[Breast pain and fever in a 46-year-old immunosuppressed patient with breast implants]. / Schmerzen im Bereich der Mamma und Fieber bei einer 46­Jährigen mit Immunsuppression und Mammaaugmentation.

A 46-year-old immunosuppressed patient presented with a breast implant-associated infection 10 years after breast augmentation in Southeast Asia. No pathogen was identified in the initial conventional microbiological workup. Subsequently, infection with Mycobacterium abscessus-a nontuberculous mycobacteria-was diagnosed using a special culture technique. Increased rates of such infections are reported after cosmetic surgery in foreign countries, presumably due to inoculation with these ubiquitous pathogens. This case highlights the fact that the differential diagnosis and thus the microbiological workup should be extended in cases without initial pathogen detection.

Influence of chromatin compaction on simulated early radiation-induced DNA damage using Geant4-DNA.

PURPOSE: In this work, we present simulated double-strand breaks (DSBs) obtained for two human cell nucleus geometries. The first cell nucleus represents fibroblasts, filled with DNA molecules in different compaction forms: heterochromatin or euchromatin only. The second one represents an endothelial cell nucleus, either filled with heterochromatin only or with a uniform distribution of 48% of heterochromatin and 52% of euchromatin, obtained from measurements carried out at IRSN. Protons and alpha particles of different energies were used as projectiles. Each cell nucleus model includes a multi-scale description of the DNA target from the molecular level to the whole human genome representation. METHODS: The cell nucleus models were generated using an extended version of the DnaFabric software in which a new model of euchromatin was implemented in addition to the existing model of heterochromatin. Thus, each nucleus model contains the complete human genome (a total of 6 Gbp) in the G0/G1 phase of the cycle, filled with a continuous chromatin fiber per chromosome that can take into account the heterochromatin and the euchromatin compaction. These geometries were then exported to a simulation chain using the Monte Carlo toolkit Geant4-DNA to perform computations of the physical, physicochemical, and chemical stages, in order to evaluate the influence of chromatin compaction on DSB induction and the contribution of direct and indirect damage, as well as DSB complexity. RESULTS: More direct damage and less indirect damage were observed in the heterochromatin than in the euchromatin. Nevertheless, no difference in terms of DSB complexity was observed between those formed in the heterochromatin or the euchromatin models. Yields of DSB/Gy/Gbp show an increase when both heterochromatin and euchromatin models are taken into account, compared to when only heterochromatin is considered. CONCLUSIONS: The results presented indicate that the chromatin compaction decreases DNA damage generated by ionizing radiation and thus, DNA compaction should be considered for the simulation of DNA repair and other cellular outcomes.

Geant4-DNA example applications for track structure simulations in liquid water: A report from the Geant4-DNA Project.

This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path…). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4-DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4-DNA (the so-called "option4" and "option 6" sets) enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquid water, than the default set of models ("option 2") initially provided in Geant4-DNA. They also serve as reference applications for Geant4-DNA users interested in TS simulations.

Track structure modeling in liquid water: A review of the Geant4-DNA very low energy extension of the Geant4 Monte Carlo simulation toolkit.

Understanding the fundamental mechanisms involved in the induction of biological damage by ionizing radiation remains a major challenge of today's radiobiology research. The Monte Carlo simulation of physical, physicochemical and chemical processes involved may provide a powerful tool for the simulation of early damage induction. The Geant4-DNA extension of the general purpose Monte Carlo Geant4 simulation toolkit aims to provide the scientific community with an open source access platform for the mechanistic simulation of such early damage. This paper presents the most recent review of the Geant4-DNA extension, as available to Geant4 users since June 2015 (release 10.2 Beta). In particular, the review includes the description of new physical models for the description of electron elastic and inelastic interactions in liquid water, as well as new examples dedicated to the simulation of physicochemical and chemical stages of water radiolysis. Several implementations of geometrical models of biological targets are presented as well, and the list of Geant4-DNA examples is described.

Influence of the geometrical detail in the description of DNA and the scoring method of ionization clustering on nanodosimetric parameters of track structure: a Monte Carlo study using Geant4-DNA.

