Evaluation of New Formulations of Antihelmintic Drugs for the Treatment of Schistosomiasis

La esquistosomosis es una enfermedad causada por parásitos trematodos del género Schistosoma. Afecta principalmente a áreas tropicales y subtropicales, siendo un principal problema de salud mundial por su alta incidencia en estas regiones. Una de las especies de mayor importancia, por su prevalencia y gravedad, es la causada por Schistosoma mansoni,responsable de la esquistosomosis intestinal. El tratamiento de elección esel praziquantel, con altas tasas de eficacia clínica. Sin embargo, el fármacono impide la reinfección y se ha observado fallos terapéuticos en zonasendémicas. Por ello, se hace necesaria la búsqueda de alternativas terapéuticas.El objetivo de este estudio es evaluar dos tipos de formulaciones denanopartículas de praziquantel (tipo A y tipo S) y un tratamiento alternativocomo la ivermectina mediante ensayos in vitro sobre adultos de S. mansoni.Los resultados demostraron que el tratamiento con nanopartículas presentauna eficacia similar o mayor que el empleo de praziquantel comercial. Sinembargo, el tratamiento con ivermectina no aportó evidencias de mayoreficacia. Trabajos futuros irán encaminados a evaluar estas formulacionesen otras fases del ciclo biológico, así como a realizar estudios in vivo enanimales de experimentación.Palabras clave: Schistosoma; esquistosomosis; praziquantel; nanopartículas;ivermectina.Fil: Castrillejo, Sergio A.. Universidad de Salamanca; EspañaFil: López Abán, Julio. Universidad de Salamanca; EspañaFil: Muro, Antonio. Universidad de Salamanca; EspañaFil: Salomon, Claudio Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Pastor Navarro, Marta. Universidad del País Vasco; España. Centro de Investigación Biomédica en Red; EspañaFil: Pedraz, José Luis. Universidad del País Vasco; España. Centro de Investigación Biomédica en Red; Españ

Microscopic approach to the response of 3 - 4 He mixtures

Correlated-basis-function perturbation theory is used to evaluate the zero-temperature response S(q,¿) of 3-4He mixtures for inelastic neutron scattering, at momentum transfers q ranging from 1.1 to 1.8 A°-1. We adopt a Jastrow correlated ground state and a basis of correlated particle-hole and phonon states. We insert correlated one-particle–one-hole and one- and two-phonon states to compute the second-order response. The decay of the one-phonon states into two-phonon states is accounted for in the boson-boson approximation. The full response is split into three partial components Saß(q,¿), each of them showing a particle-hole bump and a one phonon, d-shaped peak, which stays separated from the multiphonon background. The cross term S34(q,¿) results to be of comparable importance to S33(q,¿) in the particle-hole sector and to S44(q,¿) in the phonon one. Once the response has been convoluted with the experimental broadening, the computed scattering function is in semiquantitative agreement with recent experimental measurements.Postprint (published version

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in Spain, among population targeted for vaccination

Background: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed 4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season

Progress in loop-mediated isothermal amplification assay for detection of Schistosoma mansoni DNA: towards a ready-to-use test

[ENG]Schistosomiasis is one of the most prevalent Neglected Tropical Disease, affecting approximately 250 million people worldwide. Schistosoma mansoni is the most important species causing human intestinal schistosomiasis. Despite significant efforts in recent decades, the global disease burden of schistosomiasis remains extremely high. This could partly be attributed to the absence of accurate diagnostic tools, primarily in endemic areas. Loop-mediated isothermal amplification (LAMP) is increasingly used in molecular diagnostics as a field-friendly alternative to many other complex molecular methods and it has been proposed as an ideal candidate for revolutionizing point-of-care molecular diagnostics. In a previous work, a LAMP-based method to detect S. mansoni DNA (SmMIT-LAMP) was developed by our research group for early diagnosis of active schistosomiasis in an experimental infection murine model. The SmMIT-LAMP has been further successfully evaluated in both human stool and snail samples and, recently, in human urine samples. In this study, we developed an important improvement for SmMIT-LAMP molecular assay, transforming it into a cold maintenance dry format suitable for potentially manufacturing as kit for ready-to-use for schistosomiasis diagnosis. This procedure could be applied to create dry LAMP kits for a laboratory setting and for diagnostic applications for other neglected tropical diseases

