Eurados review of retrospective dosimetry techniques for internal exposures to ionising radiation and their applications.

This work presents an overview of the applications of retrospective dosimetry techniques in case of incorporation of radionuclides. The fact that internal exposures are characterized by a spatially inhomogeneous irradiation of the body, which is potentially prolonged over large periods and variable over time, is particularly problematic for biological and electron paramagnetic resonance (EPR) dosimetry methods when compared with external exposures. The paper gives initially specific information about internal dosimetry methods, the most common cytogenetic techniques used in biological dosimetry and EPR dosimetry applied to tooth enamel. Based on real-case scenarios, dose estimates obtained from bioassay data as well as with biological and/or EPR dosimetry are compared and critically discussed. In most of the scenarios presented, concomitant external exposures were responsible for the greater portion of the received dose. As no assay is available which can discriminate between radiation of different types and different LETs on the basis of the type of damage induced, it is not possible to infer from these studies specific conclusions valid for incorporated radionuclides alone. The biological dosimetry assays and EPR techniques proved to be most applicable in cases when the radionuclides are almost homogeneously distributed in the body. No compelling evidence was obtained in other cases of extremely inhomogeneous distribution. Retrospective dosimetry needs to be optimized and further developed in order to be able to deal with real exposure cases, where a mixture of both external and internal exposures will be encountered most of the times.

Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

Membrane filtration coupled with wet air oxidation for intensified treatment of biorefractory effluents.

This work aims to analyse the performances of a new hybrid process: membrane filtration to concentrate biorefractory wastewater before treatment by a hydrothermal process such as wet air oxidation. The aim is to obtain a complete discharge of the effluent in the environment. The three different synthetic wastewaters under study were pharmaceutical wastewater, grey wastewater and bilge wastewater. The results of the membrane filtration showed high retention rates as it could reach between 75% and 100% of total organic carbon retention, more than 99% of turbidity removal and more than 70% of hydrocarbon retention. Moreover, it was possible to achieve high concentration factors comprised between 17 and 40 times. Membrane fouling was chemically reversible regardless of the type of pollution. Then, the treatment of the membrane retentates by wet air oxidation process (300 °C, 15 MPa) could eliminate more than 83% of organic pollution for all the tested effluents. In summary, the hybrid intensified process could finally decrease the volume and the waste load of wastewater before possibly discharging it into the environment.

Measuring oxygen uptake in fishes with bimodal respiration.

Respirometry is a robust method for measurement of oxygen uptake as a proxy for metabolic rate in fishes, and how species with bimodal respiration might meet their demands from water v. air has interested researchers for over a century. The challenges of measuring oxygen uptake from both water and air, preferably simultaneously, have been addressed in a variety of ways, which are briefly reviewed. These methods are not well-suited for the long-term measurements necessary to be certain of obtaining undisturbed patterns of respiratory partitioning, for example, to estimate traits such as standard metabolic rate. Such measurements require automated intermittent-closed respirometry that, for bimodal fishes, has only recently been developed. This paper describes two approaches in enough detail to be replicated by the interested researcher. These methods are for static respirometry. Measuring oxygen uptake by bimodal fishes during exercise poses specific challenges, which are described to aid the reader in designing experiments. The respiratory physiology and behaviour of air-breathing fishes is very complex and can easily be influenced by experimental conditions, and some general considerations are listed to facilitate the design of experiments. Air breathing is believed to have evolved in response to aquatic hypoxia and, probably, associated hypercapnia. The review ends by considering what realistic hypercapnia is, how hypercapnic tropical waters can become and how this might influence bimodal animals' gas exchange.

Increased temperature tolerance of the air-breathing Asian swamp eel Monopterus albus after high-temperature acclimation is not explained by improved cardiorespiratory performance.

