Microplásticos en mejillones silvestres (Mytilus spp.) de la costa del norte de España

Microplastic content (MPs) in mussels (Mytilus spp.) from two areas of the north coast of Spain was measured for the first time. Additionally, a comparison of microplastic levels observed in mussels digested with nitric acid and with potassium hydroxide was carried out. The average microplastic concentration in mussels digested with nitric acid was significantly lower than that observed in mussels digested with potassium hydroxide (p < 0.05). The average concentration of microplastics in mussels from the Cantabrian Sea (2.55±2.80 MPs g–1 WW) was slightly higher than that in mussels from the Ria of Vigo (1.59±1.28 MPs g–1 WW). Both in the Ria of Vigo and in the Cantabrian Sea the observed pattern of pollution was fitted to the one expected. Consequently, mussels have been confirmed as suitable sentinel organisms for microplastic pollution.Se midió por primera vez el contenido en microplásticos (MPs) presente en mejillones (Mytilus spp.) procedentes de dos áreas de la costa del norte de España. Además, se llevó a cabo una comparación de los niveles de microplásticos observados en mejillones digeridos con ácido nítrico y con hidróxido de potasio. La concentración promedio de microplásticos que se observó en los mejillones digeridos con ácido nítrico fue significativamente inferior a la observada en los mejillones digeridos con hidróxido de potasio (

Critical experiments with albendazole in the treatment of protostrongylid infection of sheep

p. 543-553El trabajo da a conocer los resultados de una experiencia crítica con 60 ovejas. Divididas en 3 lotes: G-1 testigos; G-2 tratadas con una sola dosis de 10 mg/kg de peso vivo de ABZ; G-3, tratadas con dos dosis de 7,5 mg/kgN

Antileishmanial activity of terpenylquinones on Leishmania infantum and their effects on Leishmania topoisomerase IB

[EN] Leishmania is the aethiological agent responsible for the visceral leishmaniasis, a serious parasite-borne disease widely spread all over the World. The emergence of resistant strains makes classical treatments less effective; therefore, new and better drugs are necessary. Naphthoquinones are interesting compounds for which many pharmacological properties have been described, including leishmanicidal activity. This work shows the antileishmanial effect of two series of terpenyl-1,4-naphthoquinones (NQ) and 1,4-anthraquinones (AQ) obtained from natural terpenoids, such as myrcene and myrceocommunic acid. They were evaluated both in vitro and ex vivo against the transgenic iRFP-Leishmania infantum strain and also tested on liver HepG2 cells to determine their selectivity indexes. The results indicated that NQ derivatives showed better antileishmanial activity than AQ analogues, and among them, compounds with a diacetylated hydroquinone moiety provided better results than their corresponding quinones. Regarding the terpenic precursor, compounds obtained from the monoterpenoid myrcene displayed good antiparasitic efficiency and low cytotoxicity for mammalian cells, whereas those derived from the diterpenoid showed better antileishmanial activity without selectivity. In order to explore their mechanism of action, all the compounds have been tested as potential inhibitors of Leishmania type IB DNA topoisomerases, but only some compounds that displayed the quinone ring were able to inhibit the recombinant enzyme in vitro. This fact together with the docking studies performed on LTopIB suggested the existence of another mechanism of action, alternative or complementary to LTopIB inhibition. In silico druglikeness and ADME evaluation of the best leishmanicidal compounds has shown good predictable druggabilitySIFinancial support came from Spanish MINECO (CTQ2015-68175-R, AGL2016-79813-C2-1-R, AGL2016-79813-C2-2-R and SAF2017-83575-R), ISCIII-RICET Network (RD12/0018/0002) and Consejería de Educación de la Junta de Castilla y León (LE020P17) co-financed by the Fondo Social Europeo of the European Union (FEDER-EU). P. G. J. acknowledges funding by Fundación Salamanca Ciudad de Cultura y Saberes (’‘Programme for attracting scientific talent to Salamanca’‘

Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review

The aim of this paper was to review the available evidence on the efficacy and safety of combined or sequential use of PD-1/PD-L1 immune checkpoint inhibitors (ICI) and CAR-T cell therapies in relapsed/refractory (R/R) haematological malignancies. A systematic literature review was performed until 21 November 2022. Inclusion criteria: cohort studies/clinical trials aimed at evaluating the efficacy and/or safety of the combination of CAR-T cell therapy with PD-1/PD-L1 inhibitors in R/R haematological malignancies, which had reported results. Those focusing only on ICI or CAR-T separately or evaluating the combination in other non-hematological solid tumours were excluded. We used a specific checklist for quality assessment of the studies, and then we extracted data on efficacy or efficiency and safety. A total of 1867 articles were identified, and 9 articles were finally included (early phase studies, with small samples of patients and acceptable quality). The main pathologies were B-cell acute lymphoblastic leukaemia (B-ALL) and B-cell non-Hodgkin’s lymphoma (B-NHL). The most studied combination was tisagenlecleucel with pembrolizumab. In terms of efficacy, there is great variability: the combination could be a promising option in B-ALL, with modest data, and in B-NHL, although hopeful responses were received, the combination does not appear better than CAR-T cell monotherapy. The safety profile could be considered comparable to that described for CAR-T cell monotherapy

Changes in toxin content, biomass and pigments of the dinoflagellate Alexandrium minutum during nitrogen refeeding and growth into nitrogen or phosphorus stress

Two strains oi the paralytic shellfish toxin (PST) producing dinoflagellate Alexandrium minutum Halim (highly toxic ALl V and weakly toxic AL2V) were grown in batch culture with either nitrate or phosphate as the limiting nutrient. In comparison with cells of the strain AL1V, cells of AL2V grew at a similar C-specific Tale, had a higher C/N ratio, and lower ratios of chl a/chl C2and chl a/peridinin. Neither chlorophylls flor carotenoids could be used to estimate C-biomass, N-biomass or toxin content for this organismo The toxin profile for both strains was dominated (up to 95 %) by the gonyautoxin GTX4, with smaller proportions of GTX1, GTX2 and GTX3. The Tale of toxin synthesis for both strains was greatest 1 to 2 d after the N-refeeding of N-deprived cells, with the net Tale of toxin syn- .thesis exceeding that of C-biomass and cell division by a factor of up to 4. Toxin synthesis was not enhanced by short-term P-stress. N-stress alone led to a decrease in toxin cell-I, but P-stress followed by N-stress did not result in such a decline, implicating phosphorus in the regulation of toxin metabolism. Although arginine is a majar precursor for PST synthesis, taurine, glycine, glutamine, and cell N showed similar relations to that observed for arginine with respect to toxin contento Furthermore, the mole ratio of arginine/toxin could vary by a factor of up to 5 between AL1V and AL2V at peak values of toxin cell-1, and by more than 5 within a strain when growing under different conditions. These observations suggest that the relationship between free arginine content and toxin content is complex. No explanation for the higher toxin content of AL1V is apparent, except that AL1V has a higher N-content per cell and this may be conducive to a higher Tale of synthesis of the N-rich toxins.Publicado

The interplay between mechanics and stability of viral cages

The stability and strength of viral nanoparticles are crucial to fulfill the functions required through the viral cycle as well as using capsids for biomedical and nanotechnological applications. The mechanical properties of viral shells obtained through Atomic Force Microscopy (AFM) and continuum elasticity theory, such as stiffness or Young's modulus, have been interpreted very often in terms of stability. However, viruses are normally subjected to chemical rather than to mechanical aggression. Thus, a correct interpretation of mechanics in terms of stability requires an adequate linkage between the ability of viral cages to support chemical and mechanical stresses. Here we study the mechanical fragility and chemical stability of bacteriophage T7 in two different maturation states: the early proheads and the final mature capsids. Using chemical stress experiments we show that proheads are less stable than final mature capsids. Still, both particles present similar anisotropic stiffness, indicating that a continuum elasticity description in terms of Young's modulus is not an adequate measure of viral stability. In combination with a computational coarse-grained model we demonstrate that mechanical anisotropy of T7 emerges out of the discrete nature of the proheads and empty capsids. Even though they present the same stiffness, proheads break earlier and have fractures ten times larger than mature capsids, in agreement with chemical stability, thus demonstrating that fragility rather than stiffness is a better indicator of viral cages' stabilityWe acknowledge funding by grants from the Ministry of Science and Innovation of Spain, PIB2010US-00233, FIS2011-29493 and Consolider CSD2010-00024 (to P.J.P.), FIS2011-22603 and FIS2011-16090-E (D.R.), BFU2011-29038 (to J.L.C.), BFU2011-25902 (to J.R.C.) and the Comunidad de Madrid no. S2009/MAT-1467 (to P.J.P.) and S2009/MAT-1507 (to J.L.C.) We are grateful to M. García-Mateu (UAM), Julio Gómez-Herrero (UAM) and Red Española Interdisciplinar de Biofísica de los Virus (BioFiViNet), FIS2011-16090-E for expert technical help