Mechanisms of dissolved and labile particulate iron supply to shelf waters and phytoplankton blooms off South Georgia, Southern Ocean

The island of South Georgia is situated in the iron (Fe)-depleted Antarctic Circumpolar Current of the Southern Ocean. Iron emanating from its shelf system fuels large phytoplankton blooms downstream of the island, but the actual supply mechanisms are unclear. To address this, we present an inventory of Fe, manganese (Mn), and aluminium (Al) in shelf sediments, pore waters, and the water column in the vicinity of South Georgia, alongside data on zooplankton-mediated Fe cycling processes, and provide estimates of the relative dissolved Fe (DFe) fluxes from these sources. Seafloor sediments, modified by authigenic Fe precipitation, were the main particulate Fe source to shelf bottom waters as indicated by the similar Fe∕Mn and Fe∕Al ratios for shelf sediments and suspended particles in the water column. Less than 1% of the total particulate Fe pool was leachable surface-adsorbed (labile) Fe and therefore potentially available to organisms. Pore waters formed the primary DFe source to shelf bottom waters, supplying 0.1–44µmolDFem−2d−1. However, we estimate that only 0.41±0.26µmolDFem−2d−1 was transferred to the surface mixed layer by vertical diffusive and advective mixing. Other trace metal sources to surface waters included glacial flour released by melting glaciers and via zooplankton egestion and excretion processes. On average 6.5±8.2µmolm−2d−1 of labile particulate Fe was supplied to the surface mixed layer via faecal pellets formed by Antarctic krill (Euphausia superba), with a further 1.1±2.2µmolDFem−2d−1 released directly by the krill. The faecal pellets released by krill included seafloor-derived lithogenic and authigenic material and settled algal debris, in addition to freshly ingested suspended phytoplankton cells. The Fe requirement of the phytoplankton blooms  ∼  1250km downstream of South Georgia was estimated as 0.33±0.11µmolm−2d−1, with the DFe supply by horizontal/vertical mixing, deep winter mixing, and aeolian dust estimated as  ∼ 0.12µmolm−2d−1. We hypothesize that a substantial contribution of DFe was provided through recycling of biogenically stored Fe following luxury Fe uptake by phytoplankton on the Fe-rich shelf. This process would allow Fe to be retained in the surface mixed layer of waters downstream of South Georgia through continuous recycling and biological uptake, supplying the large downstream phytoplankton blooms

Considerations for COVID-19 management in reception centers for refugees, asylum seekers, and migrants, Spain 2020

Shortly after the declaration of the COVID-19 pandemic, governments around the world were urged to leave no population behind. Following a COVID-19 risk evaluation in a refugee and asylum seekers reception center, in September 2020, we considered the priorities of managing COVID-19 in these settings. We encourage actions on four fronts to reduce the COVID-19 associated burden amongst these vulnerable populations based on our interviews, observations and recommendations: (i) decongestion, (ii) facilitated testing, (iii) screening for symptoms and (iv) targeted public health and risk communication.S

F.J. Clemens and Some Aspects of Neo-Scholasticism in the Education of F. Brentano

Among the few publications which consider the Scholastic roots of Brentano’s thinking, an article by Dieter Münch stands out. In it, he claims that the Aristotelian studies of Brentano and his whole philosophical project are inspired by the German Neo-Scholastic movement. Münch presents the Neo-Scholastic tendency as an ultra-conservative and reactionary program against modernity. Now, such a description makes almost inexplicable the fact that Brentano, who was educated in this context, could have developed a wholly personal and independent philosophy. To approach this framework objectively, I propose to pay attention to F.J. Clemens, a Neo-Scholastic who influenced Brentano’s way of thinking. It is true that Clemens puts faith above reason and affirms that any conclusion obtained through the power of reason must be discarded when it contradicts faith. However, this is not an ultramontane innovation but simply the traditional theological point of view. He also argues that St. Thomas should be followed as a guide to orient oneself in the process of rational inquiry. Nevertheless, he doesn’t want to understand philosophy as a repetition of Aquinas’ claims; on the contrary, he rather proposes an intelligent use of tradition, which allows us to delve deeper into philosophical truth. For this very reason, he does not discard modernity or condemn it altogether. This perspective is also reflected in the early writings of Brentano, where he showed discontinuity from the Neo-Scholastic school of thought

