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• XRDCT is used to characterise unique multiphase cultural heritage geomaterials (CHG). • 3D mapping of crystalline phases is carried out non-destructively or non-invasively. • Qualitative/quantitative phase analysis and 3D imaging are simultaneously performed. • Potential and limits of XRDCT for new CHG applications are critically discussed. • New analytical perspectives in the characterisation of heterogeneous CHG are proposed. The present work describes the high potential of the recently developed synchrotron X-ray diffraction computed tomography (XRDCT) for 3D mapping of crystalline and amorphous phases in Geomaterials of Cultural Heritage (CHG). The paper critically discusses the promising results and limitations of XRDCT in Cultural Heritage applications. XRDCT has been applied herein to diverse CHG materials, spanning from archaeological ceramics, and stone conservation treatments to meteorites, at a microscale. Although these materials are very complex systems from a chemical, mineralogical and microstructural point of view, this innovative technique proves effective capability to access the real spatial distribution and semi-quantification of crystallographic phases within materials in a totally non-destructive and/or non-invasive way. [ABSTRACT FROM AUTHOR]

Clinical outcomes of advanced melanoma of unknown primary (MUP) in the era of novel therapies have been scarcely studied. To investigate the efficacy and safety of systemic treatments in patients with advanced MUP compared to patients with stage-matched melanoma of known cutaneous primary (cMKP). Based on the nationwide MelBase prospective database, this study included advanced melanoma patients treated from March 2013 to June 2021 with first-line immunotherapies, targeted therapies, or chemotherapy. Co-primary outcomes were progression-free survival and overall survival. Secondary outcome was treatment-related toxicities. Multivariate and propensity score analyses were performed. Of 1882 patients, 265 (14.1%) had advanced MUP. Patients with advanced MUP displayed more often unfavorable initial prognostic factors than those with cMKP. Progression-free and overall survival did not differ significantly between the groups (P =.73 and P =.93, respectively), as well as treatment-related toxicity rate and severity, regardless of treatment type. No record of standard diagnostic criteria of MUP used in the participating centers. Although patients with MUP had less favorable baseline prognostic factors, they benefited from the novel therapies as much as those with cMKP. They should be managed according to similar strategies. [ABSTRACT FROM AUTHOR]

Background: Late-onset adverse events (AEs) of anti-programmed cell death 1 (anti-PD1) antibodies have not been systematically described.Objectives: The purpose was to evaluate late-onset AEs in melanoma patients treated with anti-PD1 administered for at least 2 years in a real-life setting.Methods: Patients were screened from MelBase, a French multicentric biobank dedicated to the prospective follow up of unresectable stage III or IV melanoma. The study included 119 patients who received anti-PD1 during at least 2 years from January 2013 to November 2019. Median follow up was 41.7 months (range, 25.2-57.5 months). Fifty-three patients received nivolumab and 66 patients received pembrolizumab.Results: AEs occurred in 99 patients (83%) with a median time of 13.3 months (range, 0-53.9 months), including severe AEs (grade 3 or 4) in 30 patients (30%). Late-onset AEs, mostly grades 1 or 2, occurred in 51 (43%) patients and led to 5 (4%) hospitalizations, of which 4 were severe. Factors associated with late-onset AEs in multivariate analysis were early-onset AEs (within the first 2 years of treatment) and treatment duration (P = .02 and P = .03, respectively).Conclusions: Our data demonstrate the possibility of late-onset AEs occurring after 2 years of anti-PD1 therapy. Late-onset AEs appear frequently and were mostly mild or moderate. Early-onset AEs and prolonged anti-PD1 treatment may increase the risk of late-onset AEs. [ABSTRACT FROM AUTHOR]