This study investigated the hypothesis that in the Asian swamp eel Monopterus albus, an air-breathing fish from south-east Asia that uses the buccopharyngeal cavity for oxygen uptake, the upper critical temperature (TU) is increased by acclimation to higher temperature, and that the increased TU is associated with improved cardiovascular and respiratory function. Monopterus albus were therefore acclimated to 27° C (current average) and 32° C (current maximum temperature as well as projected average within 100-200 years), and both the effect of acclimation and acute temperature increments on cardiovascular and respiratory functions were investigated. Two weeks of heat acclimation increased upper tolerated temperature (TU ) by 2° C from 36·9 ± 0·1° C to 38·9 ± 0·1° C (mean ± s.e.). Oxygen uptake (M˙O2) increased with acclimation temperature, accommodated by increases in both aerial and aquatic respiration. Overall, M˙O2 from air (M˙O2a ) was predominant, representing 85% in 27° C acclimated fish and 80% in 32° C acclimated fish. M˙O2 increased with acute increments in temperature and this increase was entirely accommodated by an increase in air-breathing frequency and M˙O2a . Monopterus albus failed to upregulate stroke volume; rather, cardiac output was maintained through increased heart rate with rising temperature. Overall, acclimation of M. albus to 32° C did not improve its cardiovascular and respiratory performance at higher temperatures, and cardiovascular adaptations, therefore, do not appear to contribute to the observed increase in TU.

Swimming in air-breathing fishes.

Fishes with bimodal respiration differ in the extent of their reliance on air breathing to support aerobic metabolism, which is reflected in their lifestyles and ecologies. Many freshwater species undertake seasonal and reproductive migrations that presumably involve sustained aerobic exercise. In the six species studied to date, aerobic exercise in swim flumes stimulated air-breathing behaviour, and there is evidence that surfacing frequency and oxygen uptake from air show an exponential increase with increasing swimming speed. In some species, this was associated with an increase in the proportion of aerobic metabolism met by aerial respiration, while in others the proportion remained relatively constant. The ecological significance of anaerobic swimming activities, such as sprinting and fast-start manoeuvres during predator-prey interactions, has been little studied in air-breathing fishes. Some species practise air breathing during recovery itself, while others prefer to increase aquatic respiration, possibly to promote branchial ion exchange to restore acid-base balance, and to remain quiescent and avoid being visible to predators. Overall, the diversity of air-breathing fishes is reflected in their swimming physiology as well, and further research is needed to increase the understanding of the differences and the mechanisms through which air breathing is controlled and used during exercise.

Air-breathing fishes in aquaculture. What can we learn from physiology?

During the past decade, the culture of air-breathing fish species has increased dramatically and is now a significant global source of protein for human consumption. This development has generated a need for specific information on how to maximize growth and minimize the environmental effect of culture systems. Here, the existing data on metabolism in air-breathing fishes are reviewed, with the aim of shedding new light on the oxygen requirements of air-breathing fishes in aquaculture, reaching the conclusion that aquatic oxygenation is much more important than previously assumed. In addition, the possible effects on growth of the recurrent exposure to deep hypoxia and associated elevated concentrations of carbon dioxide, ammonia and nitrite, that occurs in the culture ponds used for air-breathing fishes, are discussed. Where data on air-breathing fishes are simply lacking, data for a few water-breathing species will be reviewed, to put the physiological effects into a growth perspective. It is argued that an understanding of air-breathing fishes' respiratory physiology, including metabolic rate, partitioning of oxygen uptake from air and water in facultative air breathers, the critical oxygen tension, can provide important input for the optimization of culture practices. Given the growing importance of air breathers in aquaculture production, there is an urgent need for further data on these issues.

[Comparative study of Vitek-2™ AIX versus Vitek-2™ PC: phenotypic resistance of enterobacteriaceae to ß-lactams]. / Comparaison du Vitek-2™ AIX versus Vitek-2™ PC par l'étude des phénotypes de résistance des entérobactéries aux ß-lactamines.

