Anxiety and mild microglial activation in the amygdala two weeks after NA-induced neuroinflammation

A single injection of neuraminidase (NA) within the cerebral ventricles (ICV) triggers an acute neuroinflammation. Neurological complications or behavioral alterations have been associated to neuroinflammation. While some of these symptoms decline with time along with inflammation, the possibility of long-term sequelae should be considered. Thus, we aimed to explore if NA-induced neuroinflammation provokes behavioral or neurological disturbances at medium (2 weeks) and long (10 weeks) term. Rats were ICV injected with NA or saline. First, neurological alterations of the sensorimotor reflexes were not found, suggesting that NA does not cause disturbances in major brain functions. While the open field test revealed normal locomotor capacity in the animals injected with NA, however the evaluation of specific behaviors (rearing and rearing with support) pointed out an increased anxiety state 2 weeks after NA administration, but not at long term (10 weeks). A histological study of brain areas related to emotions (amygdala) and stress response (hypothalamic PVN) revealed no significant differences in the number of microglia or astrocytes. Nevertheless, the morphological analysis of microglial cells demonstrated that, in the amygdala of NA injected rats, microglia presented a morphology consistent with a slightly activated state. Such morphological change, which was evident 2 weeks after NA injection, was virtually reverted 10 weeks post-ICV. These results point out that NA injected ICV may cause anxiety in the medium term (while not affecting other functions like sensorimotor functions or the locomotor capacity), a behavioral alteration that is transient and that concurs with a mild inflammation, evidenced by the overexpression of certain genes and, more notably, by the morphological bias of microglial cells located in the amygdala towards an activated profile.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Apicultura Argentina: contexto fundacional y elementos de resiliencia del sector

La apicultura en la Argentina se inició a mediados del siglo XIX con la introducción de un número pequeño de colmenas de Apis mellifera L. en eventos puntuales e históricamente registrados. El mito fundacional enuncia que proliferaron dada la abundancia de flora silvestre. El desarrollo técnico de la cadena de valor se potenció en las primeras décadas del siglo XX, apoyado por actores definidos, que convirtieron al sector en uno de los principales proveedores de miel en el mercado internacional. Adversidades sanitarias y alteraciones en las condiciones ambientales debidas, principalmente, a cambios en el uso de la tierra que condicionan la apicultura a escala global han tenido un impacto importante. Las estrategias desarrolladas en los sectores de investigación y desarrollo, su extensión y adopción por productores deseosos de continuar en la apicultura han permitido la resiliencia frente a diferentes crisis.Beekeeping in Argentina began in the middle of the 19th century with the introduction of a small number of hives of Apis mellifera L. in specific and historically recorded events. The founding myth states that they proliferated due to the abundance of wild flora. The technical development of the value chain was strengthened in the first decades of the 20th century, supported by defined actors, which led the sector to become one of the main suppliers of honey in the international market. Sanitary adversities and alterations in the environment mainly due to changes in land use, which condition beekeeping on a global scale, have had a significant impact. The strategies developed in the research and development sectors, their extension and adoption by producers eager to continue in beekeeping have allowed resilience in the face of different crises.EEA Delta del ParanáFil: Basilio, Alicia Mabel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; ArgentinaFil: Lopez, Valeria Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Delta del Paraná; Argentina.Fil: Lopez, Valeria Carolina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; ArgentinaFil: Landi, Lucas. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; ArgentinaFil: Landi, Lucas. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; ArgentinaFil: Mellado, Lorena M. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; ArgentinaFil: Pedraza, Facundo. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; ArgentinaFil: Molina, Gonzalo Alberto Roman. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; ArgentinaFil: Gurini, Laura Beatriz. Profesional independiente. Programa Apícola Nacional PROAPI-INTA; Argentin

EP05.02-002 Who Benefits More of Durvalumab after Chemoradiotherapy (CRT) in Real-World Patients with Locally Advanced Non-Small-Cell Lung Cancer (NSCLC)?

[EN] Introduction: Durvalumab received EMA approval as consolidation therapy (CT) for unresectable stage III NSCLC with PD-L1 _1% and who did not have progression after CRT. Our objective was to analyze in real clinical practice the effectiveness of durvalumab and explore the clinical factors that may be associated with the benefit from CT. Methods: Retrospective study was made at Hospital of Leon (Spain), including 37 patients with locally advanced NSCLC treated with durvalumab after CRT treatment between March 2018 and october 2021 (40.5% patients were included in the durvalumab early access program). The neutrophil-to-lymphocyte ratio (NLR) could identified after CRT as a factor that may be benefit from durvalumab. Results: Median age was 67 years (range 46-82 years). 40.5% of patients were _70 years old. 78.4% were male and 51.4% smokers. 54% had non-squamous histology. PD-L1 expression was <1% in 5% and not available in 8% patients. 2.7% ROS1 rearrangements, 5.4% KRAS mutations and not available in 43.2% patients. Stage IIIA, IIIB, IIIC disease were 24.3%, 54.1% and 21.6%, respectively. Median time from end of CRT to onset durvalumab was 44 days (range 13-120 days). Overall median CT duration was 214.8 days (range 69-399 days) with a median of 14 infusions (range 6-27 infusions). With a median follow up of 19.7 months (range 1.4-34.9 months); 67.6% had stopped CT: 37.8% due to completing treatment, 16.2% disease progression, 10.8% adverse event and 2.7% due to COVID19 infection. Median real-world progressionfree survival (rwPFS) was 17 months (95% CI, 11-23). Median realworld overall survival (rwOS) was 29.9 months (95% CI, 23.3-36.6). % rwOS at 6, 18 and 24 months were 100%, 86.9% and 74.5%, respectively. For patients with post-CRT NLR not exceeding the cohort median value of 6, receipt of durvalumab was associated with an improvement in rwOS (median not reached vs 25.7 months; p¼0.025). 56.8% patients had any grade of radiation pneumonitis (median time from CRT start: 119 days [range 36-241 days]). Of these, 19% patients developed worsening of radiation pneumonitis with durvalumab. 54,1% developed immune-mediated toxicity, mostly G1-2 (85.1%). Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation in this patients population in a real-life setting. We identified low NLR after CRT as a potentially predictive factor for the benefit of CT in locally advanced NSCLC.S