• The use of DAP for consolidation of lime-based mortar was investigated. • The effects induced by different DAP concentrations were highlighted. • Additional post-treatment limewater application was used on some specimens. • Colour changes as a result of different DAP treatments are discussed. • DAP treatment noticeably improved the mechanical and cohesion properties. The paper investigates the use of di-ammonium hydrogen phosphate (DAP) as a possible consolidation treatment for lime-based mortars. Different DAP concentrations are proposed, additional post-treatment limewater application is used on some specimens. The results of application were evaluated in terms of mechanical property modification (dynamic elastic modulus, weight loss due to the peeling test), penetration depth, consolidant's distribution, colour change and water transport properties. Newly-precipitated phosphate-based phases were detected after the treatment and the relation towards treatment modality (i.e. DAP solution molarity and further limewater application) was evaluated. In the case of mechanical improvement, the outcomes indicate that a phosphate-based treatment is highly promising for mortar consolidation. Some non-negligible colour change was detected as a result of DAP application. [ABSTRACT FROM AUTHOR]

Inorganic-mineral treatments are commonly applied to decayed stone substrates in order to slow down the decay processes, through the partial transformation of the original stone material into newly-formed crystalline phases. The purpose of this study is to explore the effects induced by a promising consolidating treatment based on diammonium hydrogenphosphate (DAP) solutions on Noto limestone, a porous carbonatic matrix used as ornamental stone in the south of Italy. The research findings, obtained combining water absorption by capillarity measurements, mercury intrusion porosimetry (MIP) and synchrotron radiation X-ray micro-computed tomography (SR-μCT), demonstrate that the DAP consolidation induces microstructural modifications of the stone in terms of porosity and pore size distribution, changing the capillarity absorption values and decreasing the sorptivity speed. This study paves the way to a deeper investigation of the effects induced by a wider range of conservation treatments to the 3D microstructural features of porous geomaterials, by using an innovative multi-scale approach. • DAP solutions react with carbonatic stones and form phosphate phases on pore walls. • The crystallization of new phases modifies the water absorption by capillarity. • DAP treatments reduce the total open porosity and modify the pore size distribution. • MIP and SR-μCT are compared to study the 3D pore network of porous stone materials. • 3D microstructural features of treated stone are explored by a new multiscale approach. [ABSTRACT FROM AUTHOR]

Abstract Triclosan (TCS) is an antimicrobial agent used in diverse personal care products that is considered as an emerging contaminant of both aquatic and terrestrial ecosystems. Although TCS aquatic ecotoxicity is well known, information on the presence and effects on terrestrial organisms is still scarce. This study was aimed at exploring the embryotoxicity of TCS to the yellow-legged gull (Larus michahellis) induced by the in-ovo injection of 150 ng TCS/g egg weight. Effects of TCS on embryo morphological traits (i.e. body mass, tarsus length and head size). Moreover, oxidative and genetic effects were assessed in the embryo liver, by measuring the amount of reactive oxygen species (ROS), the activity of antioxidant (superoxide dismutase and catalase) and detoxifying (glutathione S -transferase - GST) enzymes, the levels of lipid peroxidation and DNA fragmentation. After the injection, the concentration of TCS measured in the yolk of unincubated eggs (159 ± 35 ng/g wet weight, ww) was close to the expected concentration. Triclosan was found in residual yolk (2.9 ± 1.1 ng/g ww), liver (2.3 ± 1.1 ng/g ww) and brain (0.2 ± 0.1 ng/g ww) of embryos soon before hatching. Triclosan did not significantly affect embryo morphological traits, while it increased ROS levels and promoted GST activity, inducing the onset of both oxidative and genetic damage. This study demonstrated, for the first time in a wild euriecious bird species with mixed habits, that TCS can be maternally transferred to developing embryos, representing a potential threat for offspring. Graphical abstract Image 1 Highlights • Embryotoxicity of Triclosan on the yellow-legged gull was investigated. • Triclosan levels in yolk of gull eggs was experimentally modulated. • Triclosan did not alter development of gull embryos. • Triclosan induced an oxidative stress situation in the liver of embryos. Triclosan induced oxidative stress in yellow-legged gull embryos. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Diammonium hydrogenphosphate (DAP) solutions consolidate decayed carbonatic stones. • The formed phases depend on treatment method, DAP molarity and stone microstructure. • Cutting-edge techniques are discussed to identify similar crystalline phases. • The formation of hydroxyapatite is unambiguously demonstrated. • Variables which might affect the treatment effectiveness are discussed. Abstract Diammonium hydrogenphosphate (DAP) is a water soluble consolidant for decayed carbonatic materials of historical buildings. The reaction of DAP solutions with polycrystalline calcite of marbles is non-stoichiometric and forms a calcium phosphates mixture whose identification is tricky and controversial. This study investigated how the DAP molarity, the treatment method and the microstructure of the stone influence the formation of specific phases. Thermal treatments and cutting-edge techniques (XRD with synchrotron radiation in transmitting geometry and high resolution FTIR microspectroscopy) were used to overcome the analytical limits of the more conventional methods, shading light to an in depth evaluation of DAP consolidating processes and treatment conditions. [ABSTRACT FROM AUTHOR]

