Multiscale model for the effects of adaptive immunity suppression on the viral therapy of cancer

Oncolytic virotherapy - the use of viruses that specifically kill tumor cells - is an innovative and highly promising route for treating cancer. However, its therapeutic outcomes are mainly impaired by the host immune response to the viral infection. In the present work, we propose a multiscale mathematical model to study how the immune response interferes with the viral oncolytic activity. The model assumes that cytotoxic T cells can induce apoptosis in infected cancer cells and that free viruses can be inactivated by neutralizing antibodies or cleared at a constant rate by the innate immune response. Our simulations suggest that reprogramming the immune microenvironment in tumors could substantially enhance the oncolytic virotherapy in immune-competent hosts. Viable routes to such reprogramming are either in situ virus-mediated impairing of CD$8^+$ T cells motility or blockade of B and T lymphocytes recruitment. Our theoretical results can shed light on the design of viral vectors or new protocols with neat potential impacts on the clinical practice.Comment: 14 pages, 4 figure

Controversy-seeking fuels rumor-telling activity in polarized opinion networks

Rumors have ignited revolutions, undermined the trust in political parties, or threatened the stability of human societies. Such destructive potential has been significantly enhanced by the development of on-line social networks. Several theoretical and computational studies have been devoted to understanding the dynamics and to control rumor spreading. In the present work, a model of rumor-telling in opinion polarized networks was investigated through extensive computer simulations. The key mechanism is the coupling between ones' opinions and their leaning to spread a given information, either by supporting or opposing its content. We report that a highly modular topology of polarized networks strongly impairs rumor spreading, but the couplings between agent's opinions and their spreading/stifling rates can either further inhibit or, conversely, foster information propagation, depending on the nature of those couplings. In particular, a controversy-seeking mechanism, in which agents are stimulated to postpone their transitions to the stiffer state upon interactions with other agents of confronting opinions, enhances the rumor spreading. Therefore such a mechanism is capable of overcoming the propagation bottlenecks imposed by loosely connected modular structures.Comment: 11 pages, 7 figure

Planning process for an operational management platform for a public transport

This work addresses the planning process of a public passenger transport operator, including the generation of schedules and services for vehicles and drivers, in the framework of a previously agreed service. This problem will be studied in the context of all stages of the planning process: parameterization, preparation, production of performance indicators and the generation of results for different operational scenarios.info:eu-repo/semantics/publishedVersio

Planning process for an operational management platform for a public transport

This work addresses the planning process of a public passenger transport operator, including the generation of schedules and services for vehicles and drivers, in the framework of a previously agreed service. This problem will be studied in the context of all stages of the planning process: parameterization, preparation, production of performance indicators and the generation of results for different operational scenarios.info:eu-repo/semantics/publishedVersio

Risk Factors for Perioperative Complications in Endoscopic Surgery with Irrigation

AbstractBackground and objectivesCurrently, endoscopic medicine is being increasingly used, albeit not without risks. Therefore, this study evaluated the factors associated with perioperative complications in endoscopic surgery with intraoperative irrigation.MethodA cohort study of six months duration. Patients aged ≥ 18 years undergoing endoscopic surgery with the use of irrigation fluids during the intraoperative period were included. Exclusion criteria were: use of diuretics, kidney failure, cognitive impairment, hyponatremia prior to surgery, pregnancy, and critically ill. The patients who presented with or without complications during the perioperative period were allocated into two groups. Complications evaluated were related to neurological, cardiovascular and renal changes, and perioperative bleeding.ResultsIn total, 181 patients were enrolled and 39 excluded; therefore, 142 patients met the study criteria. Patients with complications amounted to 21.8%, with higher prevalence in endoscopic prostate surgery, followed by hysteroscopy, bladder, knee, and shoulder arthroscopy (58.1%, 36.9%, 19.4%, 3.8%, 3.2% respectively). When comparing both groups, we found association with complications in univariate analysis: age, sex, smoking, heart disease, ASA, serum sodium at the end of surgery, total irrigation fluid administered, TURP, and hysteroscopy. However, in multiple regression analysis for complications, only age (OR = 1.048), serum sodium (OR = 0.962), and volume of irrigation fluid administered during surgery (OR = 1.001) were independent variables

Molecular investigation of isolates from a multistate polymicrobial outbreak associated with contaminated total parenteral nutrition in Brazil

Background: Between November 2013 and June 2014, 56 cases of bacteremia (15 deaths) associated with the use of Total Parenteral Nutrition (TPN) and/or calcium gluconate (CG) were reported in four Brazilian states. Methods: We analyzed 73 bacterial isolates from four states: 45 from blood, 25 from TPN and three from CG, originally identified as Acinetobacter baumannii, Rhizobium radiobacter, Pantoea sp. or Enterobacteriaceae using molecular methods. Results: The first two bacterial species were confirmed while the third group of species could not be identified using standard identification protocols. These isolates were subsequently identified by Multi-Locus Sequence Analysis as Phytobacter diazotrophicus, a species related to strains from similar outbreaks in the United States in the 1970’s. Within each species, TPN and blood isolates proved to be clonal, whereas the R. radiobacter isolates retrieved from CG were found to be unrelated. Conclusion: This is the first report of a three-species outbreak caused by TPN contaminated with A. baumannii, R. radiobacter and P. diazotrophicus. The concomitant presence of clonal A. baumannii and P. diazotrophicus isolates in several TPN and blood samples, as well as the case of one patient, where all three different species were isolated simultaneously, suggest that the outbreak may be ascribed to a discrete contamination of TPN. In addition, this study highlights the clinical relevance of P. diazotrophicus, which has been involved in outbreaks in the past, but was often misidentified as P. agglomerans