AIM OF THE STUDY: Vitek-2™ AIX versus Vitek-2™ PC have different rules for phenotypic interpretation. The aim of this study is to ensure that the raw results determined by these two versions of Vitek-2™ allow biologists to conclude to the same resistance phenotype, but also to evaluate their own phenotypic interpretation system (advanced expert system). MATERIAL AND METHODS: A total of 251 strains of Enterobacteriaceae of different groups and phenotypes was tested. Each strain was studied simultaneously on both types of Vitek-2™ from the same calibrated inoculum. We then compared their resistance phenotype to beta-lactams. RESULTS: For strains not producing ESBL or CHN, the biologist concluded in 99.3% of cases to the same resistance phenotype by interpreting the raw results of Vitek-2™ AIX versus PC. The phenotypic interpretation of biologist is different from the Vitek-2™ in respectively 40% versus 43% of cases for AIX and PC versions. For multi-resistant strains, the biologist concluded in 100% of cases to the same resistance phenotype by interpreting the raw results of Vitek-2™ AIX versus PC. In 51.5% of cases the biologist use the disk diffusion method (DD). The results of this technique put forward 29% discrepancy with the two types of Vitek-2™. Finally, when Vitek-2™ claims the presence of an ESBL alone, this result is routinely confirmed by DD. CONCLUSION: The switch from Vitek-2™ AIX to Vitek-2™ PC does not alter the results of the phenotypic interpretation of biologist.

Water and ion diffusion in partially-water saturated compacted kaolinite: Role played by vapor-phase diffusion in water mobility.

Diffusion is the main transport process of water and solutes in clay-rich porous media owing to their very low permeability, so they are widely used as barriers against contaminant spreading. However, the prediction of contaminant mobility can be very complicated when these media are partially water-saturated. We conducted diffusion experiments for water (HTO and HDO) and ions (22Na+ and 125I-) through partially water saturated compacted kaolinite, a weakly charged clay material, to quantify the distinct diffusive behavior of these species. The osmosis method was used to set kaolinite samples at 67, 86 and 100% saturation. The results showed that desaturation led to a sharp decrease in diffusive rates by factors of 6.5, 18 and 35 for HTO, 125I- and 22Na+, respectively, from 100 to 67% of the degree of saturation. Thus, to interpret water diffusivities, we proposed a model taking into account the diffusion of water in both gas and liquid phases, using diffusion data obtained for ions, considered as inert species. This model was capable of properly predicting water diffusive flux, especially at a low degree of saturation (67% saturation), for which the assumption made for the occurrence of air phase continuity throughout the sample appears to be more relevant than at 86% saturation.

[Immunofluorescence]. / Immunfluoreszenz.

The existence of autoantibodies is characteristic of several rheumatic diseases and indicates impaired self-tolerance. The analysis and detection of these autoantibodies represent an important factor in the diagnosis of rheumatic diseases. Immunofluorescence is an important technique in basic science and also one of the most commonly used techniques for the characterization of autoantibodies in clinical medicine thus facilitating the diagnosis and evaluation of rheumatic diseases. Addition of serum samples from individual patients to an antigen substrate (present in fixed cells or tissue) results in a specific reaction between the autoantibodies and the respective antigens. Incubation with a second, fluorescence-linked, anti-human antibody which binds to the primary antigen-bound autoantibodies from patient serum results in fluorescence patterns which are characteristic of certain rheumatic diseases.

[The allergist facing the COVID-19 pandemic: What impact and what precautions should be taken?] / L'allergologue face à l'épidémie de COVID-19 : quel impact et quelles précautions prendre ?

In the unusual health environment of the COVID 19 pandemic, allergists must adapt their exercise and their office or clinic, by strengthening hygiene and distancing precautions. In case of sanitary containment telehealth can, in many cases, replace face-to-face visits. Nevertheless, each practitioner must define the contingency planning and the priorities according to his own practice and the epidemic context.

The therapeutic use of osmotic minipumps in the severe combined immunodeficiency (SCID) mouse model for rheumatoid arthritis.