Half of the cancer patients are treated with radiotherapy to obtain tumor control while minimizing radiation toxicity. In this context, hypoxia is known to determine treatment resistance, driving tumor relapse after treatment. Therefore, we investigated the role of microvasculature density and morphology in shaping the tissue oxygen distribution and consequently affecting the treatment outcome. We developed an advanced computational model to describe oxygen delivery in the vascular network and the surrounding tissue. A peculiar aspect of the model is its mesoscale mixed-dimensional approach, which allows the explicit inclusion of vascular network geometry and the description of the red blood cells' effect. The oxygen delivery is modeled considering both diffusive and convective phenomena. A 30 × 2Gy RBE treatment is delivered in silico simulating photons, protons, and carbon ions. First, we estimated the surviving fraction by the classical linear quadratic model modified to account for the oxygen effect. Then, leveraging the 3D description of the surviving fraction at the microenvironment scale, we compute the local tumor control probability (LTCP) in different oxygenation states (reference, acute hypoxia, high oxygen consumption). We report correlations between the LTCP and the hypoxic volume fractions (with pO 2 lower than 1 mmHg) starting with photons. These hypoxic regions are present locally, even in highly vascularized tissue, if the network is not uniformly distributed, as it might be in cancer. They are also present in tissue with low microvascular density, even with regular morphology. Interestingly, the domain considered is comparable to or smaller than the clinical imaging standard voxel dimension, and the average oxygen partial pressure in the tissue region fails to spot treatments with low LTCP, questioning whether these hypoxia areas are visible clinically via imaging. Protons have a similar effect, highlighting a similar behavior across the oxygenation levels at the microscale level. Finally, carbon ions seem more effective than photons and protons in the presence of hypoxia due to the lower oxygen effect at high LET. For this reason, the treatment with carbon ions results in high LTCPs, whatever vascular network is considered (density and morphology differences). These results show the effect of microvascular density and regularity on the radiotherapy outcome and they help us understand how the microvascular network morphology affects tumor oxygenation and the radiotherapy outcome. [ABSTRACT FROM AUTHOR]

• Solutions based on the action of diammonium hydrogen phospha are used as consolidants for carbonate stones. • 4D SR-μCT is employed to monitor the effects induced during the consolidating treatment on the same sample. • The reaction process is shown as time-dependent, with significant changes occurring within the first hour of treatment. • Changes in the stone's porous microstructure are shown and demonstrated. • The effect of solution molarity on the consolidating process is asserted. Diammonium hydrogen phosphate (DAP) solutions are used as consolidants for carbonate stone materials through the crystallization whithin the original matrix of newly formed crystalline phases. However, the formation mechanism of the new phases within the stone microstructure, and their effects on the porous system, strongly depend on the DAP molarity, the treatment method, and the stone microstructure. In this study, we obtained real-time quantitative information on the structural evolutions induced by the treatment process on the Noto limestone, a porous carbonate stone used as a building stone since antiquity, by synchrotron X-ray Microtomography. With the aid of 4D image analysis, microstructural modifications in terms of porosity, interconnection, and pore size distribution have been demonstrated in different stadia of the consolidation process, and the influence of molarity was asserted. This study paves the way for a deeper understanding of consolidation mechanisms and the effects induced overtime on the 3D microstructural features of porous materials by inorganic treatment. [ABSTRACT FROM AUTHOR]

