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Este artículo expone las territorialidades conflictivas que se generan en el basural a cielo abierto del Partido de Luján y la forma en que estas tensiones condicionan la gestión integral de residuos sólidos urbanos [RSU], la resiliencia y la sostenibilidad local. Para ello, se propone examinar el negocio de los materiales reciclables y las luchas de poder entre los distintos actores sociales que conviven en el predio municipal.A partir de la observación directa y la revisión de documentos se busca evidenciar las particularidades que convierten al basural en un territorio en riesgo y en disputa. Mediante las entrevistas en profundidad a actores clave se busca conocer y comprender las dinámicas territorializadoras que se originan a partir de las formas en que se ejerce, se resiste y se disputa el manejo de la basura. A partir de lo estudiado, se evidencia que la población que se dedica a la recuperación de materiales reciclables vive en situación de injusticia social, vulnerabilidad ambiental e informalidad laboral. Esta situación de emergencia crónica demanda prioridad en la agenda pública desde una perspectiva que refuerce el componente social de la sostenibilidad. Los resultados demuestran que es prioritario resolver los conflictos preexistentes en el territorio vinculados a informalidad de la comercialización de los RSU para implementar una gestión integral inclusiva y asociada para el desarrollo sostenible local.

The documentary “Guerra do Paraguai: a nossa grande guerra” (RUAS, 2015) covers the history of the Paraguayan War, blending testimonies of intellectuals and public figures with the narrative of the facts, illustrated by the dramatization/reconstruction of the narrated scenes. In analyzing t his production, this paper aims at reflecting on the ways in which the cultural industry disseminates productions that appropriate historical issues and constitute notions and meanings that are socially shared. The central concept is the multiperspectivity expressed in the documentary and the identified problem is related to the fact that this is inclined to a simplistic relativism and creates a negative view of the Paraguayan nation in such historical process, also explaining ideological inclinations in the historiographic debate.

This article belongs to the Special Issue Optical Nanoparticles for Biomedicine The vertiginous increase in the use of extracellular vesicles and especially exosomes for therapeutic applications highlights the necessity of advanced techniques for gaining a deeper knowledge of their pharmacological properties. Herein, we report a novel chemical approach for the robust attachment of commercial fluorescent dyes to the exosome surface with covalent binding. The applicability of the methodology was tested on milk and cancer cell-derived exosomes (from U87 and B16F10 cancer cells). We demonstrated that fluorescent labeling did not modify the original physicochemical properties of exosomes. We tested this nanoprobe in cell cultures and healthy mice to validate its use for in vitro and in vivo applications. We confirmed that these fluorescently labeled exosomes could be successfully visualized with optical imaging. This study was supported by the Comunidad de Madrid, projects: “Y2018/NMT-4949 (NanoLiver-CM)” and “S2017/BMD-3867 (RENIM-CM)”; it was also co-funded by the European Structural and Investment Fund. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and it is a Severo Ochoa Center of Excellence (SEV-2015-0505). JV was supported by grants from Instituto de Salud Carlos III (PI18/01833), co-funded by European Regional Development Fund (ERDF) and from Comunidad de Madrid, project “S2017/BMD2737 (ExoHep-CM)”, co-funded by European Structural and Investment Fund. A. Santos-Coquillat is grateful for the financial support from Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III Sara Borrell Fellowship grant CD19/00136.

Stem-cell-derived extracellular vesicles (EVs) have demonstrated multiple beneficial effects in preclinical models of cardiac diseases. However, poor retention at the target site may limit their therapeutic efficacy. Cardiac extracellular matrix hydrogels (cECMH) seem promising as drug-delivery materials and could improve the retention of EVs, but may be limited by their long gelation time and soft mechanical properties. Our objective was to develop and characterize an optimized product combining cECMH, polyethylene glycol (PEG), and EVs (EVs–PEG–cECMH) in an attempt to overcome their individual limitations: long gelation time of the cECMH and poor retention of the EVs. The new combined product presented improved physicochemical properties (60% reduction in half gelation time, p &lt, 0.001, and threefold increase in storage modulus, p &lt, 0.01, vs. cECMH alone), while preserving injectability and biodegradability. It also maintained in vitro bioactivity of its individual components (55% reduction in cellular senescence vs. serum-free medium, p &lt, 0.001, similar to EVs and cECMH alone) and increased on-site retention in vivo (fourfold increase vs. EVs alone, p &lt, 0.05). In conclusion, the combination of EVs–PEG–cECMH is a potential multipronged product with improved gelation time and mechanical properties, increased on-site retention, and maintained bioactivity that, all together, may translate into boosted therapeutic efficacy.

