Analysis of EURADOS neutron intercomparison results according to new ISO standards criteria.

The European Radiation Dosimetry Group has carried out several different types of intercomparison (IC) exercises in the past that qualify as proficiency tests for different dosimetry systems and types of radiation. The first neutron dosemeter IC was held in 2012 (IC2012n) and was followed by a second in 2017/2018 (IC2017n). In sum, 31 Individual Monitoring Services (IMSs) entered 34 dosimetry systems in IC2012n, and 32 IMSs entered 33 dosimetry systems for IC2017n. Such exercises provided a rare opportunity to see how neutron dosemeters perform. For the IC2012n exercise, there were no applicable performance standards for neutron personal dosemeters. ISO/TC85/SC2 updated the ISO Standard 14146 in 2018 (ISO 14146:2018. Radiation protection-Criteria and performance limits for the periodic evaluation of dosimetry services) to include neutron dosimetry. It was thus possible to analyse the IC2017n exercise in accordance with the requirements given by this new standard. It is now of interest to reanalyse the results of IC2012n to quantify any modifications to the conclusions.

Acute responses of hepatic fat content to consuming fat, glucose and fructose alone and in combination in non-obese non-diabetic individuals with non-alcoholic fatty liver disease.

We have recently demonstrated that a high-fat load can induce immediate increase in hepatic fat content (HFC) and that such an effect can be modified differently by co-administration of fructose or glucose in healthy subjects. Therefore, we addressed the question how consumption of these nutrients affects changes in HFC in subjects with non-alcoholic fatty liver disease (NAFLD). Eight male non-obese non-diabetic patients with NAFLD underwent 6 experiments each lasting 8 hours: 1. fasting, 2. high-fat load (150 g of fat (dairy cream) at time 0), 3. glucose (three doses of 50 g at 0, 2, and 4 hours), 4. high-fat load with three doses of 50 g of glucose, 5. fructose (three doses of 50 g at 0, 2, and 4 hours), 6. high-fat load with three doses of 50 g of fructose. HFC was measured using magnetic resonance spectroscopy prior to meal administration and 3 and 6 hours later. Plasma triglycerides, non-esterified fatty acids, glucose and insulin were monitored throughout each experiment. HFC increased by 10.4 ± 6.9% six hours after a high-fat load and by 15.2 ± 12.5% after high-fat load with fructose. When co-administering glucose with fat, HFC rose only transiently to return to baseline at 6 hours. Importantly, NAFLD subjects accumulated almost five times more fat in their livers than healthy subjects with normal HFC. Consumption of a high-fat load results in fat accumulation in the liver of NAFLD patients. Fat accumulation after a fat load is diminished by glucose but not fructose co-administration.

CHARACTERISATION OF RADIOPHOTOLUMINESCENCE DOSIMETRY SYSTEM FOR INDIVIDUAL MONITORING.

Performance evaluation is typically assessed as part of the approval procedure to verify that a dosimetry system fulfils specified national or international type-test requirements under representative exposure conditions that are expected to mimic workplace fields from the radiological activities being monitored. The International Atomic Energy Agency Radiation Safety Technical Services Laboratory has recently implemented an integrated radiophotoluminescence (RPL) personal dosimetry system developed by Chiyoda Technol Corporation. This paper reports on the successful verification of dosimetric performance properties of the RPL dosimetry system to IEC 62387:2020, in which the badges were exposed to a range of radiation energies and angles of incidence as well as other influence parameters. Characteristics under test included the coefficient of variation, non-linearity of response due to dose dependence as well as the energy and angular response to photon and beta radiation.

Determination of antimicrobial activity of Achatina reticulata slime.