The consequences of exposure to particulate matter (PM) have been thoroughly investigated in humans and other model species, but there is a dearth of studies of the effects of PM on physiology and life-history traits of non-human organisms living in natural or semi-natural environments. Besides toxicological relevance, PM has been recently suggested to exert epigenetic effects by altering DNA methylation patterns. Here, we investigated for the first time the association between the exposure to free-air PM 10 and DNA methylation at two loci (‘poly-Q exon’ and ‘5′-UTR’) of the Clock gene in blood cells of the nestlings of a synanthropic passerine bird, the barn swallow ( Hirundo rustica ). The Clock gene is a phylogenetically highly conserved gene playing a major role in governing circadian rhythms and circannual life cycles of animals, implying that change in its level of methylation can impact on important fitness traits. We found that methylation at both loci significantly increased with PM 10 levels recorded few days before blood sampling, and also with PM 10 exposure experienced by the mother during or shortly before egg laying. This study is the first where methylation at a functionally important gene has been shown to vary according to the concentration of anthropogenic pollutants in any animal species in the wild. Since early-life environmental conditions produce epigenetic effects that can transgenerationally be transmitted, DNA methylation of genes controlling photoperiodic response can have far reaching consequences for the ecology and the evolution of wild animal populations. [ABSTRACT FROM AUTHOR]

Abstract: Atrophic body gastritis is considered an outcome of H. pylori infection at high risk for gastric cancer. Immunoproteomics has been used to detect H. pylori antigens, which may act as potential markers for neoplastic disease and may be used in specific serological tests. We used immunoproteome technology to identify H. pylori antigens, recognized by sera from patients with atrophic body gastritis. Here, we performed 2DE protein maps of H. pylori strain 10K, probed against single sera from 3 groups of H. pylori-positive patients (atrophic body gastritis; intestinal-type gastric cancer; peptic ulcer) and negative controls. Immunoreactive spots were identified by MALDI-TOF–MS. A total of 155 immunoreactive spots were detected corresponding to 14.1% of total spots detected in our reference map of H. pylori strain 10K. Sera from atrophic body gastritis (40.5±2%) and gastric cancer patients (25.9±1.8%) showed a significantly higher and stronger mean immunoreactivity versus H. pylori antigens compared to peptic ulcer patients (11.2±1.3%). The average intensity of immunoreactivity of sera from atrophic body gastritis and gastric cancer patients was significantly stronger compared to peptic ulcer patients. Sera from atrophic body gastritis and gastric cancer patients differentially recognized 17 H. pylori spots. Immunoproteome technology may discriminate between different H. pylori-related disease phenotypes showing a serological immunorecognition pattern common to patients with gastric cancer and atrophic body gastritis, its precursor condition. This tool may be promising for developing specific serological tests to identify patients with gastritis at high risk for gastric cancer, to be evaluated in prospective investigations. [ABSTRACT FROM AUTHOR]