The present study analyzes at the national level, the presence of circulating Legionella in the artificial aquatic systems of different facilities of all of them state-owned centers throughout Spain for 12 months. 1754 water samples from various state-owned centers were collected from January to December 2014. Samples were collected from the cooling towers and evaporative condensers (CTC), and water distribution networks such as domestic hot water (DHW), cold water for human consumption (CW), sprinkler irrigation systems (SIS), fire sprinkler systems (FSS), and water from decorative fountains (DF). All these facilities are considered, according to current regulations, as potential amplifying systems for bacteria and possible sources of infection by the generation of droplets and aerosols. The isolation and counting of Legionella in water samples was carried out using microbiological culture following the international normative UNE-EN-ISO 11,731:2007 (ISO 11,731:1998) and UNE-EN ISO 8199:2008 (ISO 8199:2005).The quantification of Legionella colonization, the annual distribution, and the geographical distribution of the Legionella isolates recovered in the water were analyzed. Besides, molecular techniques were used for the characterization of the Legionella non-pneumophila isolates. Legionella was recovered from 15.79% of the analyzed water samples. High colonization was more frequently detected in water samples from CTC, DHW, CW, and DF. Regarding the geographic distribution, positive samples of Legionella were obtained in 14 of the 18 Spanish locations analyzed. Legionella non-pneumophila was the most prevalent and was isolated from water samples from 13 different geographical locations (72%). Legionella anisa and Legionella jordanis were the most frequently non-pneumophila species isolated. Legionella donaldsonii was isolated for the first time in the water distribution networks in Spain. Legionella pneumophila sg 2-14 was detected in 13 locations and Legionella pneumophila sg 1 in 11 locations. Therefore, our study concludes that the presence of Legionella pneumophila and Legionella non-pneumophila species in these systems can be a potential threat to public health and should be examined thoroughly with complementary techniques, such as molecular techniques as a screen for routine diagnosis.

Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodality imaging including invasive coronary angiography, cardiac magnetic resonance (CMR), and hybrid 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). A total of 43 pigs were operated on and were followed for 120 ± 37 days with monthly multimodality imaging. 24 pigs (56%) died during the follow-up. Severe LAD luminal stenosis was documented in all survivors. In the group of 19 long-term survivors, 17 (90%) developed left ventricular systolic dysfunction [median LVEF of 35% (IQR 32.5-40.5%)]. In 17/17, at-risk territory was viable on CMR and 14 showed an increased glucose uptake in the at-risk myocardium on 18FDG-PET/CT. The present pig model resembles most of the human hibernated myocardium characteristics and associated heart failure (systolic dysfunction, viable myocardium, and metabolic switch to glucose). This human-like model might be used to test novel interventions for nonrevascularizable coronary artery disease and ischemia heart failure as a previous stage to clinical trials. his study has been partially funded by the Horizon 2020 European Research Area Network on Cardiovascular Diseases (ERA-CVD) Joint Transnational Call “AC16/00021: FAT-4HEART,” by the Spanish Society of Cardiology through a “Translational Research grant 2019,” and by the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF) through a FIS grant (Ref # PI16/02110). Imaging phenotyping was partially supported by the Comunidad de Madrid (S2017/BMD-3867 RENIM-CM) and cofunded with European structural and investment funds. The CNIC is supported by the ISCIII, the Ministerio de Ciencia e Innovación and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). Sí

We communicate the interference of a compound of the blood collection tube with the accuracy of a validated high-pressure liquid chromatography method with ultraviolet detection for quantifying voriconazole levels, which led to false positive results. This could have serious consequences for patient management. Our advice is to implement external assessment programs.