BACKGROUNDS: Snails (Gastropoda) have a mechanism for the production of a significant amount of slime and substances contained therein they use to protect themselves against bacterial or fungal pathogens. These active substances are involved in both humoral and cellular immune responses of the gastropods. The antibacterial or antifungal effect of the humoral immune component of slime lies in cytotoxic and haemagglutination activity against potential microbial pathogens. The activity of antibacterial agents present in Achatina reticulata slime against bacterial strains of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa was tested. MATERIAL AND METHODS: A total of five samples of slime from laboratory reared Achatina reticulata were tested. To eliminate potential microbial contamination, slime samples were sterilized by UV radiation. To screen slime samples for antibacterial activity, the simple diffusion method on Mueller-Hinton agar was used. Samples diluted in guaiacol glycerol ether were used in the testing. RESULTS: The results show that the biologically active substances present in Achatina reticulata slime have an antimicrobial activity which is almost commensurate with that of the conventional antibiotics used to treat bacterial infections. The results of the determination of the antimicrobial effects of Achatina reticulata slime also highlighted viridation (partial hemolysis of erythrocytes after 24 hours of slime cultivation exposed to UV light for 60 minutes on Columbia blood agar. CONCLUSIONS: The results of the antimicrobial activity testing of selected Achatina reticulata slime samples show that the gastropod slime contains biologically active substances with a relatively significant antimicrobial activity.

Clinical and (31)P magnetic resonance spectroscopy characterization of patients with critical limb ischemia before and after autologous cell therapy.

Autologous cell therapy (ACT) is a new treatment method for diabetic patients with critical limb ischemia (CLI) not eligible for standard revascularization. After intramuscular injection of bone marrow-derived mononuclear cells local arteriogenesis in the ischemic tissue occurs. Studies assessing visualization of this therapeutic vasculogenesis after ACT by novel imaging techniques are lacking. The aim of our study was to assess the effect of ACT on possible metabolic changes and perfusion of critically ischemic limbs using (31)P magnetic resonance spectroscopy ( (31)P MRS) and its possible correlation with changes of transcutaneous oxygen pressure (TcPO(2)). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO(2) as well as rest (phosphocreatine, adenosine triphosphate and inorganic phosphate) and dynamic (mitochondrial capacity and phosphocreatine recovery time) (31)P-MRS parameters were evaluated at baseline and 3 months after cell treatment. TcPO(2) increased significantly after 3 months compared with baseline (from 22.4±8.2 to 37.6±13.3 mm Hg, p=0.0002). Rest and dynamic (31)P MRS parameters were not significantly different after ACT in comparison with baseline values. Our study showed a significant increase of TcPO(2) on the dorsum of the foot after ACT. We did not observe any changes of rest or dynamic (31)P MRS parameters in the area of the proximal calf where the cell suspension has been injected into.

A Trimodal Imaging Platform for Tracking Viable Transplanted Pancreatic Islets In Vivo: F-19 MR, Fluorescence, and Bioluminescence Imaging.

PURPOSE: Combining specific and quantitative F-19 magnetic resonance imaging (MRI) with sensitive and convenient optical imaging provides complementary information about the distribution and viability of transplanted pancreatic islet grafts. In this study, pancreatic islets (PIs) were labeled with positively charged multimodal nanoparticles based on poly(lactic-co-glycolic acid) (PLGA-NPs) with encapsulated perfluoro-15-crown-5-ether and the near-infrared fluorescent dye indocyanine green. PROCEDURES: One thousand and three thousand bioluminescent PIs were transplanted into subcutaneous artificial scaffolds, which served as an alternative transplant site. The grafts were monitored using in vivo F-19 MR, fluorescence, and bioluminescence imaging in healthy rats for 2 weeks. RESULTS: Transplanted PIs were unambiguously localized in the scaffolds by F-19 MRI throughout the whole experiment. Fluorescence was detected in the first 4 days after transplantation only. Importantly, in vivo bioluminescence correlated with the F-19 MRI signal. CONCLUSIONS: We developed a trimodal imaging platform for in vivo examination of transplanted PIs. Fluorescence imaging revealed instability of the fluorescent dye and its limited applicability for longitudinal in vivo studies. A correlation between the bioluminescence signal and the F-19 MRI signal indicated the fast clearance of PLGA-NPs from the transplantation site after cell death, which addresses a major issue with intracellular imaging labels. Therefore, the proposed PLGA-NP platform is reliable for reflecting the status of transplanted PIs in vivo.