The aim of this study was to evaluate the influence of the geometrical detail of the DNA on nanodosimetric parameters of track structure induced by protons and alpha particles of different energies (LET values ranging from 1 to 162.5 keV µm-1) as calculated by Geant4-DNA Monte Carlo simulations.The first geometry considered consisted of a well-structured placement of a realistic description of the DNA double helix wrapped around cylindrical histones (GeomHist) forming a 18 kbp-long chromatin fiber. In the second geometry considered, the DNA was modeled as a total of 1800 ten bp-long homogeneous cylinders (2.3 nm diameter and 3.4 nm height) placed in random positions and orientations (GeomCyl). As for GeomHist, GeomCyl contained a DNA material equivalent to 18 kbp. Geant4-DNA track structure simulations were performed and ionizations were counted in the scoring volumes. For GeomCyl, clusters were defined as the number of ionizations (ν) scored in each 10 bp-long cylinder. For GeomHist, clusters of ionizations scored in the sugar-phosphate groups of the double-helix were revealed by the DBSCAN clustering algorithm according to a proximity criteria among ionizations separated by less than 10 bp. The topology of the ionization clusters formed using GeomHist and GeomCyl geometries were compared in terms of biologically relevant nanodosimetric quantities.The discontinuous modeling of the DNA for GeomCyl led to smaller cluster sizes than for GeomHist. The continuous modeling of the DNA molecule for GeomHist allowed the merging of ionization points by the DBSCAN algorithm giving rise to larger clusters, which were not detectable within the GeomCyl geometry. Mean cluster size (m1) was found to be of the order of 10% higher for GeomHist compared to GeomCyl for LET < 15 keV µm-1. For higher LETs, the difference increased with LET similarly for protons and alpha particles. Both geometries showed the same relationship between m1 and the cumulative relative frequency of clusters with v≥3 (f3) within statistical variations, independently of particle type. In order to obtain ionization cluster size distributions relevant for biological DNA lesions, the complex DNA geometry and a scoring method without fixed boundaries should be preferred to the simple cylindrical geometry with a fixed scoring volume.

Experimental evidence of early costs of reproduction in conspecific viviparous and oviparous lizards.

Reproduction entails costs, and disentangling the relative importance of each stage of the reproductive cycle may be important to assess the costs and benefits of different reproductive strategies. We studied the early costs of reproduction in oviparous and viviparous lizard females of the bimodal reproductive species Zootoca vivipara. Egg retention time in oviparous females is approximately one-third of the time in viviparous females. We compared the vitellogenesis and egg retention stages that are common to both reproductive modes. Precisely, we monitored the thermoregulatory behaviour, the weight gain and the immunocompetence of the females. Moreover, we injected an antigen in half of the females (immune challenge) to study the trade-offs between reproductive mode and immune performance and between different components of the immune system. Finally, we experimentally induced parturition in viviparous females at the time of egg laying in oviparous females. Oviparous and viviparous females did not show strong differences in response to the immune challenge. However, viviparous females spent more time thermoregulating while partially hidden and gained more weight than oviparous females. The greater weight gain indicates that the initial period of egg retention is less costly for viviparous than for oviparous females or that viviparous females are able to save and accumulate energy at this period. This energy may be used by viviparous females to cope with the subsequent costs of the last two-third of the gestation. Such an ability to compensate the higher costs of a longer egg retention period may account for the frequent evolution of viviparity in squamate reptiles.

Carotenoid-based coloration, oxidative stress and corticosterone in common lizards.

Environmental factors including stressors, health status and social context significantly affect carotenoid-based coloration. For instance, stressors may induce the diversion of carotenoids from pigmentation pathways, potentially explaining why stressed animals often exhibit reduced coloration. However, we recently showed that high blood corticosterone concentrations, which are part of the physiological stress response, are associated with increased redness of the belly in the common lizard (Lacerta vivipara). This result clearly contrasts with the findings of many studies of carotenoid-based coloration because corticosterone is believed to increase oxidative stress. Here, we examined whether these positive effects are influenced by differences in food availability. We tested the effect of high corticosterone levels on carotenoid-based coloration, antioxidant enzyme activity and oxidative damage in common lizards subject to low and high food availability. Food restriction abolished the carotenoid-based color enhancement when corticosterone concentrations in animals were high. We discuss how carotenoid-based color can honestly signal individual quality in this species and how the increased redness induced by corticosterone could be a terminal investment in an environment where long-term survival prospects are poor but not when immediate survival is endangered.

Food deprivation modifies corticosterone-dependent behavioural shifts in the common lizard.

Stressful events typically induce glucocorticoid production that suppresses unnecessary physiological and behavioural functions. The glucocorticoid production also temporally activates alternative behavioural and physiological pathways. These responses are generally adaptive changes to avoid the negative effects of stressors. However, under low food availability, these behavioural and physiological modifications might lead to energetic costs. We therefore predict that these responses should not be activated when there are energetic constraints (e.g., low food availability). We experimentally tested whether food deprivation modifies corticosterone-induced behavioural and physiological responses in captive male common lizards. We measured corticosterone-induced responses in terms of body mass, metabolic rate, activity level and basking behaviour. We found that corticosterone-induced various behavioural and physiological responses which were dependent on food availability. Well-fed lizards treated with corticosterone were active earlier, and increased their basking behaviour. These behavioural modifications did not occur in food-deprived lizards. This inactivation of stress-related behavioural changes probably allows the lizard to save energy.

Interplay of different NOM fouling mechanisms during ultrafiltration for drinking water production.