The DNA repair enzyme poly(ADP-ribose) polymerase 1 (PARP-1) is overexpressed in glioblastoma, with overall low expression in healthy brain tissue. Paired with the availability of specific small molecule inhibitors, PARP-1 is a near-ideal target to develop novel radiotherapeutics to induce DNA damage and apoptosis in cancer cells, while sparing healthy brain tissue. Methods: We synthesized an 131I-labeled PARP-1 therapeutic and investigated its pharmacology in vitro and in vivo. A subcutaneous tumor model was used to quantify retention times and therapeutic efficacy. A potential clinical scenario, intratumoral convection-enhanced delivery, was mimicked using an orthotopic glioblastoma model combined with an implanted osmotic pump system to study local administration of 131I-PARPi (PARPi is PARP inhibitor). Results: 131I-PARPi is a 1(2H)-phthalazinone, similar in structure to the Food and Drug Administration–approved PARP inhibitor AZD-2281. In vitro studies have shown that 131I-PARPi and AZD-2281 share similar pharmacologic profiles. 131I-PARPi delivered 134.1 cGy/MBq intratumoral injected activity. Doses to nontarget tissues, including liver and kidney, were significantly lower. Radiation damage and cell death in treated tumors were shown by p53 activation in U87-MG cells transfected with a p53-bioluminescent reporter. Treated mice showed significantly longer survival than mice receiving vehicle (29 vs. 22 d, P < 0.005) in a subcutaneous model. Convection-enhanced delivery demonstrated efficient retention of 131I-PARPi in orthotopic brain tumors, while quickly clearing from healthy brain tissue. Conclusion: Our results demonstrate 131I-PARPi’s high potential as a therapeutic and highlight PARP’s relevance as a target for radionuclide therapy. Radiation plays an integral role in brain tumor therapy, and radiolabeled PARP therapeutics could ultimately lead to improvements in the standard of care.

Exosomes are cell-derived nanovesicles with a proven intercellular signaling role in inflammation processes and immune response. Due to their natural origin and liposome-like structure, these nanometer-scale vesicles have emerged as novel platforms for therapy and diagnosis. In this work, goat milk exosomes are isolated and fully characterized in terms of their physicochemical properties, proteomics, and biochemical profile in healthy mice, and used to detect inflammatory processes by optical imaging. For the in vitro and in vivo experiments, the exosomes are covalently labeled with the commercial fluorophores sulfo-Cyanine 5 and BODIPY-FL to create nanoprobes. In vitro studies using confocal imaging, flow cytometry, and colorimetric assays confirm the internalization of the nanoprobes as well their lack of cytotoxicity in macrophage populations RAW 264.7. Optical imaging in the mouse peritoneal region confirms the in vivo ability of one of the nanoprobes to localize inflammatory processes. In vivo imaging shows exosome uptake in the inflamed peritoneal region, and flow-cytometric analysis of peritonitis exudates confirms the uptake by macrophage and neutrophil populations. These results support the promising use of goat milk exosomes as natural probes in the detection of inflammatory processes. This study has been funded by Instituto de Salud Carlos III, through the project "PI20/01632", co-funded by European Regional Development Fund (ERDF), "A way to make Europe" and by Comunidad de Madrid, project "Y2018/NMT-4949 (NanoLiver-CM)" and "S2017/BMD-3867 (RENIM-CM)", co-funded by European Structural and Investment Fund. This work has been also supported by "Diagnosis and treatment follow-up of severe Staphylococcal Infections with Anti-Staphylococcal antibodies and Immune-PET - Grant Fundación BBVA a Equipos de Investigación Científica 2018". A. Santos-Coquillat is grateful for financial support to Consejería de Educación e Investigación, co-financed by European Social Fund (ESF) grant PEJD-2018-POST/BMD-9592. A. Santos Coquillat is also funded by Instituto de Salud Carlos III, co-funded by European Social Fund "Investing in your future" (grant CD19/00136). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation. The CNIO Proteomics Unit is funded by the H2020 project EPIC-XS (ref. 823839). Biomedical Imaging has been conducted at the Advanced Imaging Unit of the CNIC (Centro Nacional de Investigaciones Cardiovasculares Carlos III), Madrid, Spain.