OBJECTIVES: The viral gene transfer of interleukin 1 receptor antagonist (IL1ra) and interleukin 10 (IL10) into rheumatoid arthritis (RA) synovial fibroblasts (RASFs) has shown protective effects on cartilage destruction in the severe combined immunodeficiency (SCID) mouse model of RA. Nevertheless, side effects of viral transduction are possible and a number of cytokines or cytokine inhibitors are not available encoded in viral vehicles. As the production of viruses coding for bioactive proteins is cost and time intensive, we established an in vivo long-term release model using osmotic minipumps in the SCID mouse model for RA. METHODS: Isolated RASFs were cultured for four passages and coimplanted together with human cartilage and an Alzet osmotic miniature pump model 2004, containing 200 microl of IL10 and IL1ra for 40 days in SCID mice. Implants were removed after 40 days and evaluated histologically. The actual rates of IL10 and IL1ra in murine serum were measured by ELISA. RESULTS: Release of IL10 and IL1ra by the pumps was effective as both could be measured in significant amounts in the serum of the mice. IL10 and IL1ra release showed protective effects towards the coimplanted cartilage, similar to the adenovirally IL10/IL1ra-transduced RASFs. The mean (SD) invasion scores for the implants with the osmotic pumps were: invasion 0.7 (0.5), degradation 0.5 (0.3) (all parameters significant vs controls, p<0.05). CONCLUSIONS: The results demonstrate that the combination of osmotic pumps with the SCID mouse model for RA can be used as approach for application and evaluation of cartilage-protective molecules. Furthermore, the effect of cartilage-protective cytokines is independent of the type of application.

Juvenile idiopathic arthritis and exposure to fine particulate air pollution.

OBJECTIVES: Inhalation of fine particulate matter, including particles with an aerodynamic diameter less than or equal to a 2.5-microm cut point (PM2.5), has been associated with systemic inflammation and the clinical presentation of various cardiopulmonary heath events. The urban area along Utah's Wasatch Mountains has high PM2.5 concentrations during periods of stagnant air conditions. Short-term inhalation exposures may trigger inflammatory events presenting as symptom onset in new patients with juvenile idiopathic arthritis (JIA). This study evaluated potential associations between JIA symptom onset and temporal changes in regional air pollution measured by stagnant air conditions and PM2.5 concentrations. METHODS: A case-crossover design was used to analyze associations of regional ambient PM2.5 concentrations with onset date of 338 JIA cases living on Utah's Wasatch Front. Patients were drawn from the Intermountain States Database of Childhood Rheumatic Diseases (1993-2006). Time trends, seasonality, month, and weekday were controlled for by matching. Selected exposure windows of PM2.5 and stagnant air days were used in the model to determine the effect of short term cumulative exposure on JIA symptom onset. RESULTS: Increased concentrations of PM2.5 and stagnant air conditions in the preceding 14 days were associated with significantly elevated risk of JIA onset in preschool aged children (RR=1.60, 95% CI 1.00-2.54) but not older children. Elevated risk was larger in males and in systemic onset JIA. CONCLUSION: Exposure to stagnant polluted air may be an environmental risk factor for JIA in young children, potentially triggered by pollution-induced pulmonary mediated inflammation.

Regulation of extracellular ATP of human erythrocytes treated with α-hemolysin. Effects of cell volume, morphology, rheology and hemolysis.

Alpha-hemolysin (HlyA) of uropathogenic strains of Escherichia coli irreversibly binds to human erythrocytes (RBCs) and triggers activation of ATP release and metabolic changes ultimately leading to hemolysis. We studied the regulation of extracellular ATP (ATPe) of RBCs exposed to HlyA. Luminometry was used to assess ATP release and ATPe hydrolysis, whereas changes in cell volume and morphology were determined by electrical impedance, ektacytometry and aggregometry. Exposure of RBCs to HlyA induced a strong increase of [ATPe] (3-36-fold) and hemolysis (1-44-fold), partially compensated by [ATPe] hydrolysis by ectoATPases and intracellular ATPases released by dead cells. Carbenoxolone, a pannexin 1 inhibitor, partially inhibited ATP release (43-67%). The un-acylated toxin ProHlyA and the deletion analog HlyA∆914-936 were unable to induce ATP release or hemolysis. For HlyA treated RBCs, a data driven mathematical model showed that simultaneous lytic and non-lytic release mainly governed ATPe kinetics, while ATPe hydrolysis became important after prolonged toxin exposure. HlyA induced a 1.5-fold swelling, while blocking this swelling reduced ATP release by 77%. Blocking ATPe activation of purinergic P2X receptors reduced swelling by 60-80%. HlyA-RBCs showed an acute 1.3-2.2-fold increase of Ca2+i, increased crenation and externalization of phosphatidylserine. Perfusion of HlyA-RBCs through adhesion platforms showed strong adhesion to activated HMEC cells, followed by rapid detachment. HlyA exposed RBCs exhibited increased sphericity under osmotic stress, reduced elongation under shear stress, and very low aggregation in viscous media. Overall results showed that HlyA-RBCs displayed activated ATP release, high but weak adhesivity, low deformability and aggregability and high sphericity.