Introduction to the French GEOTRACES North Atlantic transect (GA01): GEOVIDE cruise

© 2018 Author(s). The GEOVIDE cruise, a collaborative project within the framework of the international GEOTRACES programme, was conducted along the French-led section in the North Atlantic Ocean (Section GA01), between 15 May and 30 June 2014. In this special issue (https://www.biogeosciences.net/special-issue900.html), results from GEOVIDE, including physical oceanography and trace element and isotope cyclings, are presented among 18 articles. Here, the scientific context, project objectives, and scientific strategy of GEOVIDE are provided, along with an overview of the main results from the articles published in the special issue

Synthesis of Structurally Related Coumarin Derivatives as Antiproliferative Agents

A library of structurally related coumarins was generated through synthesis reactions and chemical modification reactions to obtain derivatives with antiproliferative activity both in vivo and in vitro. Out of a total of 35 structurally related coumarin derivatives, seven of them showed inhibitory activity in in vitro tests against Taq DNA polymerase with IC50 values lower than 250 μM. The derivatives 4-(chloromethyl)-5,7-dihydroxy-2H-chromen-2-one (2d) and 4-((acetylthio)methyl)-2-oxo-2H-chromen-7-yl acetate (3c) showed the most promising anti-polymerase activity with IC50 values of 20.7 ± 2.10 and 48.25 ± 1.20 μM, respectively. Assays with tumor cell lines (HEK 293 and HCT-116) were carried out, and the derivative 4-(chloromethyl)-7,8-dihydroxy-2H-chromen-2-one (2c) was the most promising, with an IC50 value of 8.47 μM and a selectivity index of 1.87. In addition, the derivatives were evaluated against Saccharomyces cerevisiae strains that report about common modes of actions, including DNA damage, that are expected for agents that cause replicative stress. The coumarin derivatives 7-(2-(oxiran-2-yl)ethoxy)-2H-chromen-2-one (5b) and 7-(3-(oxiran-2-yl)propoxy)-2H-chromen-2-one (5c) caused DNA damage in S. cerevisiae. The O-alkenylepoxy group stands out as that with the most important functionality within this family of 35 derivatives, presenting a very good profile as an antiproliferative scaffold. Finally, the in vitro antiretroviral capacity was tested through RT-PCR assays. Derivative 5c showed inhibitory activity below 150 μM with an IC50 value of 134.22 ± 2.37 μM, highlighting the O-butylepoxy group as the functionalization responsible for the activity.This research was supported by CONICET (PIP 11220200101091CO 2021-2023), PICT 2017-0785 Type D of the National Agency for Scientific and Technological Promotion, UNSL (PROICO 02-2620), and RGLP from AvH Foundation. E.F.B.-H. thanks CONICET for doctoral fellowship and specially to Graphic Designer Bruna-Haupt L. for his help. H.A.G. thanks CONICET for belonging to the CIC. We wish thank to Dr. Di Marco N. I. for the genetic material gently provided. C.R.P. thanks CONICET for belonging to the CIC and Alexander von Humboldt Foundation for the different subsidies. We appreciate language revision by staff from the Instituto de Lenguas, UNSL, and specially Mg. Rezzano S.F.M. thanks to the Spanish Ministry of Science (research grant BFU2017-83954-R), ACIISI (research grant ProID2017010167), and FIISC (research grant PIFIIS19/04). C.G. thanks Ministerio de Ciencia, Innovación y Universidades (MCIU) of Spain-European Regional Development Fund (ERDF) (PGC2018-094503-B-C22). This work is a part of the cotutelled (UNSL-ULL) Ph.D. of E.F.B.-H.Peer reviewe