Differences in muscle metabolism in patients with type I diabetes - influence of gender and nephropathy studied by (31)P MR spectroscopy.

Type I diabetes mellitus (DM1) is a complex disease with adverse effects on organs and tissues despite compensation by insulin treatment. The goal of our study was to study how kidney diseases change (31)P MR parameters of muscle metabolism in DM1 patients with respect to gender. 51 DM1 patients (19 m/14 f without and 13 m/5 f with nephropathy) and 26 (14 m/12 f) healthy volunteers were examined using (31)P magnetic resonance spectroscopy at 3T tomograph at rest, and during and after a calf muscle exercise. The exercise consisted of a six-minute plantar flexion using a pedal ergometer followed by a six-minute recovery. It is reflected by reduced relative beta-ATP and increased Pi and phosphodiester signals to phosphocreatine (PCr) at rest and prolongation of the PCr recovery time after the exercise. Measurement on healthy volunteers indicated differences between males and females in pH at the rest and after the exercise only. These differences between patients groups were not significant. We have proven that nephropathy affects the metabolism in diabetic patients and our results confirm significant difference between patients with and without nephropathy. Gender differences in pH were observed only between male and female healthy volunteers.

Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner.

Chemotherapy and radiation, the two most common cancer therapies, exert their anticancer effects by causing damage to cellular DNA. However, systemic treatment damages DNA not only in cancer, but also in healthy cells, resulting in the progression of serious side effects and limiting efficacy of the treatment. Interestingly, in response to DNA damage, p53 seems to play an opposite role in normal and in the majority of cancer cells-wild-type p53 mediates apoptosis in healthy tissues, attributing to the side effects, whereas mutant p53 often is responsible for acquired cancer resistance to the treatment. Here, we show that leucine zipper-containing ARF-binding protein (LZAP) binds and stabilizes p53. LZAP depletion eliminates p53 protein independently of its mutation status, subsequently protecting wild-type p53 cells from DNA damage-induced cell death, while rendering cells expressing mutant p53 more sensitive to the treatment. In human non-small-cell lung cancer, LZAP levels correlated with p53 levels, suggesting that loss of LZAP may represent a novel mechanism of p53 inactivation in human cancer. Our studies establish LZAP as a p53 regulator and p53-dependent determinative of cell fate in response to DNA damaging treatment.

GABA spectra and remote distractor effect in progressive supranuclear palsy: A pilot study.

Disturbances of the gamma-aminobutyric-acid (GABA) system have been suspected of contributing to the pathophysiology of progressive supranuclear palsy (PSP). The ability to rapidly resolve competitive action decisions, such as shifting the gaze to one particular stimulus rather than another, can be predicted by the concentration of GABA in the region of the frontal cortex relevant to eye movements. For this reason, our study measured GABA levels in seven PSP patients and eight healthy controls, using proton magnetic resonance spectroscopy, and assessed the relationship of these measurements to the remote distractor effect (RDE), an eye-movement paradigm investigating competitive action decisions. No significant differences were found in either frontal-eye-field GABA levels or RDE between PSP patients and controls.

[Flow cytometry in microbiology]. / Prutoková cytometrie v mikrobiologii.

