Immunoliposome-mediated drug delivery to Plasmodium-infected and non-infected red blood cells as a dual therapeutic/prophylactic antimalarial stragegy

One of the most important factors behind resistance evolution in malaria is the failure to deliver sufficiently high amounts of drugs to early stages of Plasmodium-infected red blood cells (pRBCs). Despite having been considered for decades as a promising approach, the delivery of antimalarials encapsulated in immunoliposomes targeted to pRBCs has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here we show that encapsulation efficiencies reaching N96% are achieved for the weak basic drugs chloroquine (CQ) and primaquine using the pH gradient loading method in liposomes containing neutral saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the delivery to the cell of drugs not affecting the erythrocytic metabolism. Using this strategy, we have achieved unprecedented complete nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Immunoliposomes studded with monoclonal antibodies raised against the erythrocyte surface protein glycophorin A were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with N95% of added liposomes retained on cell surfaces. When exposed for only 15 min to Plasmodium falciparum in vitro cultures of early stages, free CQ had no significant effect on the viability of the parasite up to 200 nM, whereas immunoliposomal 50 nM CQ completely arrested its growth. In vivo assays in mice showed that immunoliposomes cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg, whereas free CQ administered at 1.75 mg/kgwas, atmost, 40-fold less efficient. Our data suggest that this significant improvement is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion

Comparativa de conceptes centrals al pensament de Nietzsche i de la tradició budista

De Nietzsche (1844-1900) i el budisme, se n'han fet nombrosos estudis des de diverses aproximacions, amb l'objectiu d'arribar a comprendre la relació del filòsof alemany amb la doctrina de Buda. Aquesta relació és tot sovint contradictòria i construïda des de l'interès i l'admiració, però també des del que sembla ser una òptica equivocada per part del filòsof alemany. Aquest treball fa un recorregut per les primeres aproximacions de Nietzsche al budisme, parant especial atenció a les consideracions que Nietzsche va desenvolupar a través dels seus estudis dels textos budistes. Aquestes es divideixen en tres punts fonamentals: primer, la comparació que Nietzsche va fer entre budisme i cristianisme; segon, la visió del budisme com a una doctrina nihilista; i tercer, la consideració del nirvana com a resultat de la inacció. Partint d'aquests conceptes, es desenvoluparà un estudi comparatiu entre la proposta de Nietzsche i els principis del budismeDe Nietzsche (1844-1900) y el budismo, se han hecho muchos estudios desde diversas aproximaciones, con el objetivo de llegar a comprender la relación del filósofo alemán con la doctrina de Buda. Esta relación es a menudo contradictoria y construida desde el interés y la admiración, pero también desde lo que parece ser una óptica equivocada por parte del filósofo alemán. Este trabajo hace un recorrido por las primeras aproximaciones de Nietzsche hacia budismo, prestando especial atención a las consideraciones que Nietzsche desarrolló a través de sus estudios de los textos budistas. Estas se dividen en tres puntos fundamentales: primero, la comparación que Nietzsche estableció entre budismo y cristianismo; segundo, la visión del budismo como una doctrina nihilista; y tercero, la consideración del nirvana como resultado de la inacción. Partiendo de estos conceptos, se desarrollará un estudio comparativo entre la propuesta de Nietzsche y los principios del budismoThere have been many studies about Nietzsche (1844-1900) and Buddhism that have been created from different approaches, with the aim of understanding the relationship of the German philosopher with the buddhist religion. This relationship is often contradictory and it is built from what appears to be a wrong perspective of Buddhism by the German philosopher. This dissertation takes us through the first thoughts that Nietzsche had about Buddhism, paying particular attention to the considerations that Nietzsche developed through studying Buddhist texts. These considerations are divided into three main points: firstly, the comparison between Buddhism and Christianity; secondly, the vision of Buddhism as a nihilistic doctrine; and thirdly, the idea that nirvana is a result of complete inaction. Taking all these concepts in consideration, a comparative study between Nietzsche's proposal and the principles of Buddhism will be hel

Semaphorin-3F/Neuropilin-2 Transcriptional Expression as a Predictive Biomarker of Occult Lymph Node Metastases in HNSCC

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), A Way to Build Europe; Asociación Española contra el Cáncer (LABAE18025AVIL).The expression of the semaphorin-3F (SEMA3F) and neuropilin-2 (NRP2) is involved in the regulation of lymphangiogenesis. The present study analyzes the relationship between the transcriptional expression of the SEMA3F-NRP2 genes and the presence of occult lymph node metastases in patients with cN0 head and neck squamous cell carcinomas. We analyzed the transcriptional expression of SEMA3F and NRP2 in a cohort of 53 patients with cN0 squamous cell carcinoma treated with an elective neck dissection. Occult lymph node metastases were found in 37.7% of the patients. Patients with occult lymph node metastases (cN0/pN+) had significantly lower SEMA3F expression values than patients without lymph node involvement (cN0/pN0). Considering the expression of the SEMA3F-NRP2 genes, patients were classified into two groups according to the risk of occult nodal metastasis: Group 1 (n = 34), high SEMA3F/low NRP2 expression, with a low risk of occult nodal involvement (14.7% cN0/pN+); Group 2 (n = 19), low SEMA3F or high SEMA3F/high NRP2 expression, with a high risk of occult nodal involvement (78.9% cN0/pN+). Multivariate analysis showed that patients in Group 2 had a 26.2 higher risk of lymph node involvement than patients in Group 1. There was a significant relationship between the transcriptional expression values of the SEMA3F-NRP2 genes and the risk of occult nodal metastases