Abstract: Among apicomplexan parasites, the coccidia and Cryptosporidium spp. are important pathogens of livestock and humans, and the environmentally resistant stage (oocyst) is essential for their transmission. Little is known of the chemical and molecular composition of the oocyst wall. Currently, the only parasite molecules shown to be involved in oocyst wall formation are the tyrosine-rich proteins gam56, gam82 and gam230 of Eimeria spp. and the cysteine-rich proteins COWP1 and COWP8 of Cryptosporidium parvum. In the present study, we searched the ToxoDB database for the presence of putative Toxoplasma gondii oocyst wall proteins (OWPs) and identified seven candidates, herein named TgOWP1 through TgOWP7, showing homology to the Cryptosporidium COWPs. We analysed a cDNA library from partially sporulated oocysts of T. gondii and cloned the full-length cDNAs encoding TgOWP1, TgOWP2 and TgOWP3, which consist of 499, 462 and 640 amino acids, respectively. The three proteins share 24% sequence identity with each other and a markedly similar overall structure, based on the presence of an N-terminal leader peptide followed by tandem duplications of a six-cysteine amino acid motif closely related to the Type I repeat of COWPs. Using antisera to recombinant TgOWP1, TgOWP2 and TgOWP3, we showed by Western blot that these molecules are expressed in T. gondii oocysts but are not detectable in tachyzoites. The solubilisation of TgOWP1–3 strictly depended on the presence of reducing agents, consistent with a likely involvement of these proteins in multimeric complexes mediated by disulphide bridges. Immunofluorescence analysis allowed the localisation of TgOWP1, TgOWP2 and TgOWP3 to the oocyst wall. Additionally, using immunoelectron microscopy and the 1G12 monoclonal antibody, TgOWP3 was specifically detected in the outer layer of the oocyst wall, thus representing the first validated molecular marker of this structure in T. gondii. [ABSTRACT FROM AUTHOR]

Abstract: Bioinformatic data show that, in addition to TRAP-C1, Cryptosporidium parvum encodes 11 thrombospondin-related proteins (CpTSP2 through CpTSP12), none of which has been characterized yet. We describe herein the cloning of a 2048bp-long sporozoite cDNA encoding CpTSP8, a type I integral membrane protein of 614 amino acids, possessing three thrombospondin type I (TSP1) repeats and one epidermal growth factor (EGF)-like domain. Transcriptionally, CpTSP8 is represented by a fully spliced and two immature mRNA forms, in which the intron is either totally or partially retained. Immunofluorescence analysis detected CpTSP8 in the apical complex of both sporozoites and type I merozoites, and showed that, upon sporozoite exposure to host cells in vitro, the protein is translocated onto the parasite surface as typical of micronemal proteins (MICs). Accordingly, double immunofluorescence localized CpTSP8 to C. parvum micronemes, prompting us to rename it CpMIC1 in agreement with the current MICs nomenclature. [Copyright &y& Elsevier]

Abstract: Objective: Biallelic ablation of VGF determines a dwarf phenotype. VGF precursor protein encodes for different biologically active peptides none of which has been related to growth or muscular abnormalities. Here we present the first attempt to fill this gap. We tested the hypothesis that a recently identified VGF-derived peptide, TLQP-21, shown to centrally modulate metabolic functions, could also modulate growth hormone (GH)-axis and muscle strength. Design: Adult male mice were chronically icv injected with TLQP-21 (15μg/day for 14 days). Physiological, molecular and behavioral parameters related to the GH/IGF-1-axis were investigated. Results: Except for a reduction in the soleus weight, TLQP-21 did not affect GH/IGF-1-axis mediators, muscle strength and muscle weight. Conclusions: Results collected exclude a role for TLQP-21 in modulating the GH/IGF1-axis and muscle functions. VGF-derived peptides involved in the dwarf phenotype of VGF−/− mice have to be identified yet. [Copyright &y& Elsevier]