EP05.02-003 Durvalumab after Chemoradiotherapy (CRT) in Unresectable Stage III NSCLC. Comparative Study of Two Cohorts in the Real-World Setting

[EN] Introduction: Durvalumab is the new standard of care for unresectable locally advanced NSCLC, with PD-L1 _1% and who did not have progression after CRT treatment in the European Union. Our study compares the effectiveness and the frequency of radiation pneumonitis in patients treated with concurrent CRT with or without durvalumab consolidation during the same period in real clinical practice. Methods: A single-center retrospective study. 71 treated patients with unresectable stage III NSCLC were included between March 2018 and December 2021, 37 with CRT followed by durvalumab and 34 with CRT alone. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were calculated since the date of the end CRT. Propensity score matching (PSM) 1:1 was used to account for differences in baseline characteristics. Results: Median age was 67 years (range 46-82). 25.4% of the patients were _75 years old. 78.9% were men and 53.5% former smokers. 54.9% had squamous histology and 28%, 51% and 21% stage IIIA, IIIB and IIIC disease, respectively. The most used scheme was carboplatinpaclitaxel (43.7%), receiving induction chemotherapy in up to 54.9% of patients. 73.2% received between 60-66 Gy doses of radiotherapy. Median time from end of CRT to onset durvalumab was 44 days (range 13-120) with a median of 14 infusions (range 6-27). Of the 34 patients without durvalumab treatment, the expression PD-L1 <1% (58.8%) was the most frequent cause for rejecting consolidation therapy. After PSM analysis, patients distributions were well balanced. With a median follow-up of 19.7 months (range 1.4-36.6); median rw-PFS was 9.3 months (95% CI, 5-13.5) without durvalumab and 17 months (95% CI, 11-22.9) with durvalumab (p¼0.013). Median rw-OS was 19.3 months (95% CI, 3.8-34.8) without durvalumab and 29.9 months (95% CI, 23.3-36.6) with durvalumab (p¼0.241) with a rw-OS% at 6, 18 and 24 months of 90%, 62% and 49% vs 100%, 86% and 74%, respectively. The rate of radiation pneumonitis was more frequent with durvalumab consolidation (56.8% against 44.1%), (p¼0.346), especially within 3 months after CRT. G3 pneumonitis was only observed in the consolidation therapy. Conclusions: Our results demonstrate the effectiveness of durvalumab consolidation after CRT in real-world patients with unresectable stage III NSCLC. Further sample and longer follow-up are required to obtain more accurate results. Active surveillance and appropriate management for radiation pneumonitis are needed, in especially in candidates for consolidation treatmentS

El proceso de fermentación en la producción artesanal de hidromiel y su evaluación sensorial