The snow must go on: Ground ice encasement, snow compaction and absence of snow differently cause soil hypoxia, CO2 accumulation and tree seedling damage in boreal forest

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Protocol d'atenció i acompanyament al naixement a Catalunya

Acompanyament al naixement; Voluntats de la dona; Atenció al nadóBirth support; Women's wills; Newborn careAcompañamiento en el nacimiento; Voluntades de la mujer; Atención al recién nacidoL’Organització Mundial de la Salut, l’any 2018 va proposar una sèrie d’actuacions per a l’atenció al moment del part, que tenen per lema ‘Atenció per a una experiència positiva en el naixement’. En aquest document s’actualitza el ‘Protocol del part, puerperi i atenció al nadó’, document elaborat pel Departament de Salut, publicat l’any 2003 i actualitzat l’any 2019 com a ‘Protocol d’atenció i acompanyament al naixement’, seguint les recomanacions de l’OMS, així com totes aquelles basades en l’evidència científica, amb el màxim respecte a les opinions i voluntats de les dones gestants i amb l’objectiu d’ajudar-les a elles i a les seves famílies a tenir una experiència positiva en el part. Les activitats de promoció de la salut i prevenció de la malaltia són l’eix vertebrador d’aquest protocol i de tots els que es coordinen des del Servei de Salut Maternoinfantil de la Sub-direcció de Promoció de la Salut de l’Agència de Salut Pública de Catalunya del Departament de Salut. En aquest sentit, cal ressaltar la seva relació amb el Protocol del seguiment de l’embaràs a Catalunya (3a. edició) que es va presentar el 2018, amb el qual comparteix principis i enfocament. El protocol s’estructura en tres capítols en relació a les etapes (prepart, part i puerperi), recollint en el tercer, l’atenció la nadó. Cada capítol té diversos apartats en les activitats a realitzar, la informació a donar i el registre, entre d’altres. Es recull, després, la bibliografia i una sèrie de annexos amb eines pràctiques

The HDAC7-TET2 epigenetic axis is essential during early B lymphocyte development

Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2017-87990-R]; Spanish Ministry of Science and Innovation (MICINN) [EUR2019-103835]; Josep Carreras Leukaemia Research Institute (IJC, Badalona, Barcelona); IDIBELL Research Institute (L'Hospitalet de Llobregat, Barcelona); A.M. is funded by the SpanishMinistry of Science, Innovation and Universities, which is part of the Agencia Estatal de Investigación (AEI) [PRE2018- 083183] (cofunded by the European Social Fund]; OdB. was funded by a Juan de la Cierva Formación Fellowship from the Spanish Ministry of Science, Innovation and Universities [FJCI-2017-32430]; Postdoctoral Fellowship from the Asociación Española Contra el Cáncer (AECC) Foundation [POSTD20024DEBA]; B.M. is awardee of the Ayudas para la formación del profesorado universitario [FPU18/00755, Ministerio de Universidades]; B.M.J. is funded by La Caixa Banking Foundation Junior Leader project [LCF/BQ/PI19/11690001]; FEDER/SpanishMinistry of Science and Innovation [RTI2018-094788-A-I00]; L.T.-D. is funded by the FPI Fellowship [PRE2019- 088005]; L.R. is funded by an AGAUR FI fellowship [2019FI-B00017]; J.L.S. is funded by ISCIII [CP19/00176], co-funded by ESF, 'Investing in your future' and the Spanish Ministry of Science, Innovation and Universities [PID2019-111243RA-I00]. CRG acknowledge the support of the SpanishMinistry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049- S, MCIN/AEI /10.13039/501100011033). Funding for open access charge: Spanish Ministry of Science, Innovation and Universities (MICIU) [SAF2017-87990-R, EUR2019-103835].Correct B cell identity at each stage of cellular differentiation during B lymphocyte development is critically dependent on a tightly controlled epigenomic landscape. We previously identified HDAC7 as an essential regulator of early B cell development and its absence leads to a drastic block at the pro-B to pre-B cell transition. More recently, we demonstrated that HDAC7 loss in pro-B-ALL in infants associates with a worse prognosis. Here we delineate the molecular mechanisms by which HDAC7 modulates early B cell development. We find that HDAC7 deficiency drives global chromatin de-condensation, histone marks deposition and deregulates other epigenetic regulators and mobile elements. Specifically, the absence of HDAC7 induces TET2 expression, which promotes DNA 5-hydroxymethylation and chromatin de-condensation. HDAC7 deficiency also results in the aberrant expression of microRNAs and LINE-1 transposable elements. These findings shed light on the mechanisms by which HDAC7 loss or misregulation may lead to B cell-based hematological malignancies