Background Extensive coronary artery disease without revascularization options results in ischemic hibernated myocardium and ultimately heart failure (HF). A metabolic reprogramming of the heart characterized by a shift from fatty acids (FFA) to glucose as the preferential metabolic substrate is frequent in HF and hibernated myocardium. Previous studies in mouse models of HF have shown that high fat diet (HFD) is able to reverse the metabolic reprogramming of the heart and improve cardiac function. Here we used a translational large animal model of ischemic HF evaluated by state-of-the-art imaging modalities Methods IHM was generated in Yucatan minipigs (N=50) by progressive stenosis of the proximal left anterior descending (LAD) after surgical insertion of a casein ameroid around the artery. Pigs underwent a serial multimodality imaging study including magnetic resonance imaging (MRI), multi-tracer PET/CT (18FDG & 14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid (18F-FTHA) 19F-palmitate in-house synthetized), and invasive coronary angiography (ICA). Once hibernated myocardium with metabolic switch was documented (complete occlusion of LAD, LVEF Results The first part of the study was dedicated to establish the model in 42 pigs. Pigs were followed-up for 170±24 days with monthly ICA, MRI and PET/CT. Severe LAD stenosis was documented in all pigs 3–4 weeks after surgery. Mortality during follow-up was 57% (n=24) (15 peri-procedure, 2 between day 1 and 7, seven between day 7 and 45). Among those surviving beyond the sixth week, 90% (16/18) developed hibernated myocardium (mean LVEF 36±10%, absence of transmural delayed enhancement, contractile reserve and metabolic switch on PET/CT). In the second part of the study, 5 long-term survivors were allocated to receive HFD (20% extra lard), while 3 pigs served as controls. Mean LVEF before HFD initiation was 35±8%, and 36±5% in controls. Three months HFD was associated with a LVEF improvement in all treated animals (mean LVEF at the end of follow-up was 45±9%). Control animals on regular diet did not show any change in LVEF (35±5% at the end of follow-up) Conclusions We present a large animal model of HF due hibernated myocardium by placing an ameroid around the LAD. Mortality of this model is high (approx. 55%) but long-term survivors resemble all features seen in patients: LAD progressive stenosis with final occlusion but viable myocardium, LVEF deterioration and metabolic switch Feeding pigs with HFD to force cardiac reutilization of FFA, results in a consistent and large LVEF improvement in all animals Cardiac metabolic switch might be implicated in the pathogenesis of systolic dysfunction in hibernated myocardium and is a potential target for nutritional approaches

Trehalose analogues bearing fluorescent and click chemistry tags have been developed as probes of bacterial trehalose metabolism, but these tools have limitations with respect to in vivo imaging applications. Here, we report the radiosynthesis of the F-18-modified trehalose analogue 2-deoxy-2-[F-18]fluoro-D-trehalose ([F-18]-2-FDTre), which in principle can be used in conjunction with positron emission tomography (PET) imaging to allow in vivo imaging of trehalose metabolism in various contexts. A chemoenzymatic method employing the thermophilic TreT enzyme from Thermoproteus tenax was used to rapidly (15-20 min), efficiently (70% radiochemical yield; >= 95% radiochemical purity), and reproducibly convert the commercially available radiotracer 2-deoxy-2-[F-18]fluoro-D-glucose ([F-18]-2-FDG) into the target radioprobe [F-18]-2-FDTre in a single step; both manual and automated syntheses were performed with similar results. Cellular uptake experiments showed that radiosynthetic [F-18]-2-FDTre was metabolized by Mycobacterium smegmatis but not by various mammalian cell lines, pointing to the potential future use of this radioprobe for selective PET imaging of infections caused by trehalose-metabolizing bacterial pathogens such as M. tuberculosis. This work was funded by a grant from the National Institutes of Health, United States (R15 AI117670) to B.M.S. and P.J.W., as well as a Henry Dreyfus Teacher-Scholar Award from The Camille & Henry Dreyfus Foundation to B.M.S. (TH-17-034). A.Y.-T.H was supported by the Mount Holyoke College Lynk program. Dr. Wenyan Xu is thanked for assistance with kinetic analysis. The research leading to these results received funding from the Innovative Medicines Initiative, European Union (www.imi.europa.eu) Joint Undertaking under grant agreement no. 115337, whose resources comprise funding from EU FP7/2007-2013 and EFPIA, European Union companies in-kind contribution. This work was partially supported by the Ministry of Economy and Competitiveness, Spain TEC2015-73064-EXP and TEC2016-78052-R, ISCIII-FIS grants PI16/02037, co-financed by ERDF, European Union (FEDER) Funds from the European Commission, European Union, "A way of making Europe".