We have recently characterised, in the virulent strain RH of Toxoplasma gondii, three glycosylphosphatidylinositol-anchored surface antigens related to SAG1 (p30) and encoded by highly homologous, tandemly arrayed genes named SAG5A, SAG5B and SAG5C. In the present study, we compared the genomic organisation of the SAG5 locus in strains belonging to the three major genotypes of T. gondii. Southern blot analysis using a SAG5-specific probe produced two related but distinct hybridisation patterns, one exclusive of genotype I virulent strains, the other shared by avirulent strains of either genotype II or genotype III. To understand the molecular bases of this intergenotypic heterogeneity, we cloned and sequenced the SAG5 locus in the genotype II strain Me49. We found that in this isolate the SAG5B gene is missing, with SAG5A and SAG5C laying contiguously. This genomic arrangement explains the hybridisation profiles observed for all the avirulent strains examined and indicates that the presence of SAG5B is a distinctive trait of genotype I. Furthermore, we identified two novel SAG1-related genes, SAG5D and SAG5E, mapping respectively 1.8 and 4.0 kb upstream of SAG5A. SAG5D is transcribed in tachyzoites and encodes a polypeptide of 362 amino acids sharing 50% identity with SAG5A-C, whereas SAG5E is a transcribed pseudogene. We also evaluated polymorphisms at the SAG5 locus by comparing the coding regions of SAG5A-E from strains representative of the three archetypal genotypes. In agreement with the strict allelic dimorphism of T. gondii, we identified two alleles for SAG5D, whereas SAG5A, SAG5C and SAG5E were found to be three distinct nucleotide variants. The higher intergenotypic polymorphism of SAG5A, SAG5C and SAG5E suggests that these genes underwent a more rapid genetic drift than the other members of the SAG1 family. Finally, we developed a new PCR–restriction fragment length polymorphism method based on the SAG5C gene that is able to discriminate between strains of genotype I, II and III by a single endonuclease digestion. [Copyright &y& Elsevier]

Objective: To analyze the results of an enhanced laboratory-surveillance protocol for bloody diarrhea aimed at identifying children with Shiga toxin-producing Escherichia coli (STEC) infection early in the course of the disease toward the early identification and management of patients with hemolytic uremic syndrome (HUS).Study Design: The study (2010-2019) involved a referral population of 2.3 million children. Stool samples of patients with bloody diarrhea were screened for Shiga toxin (Stx) genes. Positive patients were rehydrated and monitored for hemoglobinuria until diarrhea resolved or STEC-HUS was diagnosed.Results: A total of 4767 children were screened; 214 (4.5%) were positive for either Stx1 (29.0%) or Stx2 (45.3%) or both Stx1+2 (25.7%); 34 patients (15.9%) developed STEC-HUS (0.71% of bloody diarrheas). Hemoglobinuria was present in all patients with HUS. Patients with Stx2 alone showed a greater risk of STEC-HUS (23.7% vs 12.7%) and none of the patients with Stx1 alone developed HUS. During the same period of time, 95 other patients were diagnosed STEC-HUS but were not captured by the screening program (26 had nonbloody diarrhea, 11 came from areas not covered by the screening program, and 58 had not been referred to the screening program, although they did meet the inclusion criteria). At HUS presentation, serum creatinine of patients identified by screening was significantly lower compared with that of the remaining patients (median 0.9 vs 1.51 mg/dL).Conclusions: Nearly 1% of children with bloody diarrhea developed STEC-HUS, and its diagnosis was anticipated by the screening program for Stx. The screening of bloody diarrhea for Stx is recommended, and monitoring patients carrying Stx2 with urine dipstick for hemoglobinuria is suggested to identify the renal complication as early as possible. [ABSTRACT FROM AUTHOR]