Flow cytometry is a method that allows simultaneous measurement and analysis of physical and chemical characteristics of cells or other biological particles during their passage through the laser beam. Although this method is mainly used in the study of cell differentiation and functional analysis of eukaryotic cells, the basic principles of flow cytometry can be applied to microorganisms. Methods based on the analysis of a single cell, such as flow cytometry, in combination with measurement of cell viability using special fluorescent probes allow a deeper insight into the diversity of populations and functioning of microbial communities and also facilitate understanding the phy-siological diversity of seemingly similar acting populations. When using specific fluorescent dyes for the selective labeling of selected species of microorganisms, the method is potentially very specific. The aim of this paper is a brief overview of applications of flow cytometry, which can be used in microbiology.

[The effect of oxygen on endotoxin production in bacteria of the Bacteroides fragilis group isolated from patients with colorectal carcinoma]. / Vliv kyslíku na produkci endotoxinu u bakterií ze skupiny Bacteroides fragilis group izolovaných od pacientu s kolorektálním karcinomem.

OBJECTIVE: The aim of the study was to draw attention to the risk posed by anaerobic bacteria of the Bacteroides fragilis (BAFR) group, isolated particularly from abdominal lesions, and to assess the possible role of these species in colorectal cancer. A correlation has previously been suggested between the detection of the bacteria of the genus Bacteroides in patients on a meat-based diet and intestinal and, in particular, colorectal cancer. Given that the species of the BAFR group are major producers of endotoxins, measurements and statistical analysis of endotoxin production were used to compare the Bacteroides strains isolated from clinical specimens of patients with colon cancer, rectal cancer, and other abdominal lesions. MATERIALS AND METHODS: Endotoxin production was detected in bacterial strains of the BAFR group (B. fragilis, B. thetaiotaomicron, B. distasonis, and B. vulgatus) isolated from clinical specimens of patients with rectal cancer, colon cancer, and intestinal cancer and was compared with that in strains from samples of patients with inflammatory conditions (anal abscess, appendicitis, skin abscess, etc.) under anaerobic and microaerophilic (with 5% of oxygen) culture conditions. The production of endotoxins was detected quantitatively using the Pyrosate LAL assay kit (Limulus Amoebocyte Lysate Test, BIOGENIX, CR) in four species of the BAFR group after anaerobic and microaerophilic culture. Five strains of each isolated Bacteroides species from each type of specimens were tested (in total 140 BAFR strains). The amount of endotoxin was given in endotoxin units per ml (EU/ml). RESULTS: Endotoxin production by bacteria under microaerophilic culture conditions was several times higher in comparison with strictly anaerobic culture.The difference was statistically significant (F1.269 = 160, p <0.0001). As regards the effect of oxygen on endotoxin production, the amount of endotoxins produced under microaerophilic culture conditions (average 889.1 EU/ml) was 2.5 times as high as that observed under anaerobic culture conditions (358.2 EU/ml), regardless of the bacteroides species and diagnosis. These results suggest that the amount of free oxygen in the environment affects the amount of endotoxin generated by the Bacteroides strains. CONCLUSION: The results show that endotoxin production by the Bacteroides strains under microaerophilic culture conditions is several times as high as that under strictly anaerobic culture conditions.

The age dependence of T2 relaxation times of N-acetyl aspartate, creatine and choline in the human brain at 3 and 4T.

Knowledge of the T2 age dependence is of importance for MRS clinical studies involving subject groups with a wide age range. A number of studies have focused on the age dependence of T2 values in the human brain, with rather conflicting results. The aim of this study was to analyze the age dependence of T2 values of N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho) in the human brain using data acquired at 3T and 4T and to assess the influence of the macromolecule (MM) baseline handling on the obtained results. Two distinct groups of young and elderly controls have been measured at 3T (TE = 30-540 ms, 9 young and 11 elderly subjects) and 4T (TE = 10-180 ms, 18 young and 14 elderly subjects) using single-voxel spectroscopy. In addition, MM spectra were measured from two subjects using the inversion-recovery technique at 4T. All spectra were processed with LCModel using basis sets with different MM signals (measured or simulated) and also with MM signals included for a different TE range. Individual estimated T2 values were statistically analyzed using the R programming language for the age dependence of T2 values as well as the influence of the MM baseline handling. A significant decrease of T2 values of NAA and Cr in elderly subjects compared with young subjects was confirmed. The same trend was observed for Cho. Significantly higher T2 values calculated using the measured MM baseline for all studied metabolites at 4T were observed for both young and elderly subjects. To conclude, while the handling of MM and lipid signals may have a significant effect on estimated T2 values, we confirmed the age dependence of T2 values of NAA and Cr and the same trend for Cho in the human brain. Copyright © 2016 John Wiley & Sons, Ltd.