In cases where catheter-related candidemia (CRC) must be managed without catheter withdrawal, antifungal lock therapy using highly active anti-biofilm (HAAB) agents is combined with systemic treatment. However, the activity of HAAB agents has never been studied in in vivo models using bioluminescence. We assessed the efficacy of micafungin using a bioluminescent Candida albicans SKCA23-ACTgLuc strain in an animal model of CRC. We divided 33 female Wistar rats into five groups: sham (A), infected nontreated (B), treated with lock therapy (0.16 mg/ml) (C), systemically treated only (1 mg/kg) (D), and systemically treated+lock (E). Catheters were colonized 24 h before insertion into the femoral vein (day 0). Treatment started on day 1 and lasted 7 days, followed by 7 days of surveillance. Bioluminescence assays were carried out on days 1, 3, 5, and 14, together with daily monitoring of clinical variables. Postmortem microbiological cultures from the catheter and several tissue samples were also obtained. Overall, 28 rats (84.8%) completed the study. Group B animals showed significant weight loss at days 2, 4, and 5 compared with groups C and D (P < .05). In group B, no animals survived after day 7, 75% had CRC, and bioluminescence remained constant 5 days after catheter implantation. Positive catheter culture rates in groups C, D, and E were, respectively, 83.3%, 62.5%, and 25.0% (P = .15). Micafungin proved to be a HAAB agent when administered both systemically and in lock therapy in an animal model of CRC, although the bioluminescence signal persists after treatment. This persistence should be further analyzed.

Anais do XVII Congresso Internacional das Jornadas de Educaão História - teoria, pesquisa e prática - I Encontro da AIPEDH - Associação Iber-Americana de Pesquisadores em Educação História, realizado pela Universidade Federal da Integração Latino-Americana, entre 02, 03 e 04 de agosto de 2017. El documental “Guerra do Paraguai – A nossa Grande Guerra” (RUAS, 2015) trae en su contenido declaraciones de especialistas, narraciones y produce escenas con el objetivo de reconstruir y explicar la Guerra de la Triple Alianza, es importante resaltar que este documentario se presenta bajo la idea de multiperspectividad (SOUZA 2015), pero con ciertos límites teniendo en cuenta que se trata de una versión brasilera. El objetivo principal del presente trabajo es analizar como profesores brasileros y paraguayos interpretan los debates y abordajes sobre la Guerra de la Triple Alianza en el dicho documental. Desde ahí estudiar las interpretaciones de estos sujetos acerca de este documentario, y el aprendizaje histórico (SCHMIDT, 2014) de los mismos. Considerando la conciencia histórica (RÜSEN 2001), las relaciones con la cultura y la formación de la identidad nacional que ellos pueden colocar o direccionar en sus visiones Investigación realizada en el ámbito del proyecto “Didatica da História, Cultura Histórica e Indústria Cultural: perspectivas desde e sobre a América Latina”, ejecutado en la UNILA, con apoyo de la “Fundação Araucária”.

The use of click chemistry reactions for the functionalization of nanoparticles is particularly useful to modify the surface in a well-defined manner and to enhance the targeting properties, thus facilitating clinical translation. Here it is demonstrated that olefin metathesis can be used for the chemoselective functionalization of iron oxide nanoparticles with three different examples. This approach enables, in one step, the synthesis and functionalization of different water-stable magnetite-based particles from oleic acid-coated counterparts. The surface of the nanoparticles was completely characterized showing how the metathesis approach introduces a large number of hydrophilic molecules on their coating layer. As an example of the possible applications of these new nanocomposites, a focus was taken on atherosclerosis plaques. It is also demonstrated how the in vitro properties of one of the probes, particularly its Ca(2+) -binding properties, mediate their final in vivo use; that is, the selective accumulation in atherosclerotic plaques. This opens promising new applications to detect possible microcalcifications associated with plaque vulnerability. The accumulation of the new imaging tracers is demonstrated by in vivo magnetic resonance imaging of carotids and aorta in the ApoE(-/-) mouse model and the results were confirmed by histology.