This work developed two smart greenhouses for the protected cultivation of banana and orchid seedlings. The greenhouses feature control and automation systems, bioclimatic architecture and strategies, and energy systems. A sensor network monitors indoor environmental variables, and a weather station monitors outdoor environmental variables. A computational system based on artificial intelligence is responsible for the autonomous control of the greenhouses. This article presents the development of an artificial lighting system for light supplementation in smart greenhouses. The artificial lighting system was defined from modeling and simulation in a computational tool. The proposed system was installed in two smart greenhouses in southern Brazil. The article also presents the development of methods for estimating electricity consumption based on assumptions and operational profiles of the system and the experimental measurement of the artificial lighting system performed according to the procedure described in technical standards. The article presents the energy performance of the agrivoltaic system applied to smart greenhouses. From August 2022 to July 2023, the final yield of the agrivoltaic systems of the smart greenhouses was 1418.91 kW h/kW P and 1490.68 kW h/kW P. The annual electricity consumption of the artificial lighting systems of the smart greenhouses ranges between 3290 kW h and 3825 kW h. [ABSTRACT FROM AUTHOR]

Les inhibiteurs de point de contrôle immunitaire (ICI), anti-CTLA-4 et anti-PD-1, ont révolutionné la prise en charge de certains cancers. Les myosites survenant sous ICI (ICI-Myo) sont des effets secondaires rares mais potentiellement graves. Leur description est récente et leur prise en charge n'est pas codifiée. L'objectif de cette étude rétrospective est de préciser les caractéristiques cliniques et paracliniques des ICI-Myo et d'évaluer les différentes stratégies thérapeutiques employées. Cette étude multicentrique rétrospective a inclus des patients ayant développé une Myosite suite à l'introduction d'un traitement par anti-PD-1 (n = 17), l'association anti-PD-1 + Anti-CTLA-4 (n = 2), ou anti-PD-L1 (n = 1) pour mélanome (n = 16) ou tumeur broncho-pulmonaire (n = 4). Les données cliniques, paracliniques et thérapeutiques de patients suivis entre 2016 et janvier 2020 ont été recueillies et analysées. Tous les patients présentaient un élément déficitaire et une augmentation des CPK et 17/20 au moins une anomalie musculaire morphologique (n = 10), electromyographique (n = 11) et/ou histologique (n = 11). Les patients présentant une myocardite concomittante, dont l'issue malgré les traitements reste la plupart du temps fatale, ont été exclus (n = 4). Les patients étaient classés ICI-Myo s'ils présentaient une forme typique (cf Touat M et al. Neurology 2018). Dans le cas contraire, ils étaient considérés comme ICI-Myo-atypique. Les patients présentant une ICI-Myo étaient sévères s'ils présentaient un déficit musculaire ≤ 3 (Échelle MRC) sur au moins un faisceau musculaire, des troubles de déglutition ou une atteinte des muscles respiratoires. Dans le cas contraire, ils constituaient le groupe ICI-Myo-modérée. Parmi les 20 patients inclus (16 hommes, 4 femmes, d'âge médian 70 ans, 45-87) quatre présentaient une ICI-Myo atypique. Selon les critères de classification en vigueur, ils présentaient une dermatomyosite (n = 2, dont une avec anticorps anti-TIF1-g), une myosite de chevauchement de survenue tardive et une myopathie nécrosante auto-immune (anticorps anti-HMGCR négative). Une rémission complète n'était jamais obtenue malgré l'association Corticoides, IV-Ig et Immunosuppresseur pour ¾ des patients. Parmi les 16 patients avec ICI-Myo typique, survenant après un délai habituel de 2 cures (1-9), neuf avaient une atteinte modérée et six une atteinte sévère. Seul un patient présentait des auto-anticorps (anti-récepteur de l'acétylcholine, antérieurs au traitement, sans avoir développé de myasthénie). Le taux médian de CPK (3-55 N) ne différait pas entre les deux groupes (5 vs 18 N, p = 0,19). En plus de l'arrêt de l'ICI, le traitement des patients ICI-Myo modérée était réparti comme suit : absence (n = 1), Prednisone ≤ 0,5 mg/kg/J (n = 5), Prednisone 1 mg/kg/J (n = 4). Tous les patients étaient en rémission complète de l'ICI-Myo, permettant une diminution puis arrêt du traitement en 10 semaines (4-30). Le traitement des patients ICI-Myo sévère était Prednisone 1 mg/kg/J (n = 1), Methylprednisolone-Prednisone (n = 4), Methylprednisolone-Prednisone + IV-Ig (n = 1). Tous les patients répondaient favorablement et le traitement était interrompu en 11 semaines (10-59). Le spectre clinique des myosites survenant sous ICI est probablement plus large que décrit antérieurement. Il apparaît légitime de pousser les investigations diagnostiques afin de dépister des formes atypiques, potentiellement associées au cancer et répondant mal aux traitements immunomodulateurs. Les formes typiques semblent répondre favorablement aux corticoïdes seuls, dont la dose et la durée doivent être adaptées à la sévérité clinique, afin de préserver au mieux l'immunité anti-tumorale. [ABSTRACT FROM AUTHOR]