Biophysical properties of single rotavirus particles account for the functions of protein shells in a multilayered virus

The functions performed by the concentric shells of multilayered dsRNA viruses require specific protein interactions that can be directly explored through their mechanical properties. We studied the stiffness, breaking force, critical strain and mechanical fatigue of individual Triple, Double and Single layered rotavirus (RV) particles. Our results, in combination with Finite Element simulations, demonstrate that the mechanics of the external layer provides the resistance needed to counteract the stringent conditions of extracellular media. Our experiments, in combination with electrostatic analyses, reveal a strong interaction between the two outer layers and how it is suppressed by the removal of calcium ions, a key step for transcription initiation. The intermediate layer presents weak hydrophobic interactions with the inner layer that allow the assembly and favor the conformational dynamics needed for transcription. Our work shows how the biophysical properties of the three shells are finely tuned to produce an infective RV virio

Adenovirus major core protein condenses DNA in clusters and bundles, modulating genome release and capsid internal pressure

Some viruses package dsDNA together with large amounts of positively charged proteins, thought to help condense the genome inside the capsid with no evidence. Further, this role is not clear because these viruses have typically lower packing fractions than viruses encapsidating naked dsDNA. In addition, it has recently been shown that the major adenovirus condensing protein (polypeptide VII) is dispensable for genome encapsidation. Here, we study the morphology and mechanics of adenovirus particles with (Ad5-wt) and without (Ad5-VII-) protein VII. Ad5-VII- particles are stiffer than Ad5-wt, but DNA-counterions revert this difference, indicating that VII screens repulsive DNA-DNA interactions. Consequently, its absence results in increased internal pressure. The core is slightly more ordered in the absence of VII and diffuses faster out of Ad5-VII- than Ad5-wt fractured particles. In Ad5-wt unpacked cores, dsDNA associates in bundles interspersed with VII-DNA clusters. These results indicate that protein VII condenses the adenovirus genome by combining direct clustering and promotion of bridging by other core proteins. This condensation modulates the virion internal pressure and DNA release from disrupted particles, which could be crucial to keep the genome protected inside the semi-disrupted capsid while traveling to the nuclear pore

Clinical and immunological study of tofacitinib and baricitinib in refractory blau syndrome: case report and literature review

Blau syndrome (BS) is an autoinflammatory disorder characterized by non-caseating granulomatous dermatitis, arthritis, and uveitis. We present a case of refractory and severe BS that was treated with the Janus kinase inhibitors (JAKINIBS), Tofacitinib (TOFA) and then Baricitinib (BARI). Our aim was to describe the clinical and immunological outcomes after treatment with JAKINIBS. Blood tests and serum samples were obtained during follow-up with TOFA and BARI. We assessed their effects on clinical outcomes, acute phase reactants, absolute lymphocyte counts (ALCs), lymphocyte subset counts, immunoglobulins, and cytokine levels. A review of the literature on the use of JAKINIBS for the treatment of uveitis and sarcoidosis was also conducted. TOFA led to a rapid and maintained disease control and a steroid-sparing effect. A decrease from baseline was observed in ALC, CD3+, CD4+, CD8+, and natural killer (NK) cell counts. B-cells were stable. Serum levels of interleukin (IL)-4 and tumor necrosis factor alpha (TNF-?) increased, whereas IL-2, IL-6, IL-10, and IL-17 maintained stable. TOFA was discontinued after 19 months due to significant lymphopenia. The initiation of BARI allowed maintaining adequate control of disease activity with an adequate safety profile. The literature review showed seven patients with uveitis and five with sarcoidosis treated with JAKINIBS. No cases of BS treated with JAKINIBS were found. We report the successful use of JAKINIBS in a patient with refractory and severe BS.Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was partially supported by Redes Temáticas de Investigación Cooperativa en Salud (RETICS) Program, RD16/0012 Red de Investigación en Inflamación y Enfermedades Reumáticas (RIER) from ISCIII from "Instituto de Salud Carlos III" (ISCIII) (Spain)