The production of magnetic nanoparticles of utmost quality for biomedical imaging requires several steps, from the synthesis of highly crystalline magnetic cores to the attachment of the different molecules on the surface. This last step probably plays the key role in the production of clinically useful nanomaterials. The attachment of the different biomolecules should be performed in a defined and controlled fashion, avoiding the random adsorption of the components that could lead to undesirable byproducts and ill-characterized surface composition. In this work, we review the process of creating new magnetic nanomaterials for imaging, particularly for the detection of atherosclerotic plaque, in vivo. Our focus will be in the different biofunctionalization techniques that we and several other groups have recently developed. Magnetic nanomaterial functionalization should be performed by chemoselective techniques. This approach will facilitate the application of these nanomaterials in the clinic, not as an exception, but as any other pharmacological compound. The authors thank the Spanish Ministry of Science (SAF2011-25445), the Comunidad de Madrid (S2010/BMD-2326, Inmunothercan-CM, NANOCOPD-CIBERES-CIBERBBN-SEPAR), and the EU 7th Framework Program (FP7-PEOPLE-ITN-264864 Pinet and FP7-PEOPLE-2013-ITN CardioNext). Sí

Heart failure is one of the major cardiovascular problems worldwide, with Dilated cardiomyopathy (DCM) of ischemic origin is the most frequent cause. Design of novel therapies rely on the development of relevant animal models close to human anatomy and physiology. Ischemic DCM was induced in

Layered double hydroxides (LDH) with intercalated diclofenac, chloramphenicol and ketoprofen have been supported and dispersed in semicrystalline polylactic acid (PLA). The solids have been characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA) and Fourier-Transform infrared spectroscopy (FT-IR). Drug release from the systems prepared was followed by UV–vis spectroscopy. Release is almost complete after 24 h for ketoprofen from the drug-LDH systems, but lower values were measured for the other drugs (60 and 80%, respectively, for diclofenac and chloramphenicol); however, when supported on PLA the release was much slower and could be related to the degradation of the polymer.

Legionnaires' disease is a severe form of pneumonia, with worldwide relevance, caused by Legionella spp. Approximately 90% of all cases of legionellosis are caused by Legionella pneumophila, but other species can also be responsible for this infection. These bacteria are transmitted by inhalation of aerosols or aspiration of contaminated water. In Spain, environmental studies have demonstrated the presence of Legionella non-pneumophila species in drinking water treatment plants and water distribution networks. Aware that this evidence indicates a risk factor and the lack of routine assays designed to detect simultaneously diverse Legionella species, we analyzed 210 urine samples from patients presenting clinical manifestations of pneumonia using a semi-nested PCR for partial amplification of the 16S rDNA gene of Legionella and a diagnostic method used in hospitals for Legionella antigen detection. In this study, we detected a total of 15 cases of legionellosis (7.1%) and the first case of Legionnaires' disease caused by L. anisa in Spain. While the conventional method used in hospitals could only detect four cases (1.9%) produced by L. pneumophila serogroup 1, using PCR, the following species were identified: Legionella spp. (10/15), L. pneumophila (4/15) and L. anisa (1/15). These results suggest the need to change hospital diagnostic strategies regarding the identification of Legionella species associated with this disease. Therefore, the detection of Legionella DNA by PCR in urine samples seems to be a suitable alternative method for a sensitive, accurate and rapid diagnosis of Legionella pneumonia, caused by L. pneumophila and also for L. non-pneumophila species.

The functionalization of iron oxide superparamagnetic nanoparticles (NP) is one of the most active research fields due to the necessity of robust and, particularly, reproducible methods for the attachment of new biomolecules on the surface. Olefin metathesis offers many of these features, thanks to the new family of catalysts, especially Hoveyda-Grubbs second generation. Iron oxide NP were synthesized by the decomposition of organic precursors obtaining hydrophobic Fe3O4 NP with oleic acid as surfactant. These NP have been functionalized by the use of olefin metathesis reaction with different ligands. The metathesis was performed between the double bond in oleic acid structure and four different molecules with a terminal olefin, methyl acrylate, 6-hexenenitrile, allyltrifluoroacetate and 3-allyloxy-1,2-propandiol, in presence of the catalyst. These new NPs were fully characterized showing the success of the functionalization, small hydrodynamic size, narrow size distribution, and stability in water. This proof of concept opens a new way for the formation of carbon–carbon bonds on the surface of NP for biomedical applications.

The combination of nanoparticles, gene therapy, and medical imaging has given rise to a new field known as gene theranostics, in which a nanobioconjugate is used to diagnose and treat the disease. The process generally involves binding between a vector carrying the genetic information and a nanoparticle, which provides the signal for imaging. The synthesis of this probe generates a synergic effect, enhancing the efficiency of gene transduction and imaging contrast. We discuss the latest approaches in the synthesis of nanoparticles for magnetic resonance imaging, gene therapy strategies, and their conjugation and in vivo application.