A SOLUTION FOR NEUTRON PERSONAL DOSIMETRY IN THE ABSENCE OF WORKPLACE SPECTROMETRY.

In view of the widely varying energy spectra encountered in practical situations, accuracy of neutron dose assessment requires detailed knowledge of detector responses and workplace conditions to achieve an adequate level of protection. If the neutron spectrum should be a priori unknown and no measurement of the workplace spectrum is available, the 'Compendium of Neutron Spectra and Detector Responses for Radiation Protection Purposes' published in the International Atomic Energy Agency Technical Report Series offers a broad range of reference spectra that may be appropriate for many applications. The proposed approach applies a correction factor based on the ratio of 'personal dose equivalent indices' for a particular workplace spectrum and a reference field used for calibration of the dosemeter response. Amendments in the definition of operational quantities as well as introduction of new modalities that, for example, may be expected to give increased importance to high-energy neutrons necessitate frequent revision of the Compendium. Results from the European Radiation Dosimetry Group Intercomparison 2012 for neutron personal dosemeters provide evidence that workplace fields are insufficiently reflected. This is proposed to be considered as an improvement opportunity.

Minipig model of Huntington's disease: ¹H magnetic resonance spectroscopy of the brain.

Huntington's disease (HD) is an inherited autosomal neurodegenerative disorder affecting predominantly the brain, characterized by motor dysfunctions, behavioral and cognitive disturbances. The aim of this study was to determine changes in the brain of transgenic minipigs before HD onset using (1)H magnetic resonance (MR) spectroscopy. Measurements were performed on a 3 T MR scanner using a single voxel spectroscopy sequence for spectra acquisition in the white matter and chemical shift imaging sequence for measurement in the striatum, hippocampus and thalamus. A decrease of (phospho)creatine (tCr) concentration was found only in the thalamus (p=0.002) of transgenic minipigs, nevertheless we found significant changes in metabolite ratios. Increase of the ratio choline compounds (tCho)/tCr was found in all examined areas: striatum (p=0.010), thalamus (p=0.011) as well as hippocampus (p=0.027). The ratio N-acetylaspartate+N-acetylaspartylglutamate (tNAA)/tCr (p=0.043) and glutamate+glutamine (Glx)/tCr (p=0.039) was elevated in the thalamus, the ratio myo-inositol (Ins)/tCr (p=0.048) was significantly increased in the hippocampus. No significant differences were observed in the metabolite concentrations in the white matter, however we found significant increase of ratios tNAA/tCr (p=0.018) and tCho/tCr (p=0.003) ratios in transgenic boars. We suppose that the majority of the observed changes are predominantly related to changes in energy metabolism caused by decrease of tCr.

Influence of breathing on the measurement of lipids in the myocardium by ¹H MR spectroscopy.

The myocardium examination by MR spectroscopy is very challenging due to movements caused by the cardiac rhythm and breathing. The aim of the study was to investigate the influence of breathing on the quantitative measurement of lipid/water ratios in different groups of volunteers and different measuring protocols. We examined the lipid content of myocardium at 3T using the proton single voxel spectroscopy. Three protocols (free breathing, breath hold and the use of respiratory navigator) controlled by ECG were used for the examination of 42 adult volunteers including 14 free divers. Spectra were evaluated using jMRUI software. An average content of lipids in the healthy interventricular septum, gained by all protocols was equal to 0.6 %, which is in agreement with other published data. Based on the quality of examinations and the highest technical success, the best protocol seems to be the one containing a respiratory navigator since it is more acceptable by patients. Based on our results and the literature data we can conclude that MR spectroscopy is able to distinguish patients from controls only if their myocardial lipid content is higher than 1.6 % (mean value of lipids plus two standard deviations).