How mobile is tritiated water through unsaturated cement-based materials? New insights from two complementary approaches.

This work presents two complementary approaches (for low and high desaturation) to study tritiated water (HTO) diffusion through unsaturated cement-based materials. The first approach was based on through-diffusion experiments where suction was controlled by osmosis. In the second approach, diffusion experiments were performed in humidity chambers controlled by under-saturated saline solutions. Results revealed a decrease of effective diffusion coefficient by a factor of 10 from 100% to 23% of saturation degree. Comparison with gaseous H2 suggests that HTO diffuses through unsaturated cement-based materials at rates 4 orders of magnitude lower.

Monitoring translocations by M-FISH and three-color FISH painting techniques: a study of two radiotherapy patients.

PURPOSE: To compare translocation rate using either M-FISH or FISH-3 in two patients treated for head and neck cancer, with a view to retrospective dosimetry. MATERIALS AND METHODS: Translocation analysis was performed on peripheral blood lymphocyte cultures from blood samples taken at different times during the radiotherapy (0 Gy, 12 Gy and 50 Gy) and a few months after the end of the treatment (follow-up). RESULTS: Estimated translocation yield varied according to the FISH technique used. At 50 Gy and follow-up points, the translocation yields were higher with FISH-3 than with M-FISH. This difference can be attributed to three events. First, an increase in complex aberrations was observed for 50 Gy and follow-up points compared with 0 Gy and 12 Gy points. Second, at the end of treatment for patient A, involvement of chromosomes 2, 4, 12 in translocations was less than expected according to the Lucas formula. Third, a clone bearing a translocation involving a FISH-3 painted chromosome was detected. CONCLUSIONS: More translocations were detected with M-FISH than with FISH-3, and so M-FISH is expected to improve the accuracy of chromosome aberration analyses in some situations.

TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood.

After invading red blood cells (RBCs), Plasmodium falciparum (Pf) can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel (VDAC). Moreover, ligands of the VDAC partner TranSlocator PrOtein (TSPO) were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX (ZnPPIX) and enhancing the accumulation of reactive oxygen species (ROS). TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2-VDAC complex, which leads to an accumulation of ROS.

Genome instability in secondary solid tumors developing after radiotherapy of bilateral retinoblastoma.

Genome alterations of seven secondary tumors (five osteosarcomas, one malignant peripheral sheath nerve tumor, one leiomyosarcoma) occurring in the field of irradiation of patients treated for bilateral retinoblastoma have been studied. These patients were predisposed to develop radiation-induced tumors because of the presence of a germ line mutation in the retinoblastoma gene (RB1). Tumor cells were characterized by a high chromosome instability whereas microsatellites and minisatellites were found to be stable. In all tumors, the normal RB1 allele was lost with the corresponding chromosome 13, whereas the germ line mutated allele was retained. The two alleles of TP53 were inactivated, one by deletion of the short arm of chromosome 17, the other by mutation. As compared with non-radiation-induced tumors, the observed panel of TP53 mutations was uncommon with sites not recurrently found otherwise and a high rate of deletions (3/7). In these predisposed patients, the loss of the single normal allele of RB1 is rather due to the radiation-induced chromosome instability than a direct effect of ionizing radiation.