dosimeter than a film badge.

Medical and drug risk factors associated with neuroblastoma: a case-control study.

A matched case-control study of prenatal risk factors for neuroblastoma was conducted, including 104 cases diagnosed over the period 1970-79 in the Greater Delaware Valley. Significantly elevated odds ratios (ORs) were associated with maternal use of a neurally active drug during pregnancy (OR = 2.83), sex hormone exposure 3 months prior to or during pregnancy (OR = 2.25), frequent alcohol consumption during pregnancy (OR = 9.0), and maternal use of diuretic drugs during pregnancy (OR = 5.75). Significantly more case mothers than control mothers reported use of hair coloring products during pregnancy (OR = 3.0). No association was found between cigarette smoking, coffee consumption, or medical irradiation and case-control status.

Radiation risks for patients having X rays.

In addition to radiation from naturally occurring radioactive materials and cosmic rays, individuals in developed countries receive radiation doses to bone marrow and gonads from the medical diagnostic use of X rays. A brief discussion of radiation epidemiology shows that deleterious effects are low even when doses are high. The concept of "acceptable risk" is introduced to help evaluate the small, but still existent, risks of radiation dose. Examples of bone marrow and gonadal doses for representative X-ray examinations are presented along with the current best estimates, per unit of X-ray dose, of the induction of leukemia or of genetic harm. The risk to the patient from an examination can then be compared with the normal risk of mortality from leukemia or of the occurrence of genetic defects. The risk increase is found to be very low. The risks to unborn children from radiographic examinations are also discussed. The benefit to the patient from information obtained from the examination must be balanced against the small risks.