Developments and trends in bioequivalent dosimetry.

Significant progress in radiobiology has refined the understanding of radiation-induced biological response at the cellular level and challenged the conventional application of a macroscopic description of radiation action to dosimetry in favour of a microscopic approach. Pioneering experiments, which investigated the stochastics of energy deposition from ionising radiations in volumes of cellular dimensions, contributed to the recognition of microdosimetry as a new scientific discipline. The first quantitative applications of Monte Carlo track structure simulations in radiobiology, however, supported evidence for target sizes of particular biological importance being in the nanometre regime. Bioequivalent dosimetry attempts to link particular features of the response of physical detectors with biological endpoints, exploiting clusters of multiple ionisations within nanometre scales in solid-state, gas- and water-filled devices. This approach supports the continued development of new concepts and quantities in radiation protection to permit evaluation of the biological effectiveness of radiations of different quality independently of dose and dose rate.

The relationships between quantitative MR parameters in hippocampus in healthy subjects and patients with temporal lobe epilepsy.

We introduce a new magnetic resonance (MR) method based on a pixel-by-pixel image processing to examine relationships between metabolic and structural processes in the pathologic hippocampus. The method was tested for lateralization of the epileptogenic zone in patients with temporal lobe epilepsy (TLE). Twenty patients with drug-resistant TLE and fifteen healthy controls were examined at 3T. The measurement protocol contained T2-weighted MR images, spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Correlations between quantitative MR parameters were calculated on a pixel-by-pixel basis using the CORIMA program which enables automated pixel identification in the normal tissue according to control data. All MR parameters changed in the anteroposterior direction in the hippocampus and correlation patterns and their slopes differed between patients and controls. Combinations of T2 relaxation times with metabolite values represent the best biomarkers of the epileptogenic zone. Correlations with mean diffusivity did not provide sufficiently accurate results due to diffusion image distortions. Quantitative MR analysis non-invasively provides a detailed description of hippocampal pathology and may represent complementary tool to the standard clinical protocol. However, the automated processing should be carefully monitored in order to avoid possible errors caused by MR artifacts.

Effect of acute hyperinsulinemia on brain metabolism evaluated by 1H MR spectroscopy--a pilot study.

To determine whether acutely-induced supraphysiological hyperinsulinemia influences brain metabolism in patients with type 1 diabetes (D) and healthy controls (C) as detected by MR Spectroscopy. Group D consisted of 4 patients with the average duration of diabetes for 7 years. They were matched according to age, sex and BMI to 4 healthy controls. 1H MR Spectroscopy was performed with a 1.5 Tesla. Spectra were obtained from parietooccipital white matter repeatedly during a 3-h hyperinsulinemic euglycemic clamp with 2 mU.kg(-1).min(-1). In group D, significantly lower basal concentrations of N-acetylaspartate (p=0.02), choline (p=0.03), creatine (p=0.002) and inositol (p=0.007) were detected compared to C. After the induction of hyperinsulinemia, concentrations of choline, creatine, GABA, inositol, lactate, NAA and composite signal glutamate + glutamine (Glx) stayed stable. The detection of glucose signal is less realiable at 1.5 Tesla but we registered the alteration in glucose concentration (p=0.003) in the whole group. Originally sightly elevated glucose concentration in D decreased on the contrary to the increase of originally lower glucose level in C. In conclusions, brain metabolism was altered in D. Short term supraphysiological euglycemic hyperinsulinemia induced changes in the concentration of brain glucose in both C and D.