• The behaviour of DAP consolidation on artificially weathered mortars was investigated. • Multi-analytical approach examining physical properties was used. • Novel protocol for the evaluation of surface condition was proposed. • DAP treatment effectively restored the weathered mortars. The present paper investigates the effectiveness of di-ammonium hydrogen phosphate (DAP) as a consolidation treatment for artificially weathered lime-based mortars. Laboratory prepared samples were exposed to repeated freeze-thaw cycles and then subjected to 2.0 M DAP solution via 24 h poultice. The microstructural variations due to freeze-thaw cycles and the effects induced by the subsequent DAP consolidation were assessed with the use of a multi-analytical approach combining optical observations, weight variations, dynamic elastic modulus change and peeling test outcomes. The results indicate that DAP treatment significantly restored the weathered mortars in terms of physical and cohesive properties. The correlation between the weight loss and surface degradation by the peeling test examination was projected. The new properties of weathered and consolidated mortars are critically discussed with an eye on their expected behaviour in the field of Built Heritage conservation. Lastly, as a chief outcome of this study, a novel protocol for the evaluation of surface cohesion through peeling tests combined with image analysis is proposed. [ABSTRACT FROM AUTHOR]

• During host cell travrsal Toxoplasma gondii sporozoites reside in the parasitophorous vacuole. • Traversing sporozoites posteriorly release GRA-positive membranous tails named SSTs. • We provide the first known ultrastructural evidence of sporozoite cell escape and cell-to-cell passage. Toxoplasma gondii has a worldwide distribution and infects virtually all warm-blooded animals, including humans. Ingestion of the environmentally resistant oocyst stage, excreted only in the feces of cats, is central to transmission of this apicomplexan parasite. There is vast literature on the host and T. gondii tachyzoite (proliferative stage of the parasite) but little is known of the host-parasite interaction and conversion of the free-living stage (sporozoite inside the oocyst) to the parasitic stage. Here, we present events that follow invasion of host cells with T. gondii sporozoites by using immunofluorescence (IF) and transmission electron microscopy (TEM). Several human type cell cultures were infected with T. gondii sporozoites of the two genotypes (Type II, ME49 and Type III, VEG) most prevalent worldwide. For the first known time, using anti-rhoptry neck protein 4 (RON4) antibodies, the moving junction was visualized in sporozoites during the invasion process and shortly after its completion. Surprisingly, IF and TEM evaluation revealed that intracellular sporozoites release, at their posterior end, long membranous tails, herein named sporozoite-specific trails (SSTs). Differential permeabilization and IF experiments showed that the SSTs are associated with several dense granule proteins (GRAs) and that their membranous component is of parasite origin. Furthermore, TEM observations demonstrated that SST-associated sporozoites are delimited by a typical parasitophorous vacuole, which is retained during parasite exit from the host cell and during cell-to-cell passage. Our data strongly suggest that host cell traversal by T. gondii sporozoites relies on a novel force-producing mechanism, based on the massive extrusion at the parasite posterior pole of GRA-associated membranous material derived from the same pool of membranes forming the intravacuolar network. [ABSTRACT FROM AUTHOR]