Loxosceles gaucho spider venom and its sphingomyelinase fraction trigger the main functions of human and rabbit platelets

Loxosceles venoms can promote severe local and systemic damages. We have previously reported that Loxosceles gaucho spider venom causes a severe early thrombocytopenia in rabbits. Herein, we investigated the in vitro effects of this venom and its sphingomyelinase fraction on the main functions of platelets. Whole venom and its fraction induced aggregation of both human and rabbit platelets. Aggregation was dependent of plasma component(s) but independent of venom-induced lysophosphatidic acid generation. There was no increase in the levels of lactate dehydrogenase during platelet aggregation, ruling out the possibility of platelet lysis. The increased expression of ligand-induced binding site 1 (LIBS1) induced by L. gaucho venom and its sphingomyelinase fraction, as well as of P-selectin by the whole venom, evidenced the activation state of both human and rabbit platelets. Adhesion assays showed an irregular response when platelets were exposed to the whole venom, whereas the sphingomyelinase fraction induced a dose-dependent increase in the platelet adhesion to collagen. These findings evidence that L. gaucho venom and its sphingomyelinase fraction trigger adhesion, activation, and aggregation of both human and rabbit platelets. Thus, this work justifies the use of rabbits to investigate Loxosceles venom-induced platelet disturbances, and it also supports research on the role of platelets in the pathogenesis of loxoscelism.Fil: Tavares, Flávio L.. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Peichoto, María Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; ArgentinaFil: Rangel, Danieli de Morais. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Barbaro, Kátia Cristina. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Cirillo, Maria Cristina. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Santoro, Marcelo Larami. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; BrasilFil: Sano Martins, Ida S.. Governo do Estado de Sao Paulo. Secretaria da Saude. Instituto Butantan; Brasi

Protective Response Mechanisms to Heat Stress in Interaction with High [CO2] Conditions in Coffea spp.

This work was supported by national funds from Fundacao para a Ciencia e a Tecnologia through the projects PTDC/AGRPRO/3386/2012, the research units UID/AGR/04129/2013 (LEAF) and UID/GEO/04035/2013 (GeoBioTcc), as well through the grant SFRH/BPD/47563/2008 (AT) co-financed through the POPH program subsidized by the European Social Fund. Brazilian funding from CAPES (grams PDSE: 000427/2014-04, W.P. Rodrigues; 0343/2014-05, MM; 12226/12-2, LM), CNPq and Fapemig (fellowships to FDM, FP, and EC) are also greatly acknowledged.Modeling studies have predicted that coffee crop will be endangered by future global warming, but recent reports highlighted that high [CO2] can mitigate heat impacts on coffee. This work aimed at identifying heat protective mechanisms promoted by CO2 in Coffea arabica (cv. Icatu and IPR108) and Coffea canephora cv. Conilon CL153. Plants were grown at 25/20 degrees C (day/night), under 380 or 700 mu L CO2 L-1, and then gradually submitted to 31/25, 37/30, and 42/34 degrees C. Relevant heat tolerance up to 37/30 degrees C for both [CO2] and all coffee genotypes was observed, likely supported by the maintenance or increase of the pools of several protective molecules (neoxanthin, lutein, carotenes, ohtocopherol, HSP70, raffinose), activities of antioxidant enzymes, such as superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), catalase (CAT), and the upregulated expression of some genes (ELIP, Chaperonin 20). However, at 42/34 degrees C a tolerance threshold was reached, mostly in the 380 -plants and Icatu. Adjustments in raffinose, lutein, beta-carotene, alpha-tocopherol and HSP70 pools, and the upregulated expression of genes related to protective (FLIPS, HSP70, Chape 20, and 60) and antioxidant (CAT, CuSOD2, APX Cyt, APX ChI) proteins were largely driven by temperature. However, enhanced [CO2] maintained higher activities of GR (Icatu) and CAT (Icatu and IPR108), kept (or even increased) the Cu,Zn-SOD, APX, and CAT activities, and promoted a greater upregulation of those enzyme genes, as well as those related to HSP70, ELIPs, Chaperonins in CL153, and Icatu. These changes likely favored the maintenance of reactive oxygen species (ROS) at controlled levels and contributed to mitigate of photosystem II photoinhibition at the highest temperature. Overall, our results highlighted the important role of enhanced [CO2] on the coffee crop acclimation and sustainability under predicted future global warming scenarios.publishersversionpublishe

The first observed stellar occultations by the irregular satellite Phoebe (Saturn IX) and improved rotational period

peer reviewedWe report six stellar occultations by Phoebe (Saturn IX), an irregular satellite of Saturn, obtained between mid-2017 and mid-2019. The 2017 July 6 event was the first stellar occultation by an irregular satellite ever observed. The occultation chords were compared to a 3D shape model of the satellite obtained from Cassini observations. The rotation period available in the literature led to a sub-observer point at the moment of the observed occultations where the chords could not fit the 3D model. A procedure was developed to identify the correct sub-observer longitude. It allowed us to obtain the rotation period with improved precision compared to the currently known value from literature. We show that the difference between the observed and the predicted sub-observer longitude suggests two possible solutions for the rotation period. By comparing these values with recently observed rotational light curves and single- chord stellar occultations, we can identify the best solution for Phoebe's rotational period as 9.27365 ± 0.00002 h. From the stellar occultations, we also obtained six geocentric astrometric positions in the ICRS as realized by the Gaia DR2 with uncertainties at the 1-mas level