Ultrafiltration is an emerging technology for drinking water production, but a main challenge remains the lack of understanding about fouling. This paper investigates the impact of molecular interactions between different natural organic matter (NOM) compounds on ultrafiltration fouling mechanisms. We performed dead-end filtration experiments with individual and mixed humic acid and alginate (polysaccharide). Alginate showed detrimental, but mostly reversible, flux decline and high solute retention. Our results indicate that this was caused by pore blocking transformed into cake building and weak molecular foulant-membrane and foulant-foulant interactions. In the presence of calcium, aggravated fouling was observed, related to complexation of alginate and its subsequently induced gel formation. With humic acid, more severe irreversible fouling occurred due to humic acid adsorption. Minor adsorption of alginate onto the membrane was also observed, which probably caused the substantial irreversible flux decline. The fouling characteristics in the mixtures reflected a combination of the individual humic acid and alginate experiments and we conclude, that the individual fouling mechanisms mutually influence each other. A model elucidates this interplay of the individual fouling mechanisms via hydrophobic and electrostatic interactions. In our study such an interplay resulted in an alginate cake, or gel in the presence of calcium, which is relatively irreversibly adsorbed onto the membrane by humic acid associations. This study shows the importance of mutual influences between various foulants for improved understanding of fouling phenomena. Furthermore it shows that substances with a minor individual influence might have a large impact in mixed systems such as natural water.

Ontogenic sources of variation in sexual size dimorphism in a viviparous lizard.

To elucidate the developmental aspects of the evolution of sexual size dimorphism (SSD), an understanding of the sex-specific ontogeny of body size is critical. Here, we evaluate the relative importance of genetic and environmental determinants of SSD in juvenile common lizards (Lacerta vivipara). We examined the prenatal and post-natal effects of population density and habitat humidity on SSD, as well as the maternal effects of food availability, corticosterone level, humidity and heat regime during gestation. Analyses indicated strong prenatal and post-natal plasticity in body size per se and yielded three main results with respect to SSD. First, SSD in juvenile common lizards matches qualitatively the SSD observed in adults. Secondly, SSD was influenced by none of the prenatal factors investigated here, suggesting poor sex-biased maternal effects on offspring size. Thirdly, SSD was sensitive to post-natal habitat humidity, which positively affected growth rate more strongly in females than in males. Thus, natural variation in SSD in juvenile common lizards appears to be primarily determined by a combination of sex-biased genetic factors and post-natal conditions. We discuss the possibility that viviparity may constrain the evolution of sex-biased maternal effects on offspring size.

Experimental enhancement of corticosterone levels positively affects subsequent male survival.

Corticosterone is an important hormone of the stress response that regulates physiological processes and modifies animal behavior. While it positively acts on locomotor activity, it may negatively affect reproduction and social activity. This suggests that corticosterone may promote behaviors that increase survival at the cost of reproduction. In this study, we experimentally investigate the link between corticosterone levels and survival in adult common lizards (Lacerta vivipara) by comparing corticosterone-treated with placebo-treated lizards. We experimentally show that corticosterone enhances energy expenditure, daily activity, food intake, and it modifies the behavioral time budget. Enhanced appetite of corticosterone-treated individuals compensated for increased energy expenditure and corticosterone-treated males showed increased survival. This suggests that corticosterone may promote behaviors that reduce stress and it shows that corticosterone per se does not reduce but directly or indirectly increases longer-term survival. This suggests that the production of corticosterone as a response to a stressor may be an adaptive mechanism that even controls survival.

The effect of transdermal corticosterone application on plasma corticosterone levels in pregnant Lacerta vivipara.

Relationships between hormones and behaviour can be explored by altering endogenous hormone levels, often through implantation of silastic tubing or osmotic pumps filled with a hormone or its agonists or antagonists. However, organisms in sensitive life-history stages (such as pregnancy) may be adversely affected by the surgical procedures associated with these manipulations, necessitating use of non-invasive techniques. We demonstrate that the application of a sesame oil-corticosterone mixture to the skin of pregnant female common lizards (Lacerta vivipara) elevates plasma levels of the hormone. Pregnant female L. vivipara were captured and treated daily for 1-20 days with the sesame oil-corticosterone mixture (experimental group) or with vehicle only (control group). Blood samples were collected and analyzed for corticosterone by radioimmunoassay. Baseline plasma corticosterone levels were elevated within 1 h in the experimental group. Similar levels ( approximately 145 ng/ml) were found over the subsequent 2 days, and by day 5 had risen significantly higher ( approximately 281.9 ng/ml), where they remained for the duration of the experiment. These increases are comparable to those found in other species using related techniques. No significant changes in plasma corticosterone levels occurred in the control group. Finally, corticosterone levels also were determined for untreated females that were captured, held overnight, sampled, and released to access to the natural range of basal corticosterone levels. Basal plasma levels of corticosterone in pregnant females varied among individuals independently of female body size or corpulence.