En el hidromiel confluyen las ideas de alimentación natural y saludable relacionadas con la miel, con las de un producto artesanal y gourmet. La oferta de este producto se está expandiendo en las ferias regionales de todo el país pero, a pesar de la mención en la literatura de ficción, el producto es desconocido en el mercado local y comienza a fabricarse con bajos volúmenes y a ofrecerse con calidad dispar. Los objetivos de este trabajo fueron: 1) evaluar y comparar las cepas de levaduras disponibles en el mercado en cuanto a la eficiencia del proceso y a la calidad sensorial del producto, y 2) brindar parámetros accesibles a los productores sobre la evolución de la fermentación en diferentes concentraciones de mosto. Para ello, se evaluaron tratamientos con cuatro cepas de Saccharomyces en tres concentraciones diferentes de mosto. Además, se registró la evolución de la fermentación, y se elaboraron curvas que permitirán al productor artesanal estimar la situación de sus fermentados de miel con mediciones simples. Los productos se sometieron a dos instancias de evaluación hedónica: por consumidores (n≈200), y por un panel semi entrenado (n=10). El 93% de los consumidores no conocía la existencia de la bebida, y el 83% la encontró aceptable en relación a sus expectativas. Los consumidores que habían probado hidromiel opinaron que el degustado era satisfactorio, sin poder discriminar entre variedades; mientras que el panel de expertos sólo detectó olores y sabores en los hidromieles secos.Mead reflects the convergence of the concepts of natural and healthy food, in terms of honey, with the concepts of a hand-made and gourmet product. The offer of mead is expanding in regional markets throughout the country, and, although it is mentioned in the fictional literature, the mead remains unknown in the local market. It is currently being manufactured in low volumes and offered with unequal quality. The objectives of this study were: 1) to evaluate and compare the quality of the yeast available in the market in terms of process efficiency and the product’s sensory quality; and 2) to provide accessible parameters of the fermentation evolution to the producers in different concentrations of must. Treatments with four strains of Saccharomyces in three different concentrations of must were evaluated. The evolution of the fermentation was recorded, and curves that will enable honey fermentation process follow-up were built. The products were subjected to two instances of hedonic evaluation: by consumers (n≈200), and by a semitrained tasting panel (n=10). 93% of the consumers did not know about the existence of the drink, and the 83% of them found it acceptable in relation to their expectations. Consumers who had tried mead before considered that the taste was satisfactory, although they were not able to discriminate between varieties, while the panel of experts found off odors and flavors only in the dry mead.EEA Delta del ParanáFil: Basilio, Alicia Mabel. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal, Cátedra de Avicultura, Cunicultura y Apicultura; y Departamento de Biología Aplicada y Alimentos; ArgentinaFil: Prieto, José E. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Microbiología Agrícola; ArgentinaFil: Lopez, Valeria Carolina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Delta del Paraná; Argentina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal, Cátedra de Avicultura, Cunicultura y Apicultura; y Departamento de Biología Aplicada y Alimentos; ArgentinaFil: Mellado, Lorena M. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal, Cátedra de Avicultura, Cunicultura y Apicultura; y Departamento de Biología Aplicada y Alimentos; ArgentinaFil: Pascual, Graciela. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; y Departamento de Biología Aplicada y Alimentos; ArgentinaFil: Pedraza, Facundo. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; y Departamento de Biología Aplicada y Alimentos; ArgentinaFil: Fráncica, Karina. Universidad de Buenos Aires. Facultad de Agronomía. Departamento de Producción Animal. Cátedra de Avicultura, Cunicultura y Apicultura; y Departamento de Biología Aplicada y Alimentos; ArgentinaFil: Alvarez, Raul. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Delta del Paraná; ArgentinaFil: Gurini, Laura Beatriz. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Delta del Paraná; Argentin

Approaches to mixture risk assessment of PFASs in the European population based on human hazard and biomonitoring data

Per- and polyfluoroalkyl substances (PFASs) are a highly persistent, mobile, and bioaccumulative class of chemicals, of which emissions into the environment result in long-lasting contamination with high probability for causing adverse effects to human health and the environment. Within the European Biomonitoring Initiative HBM4EU, samples and data were collected in a harmonized way from human biomonitoring (HBM) studies in Europe to derive current exposure data across a geographic spread. We performed mixture risk assessments based on recent internal exposure data of PFASs in European teenagers generated in the HBM4EU Aligned Studies (dataset with N = 1957, sampling years 2014-2021). Mixture risk assessments were performed based on three hazard-based approaches: the Hazard Index (HI) approach, the sum value approach as used by the European Food Safety Authority (EFSA) and the Relative Potency Factor (RPF) approach. The HI approach resulted in the highest risk estimates, followed by the RPF approach and the sum value approach. The assessments indicate that PFAS exposure may result in a health risk in a considerable fraction of individuals in the HBM4EU teenager study sample, thereby confirming the conclusion drawn in the recent EFSA scientific opinion. This study underlines that HBM data are of added value in assessing the health risks of aggregate and cumulative exposure to PFASs, as such data are able to reflect exposure from different sources and via different routes.This work was supported by the European Union’s Horizon 2020 research and innovation programme under Grant agreement No 733032 HBM4EU (www.HBM4EU.eu), and received co-funding from the au thors’ organizations. The Norwegian Institute of Public Health (NIPH) has contributed to funding of the Norwegian Environmental Biobank (NEB), and the laboratory measurements have partly been funded by the Research Council of Norway through research projects (275903 and 268465). The PCB cohort (follow-up) received additional funding from the Ministry of Health of the Slovak Republic (program 07B0103).S

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells

The induction of interferon beta (IFNB1) is a key event in the antiviral immune response. We studied the role of transcriptional noise in the regulation of the IFNB1 locus in primary cultures of human dendritic cells (DCs), which are important ‘first responders’ to viral infection. In single cell assays, IFNB1 mRNA expression in virus-infected DCs showed much greater cell-to-cell variation than that of a housekeeping gene, another induced transcript and viral RNA. We determined the contribution of intrinsic noise by measuring the allelic origin of transcripts in each cell and found that intrinsic noise is a very significant part of total noise. We developed a stochastic model to investigate the underlying mechanisms. We propose that the surprisingly high levels of IFNB1 transcript noise originate from the complexity of IFNB1 enhanceosome formation, which leads to a range up to many minutes in the differences within each cell in the time of activation of each allele

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13