The current study presents [(18)F]PARPi as imaging agent for PARP1 expression.[(18)F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[(18)F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma.[(18)F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC50 = 2.8 ± 1.1 nM; logPCHI = 2.15 ± 0.41; plasma-free fraction = 63.9 ± 12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82 ± 0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04 ± 0.01 %ID/g.[(18)F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.

Background Although the understanding of the genetic and molecular basis of cancer has advanced significantly over the past several decades, imaging and treatment options for glioblastoma patients have been more limited (N Engl J Med 359:492-507, 2008). This is in part due to difficulties in diagnosing this disease early, combined with its diffuse, infiltrative growth. This study was aimed at the development of a novel diagnostic tool for glioblastoma through the synthesis of a small molecule based on radioiodinated poly(ADP-ribose)polymerase 1 (PARP1) targeted tracers. This PARP1 is a biomarker that is overexpressed in glioblastoma tissue, but has only low expression levels in the healthy brain (Neoplasia 16:432-40, 2014). Methods A library of PARP1 inhibitors (iodo-PARPis) was synthesized. Based on their pharmacokinetic properties and nuclear PARP1 binding, the most successful inhibitor was radiolabeled with 131I and 124I. Biodistribution as well as imaging experiments were performed in orthotopic and subcutaneous mouse models of glioblastoma. Results One member of our iodo-poly(ADP-ribose)polymerase 1 (PARP1) inhibitor library, I2-PARPi, shows promising biophysical properties for in vivo application. All synthesized tracers have IC50 values in the nanomolar range (9 ± 2–107 ± 4 nM) and were able to inhibit the uptake of a fluorescent PARP1 inhibitor analog (PARPi-FL). I2-PARPi was able to reduce the uptake of PARPi-FL by 78 ± 4 % in vivo. In mouse models of glioblastoma, we show that the radioiodinated inhibitor analog has high uptake in tumor tissue (U251 MG xenograft, tumor, 0.43 ± 0.06 %ID/g; brain, 0.01 ± 0.00 %ID/g; muscle, 0.03 ± 0.01 %ID/g; liver, 2.35 ± 0.57 %ID/g; thyroid, 0.24 ± 0.06 %ID/g). PET and SPECT imaging performed in orthotopic glioblastoma models with [124I]- and [131I]-I2-PARPi showed selective accumulation in the tumor tissue. These results were also verified using autoradiography of tumor sections, which displayed focal selective uptake of the tracer in the tumor regions as confirmed by histology. The uptake could be blocked through pre-injection of excess unlabeled PARP1 inhibitor (Olaparib). Conclusions We have successfully synthesized and radioiodinated the PARP1 selective tracer I2-PARPi. The novel tracer shows selective binding to tumor tissue, both in vitro and in models of glioblastoma, and has the potential to serve as a selective PET imaging agent for brain tumors. Electronic supplementary material The online version of this article (doi:10.1186/s13550-015-0123-1) contains supplementary material, which is available to authorized users.

New intravital optical imaging technologies have revolutionized our understanding of mammalian biology and continue to evolve rapidly. However, there are only a limited number of imaging probes available to date. In this study, we investigated in mouse models of glioblastoma whether a fluorescent small molecule inhibitor of the DNA repair enzyme PARP1, PARPi-FL, can be used as an imaging agent to detect glioblastomas in vivo. We demonstrated that PARPi-FL has appropriate biophysical properties, low toxicity at concentrations used for imaging, high stability in vivo, and accumulates selectively in glioblastomas due to high PARP1 expression. Importantly, subcutaneous and orthotopic glioblastoma xenografts were imaged with high contrast clearly defining tumor tissue from normal surrounding tissue. This research represents a step toward exploring and developing PARPi-FL as an optical intraoperative imaging agent for PARP1 in the clinic.

La libertad de expresión es un derecho que funciona como piedra angular de un Estado democrático, pues permite la toma de decisiones informadas y la transmisión de las ideas. Sin embargo, ese derecho puede encontrar ciertos límites, como el caso de los discursos de odio. En el presente trabajo se analiza cómo deben regularse los límites de la libertad de expresión cuando se trata de discursos de odio, y cuáles deberían ser las sanciones para quienes incurren en dicha conducta.