The ever more frequent utilisation of culture for political and economic purposes has increasingly stretched the meaning of the word, ultimately watering down its identification with an elite ...practice to the more contemporary sense of entertainment and leisure. This article attempts to analyse this process in 19th-century Spain through a notable event—the crowning of Zorilla. The crowning of José Zorrilla as poet laureate in June 1889 marked his instatement in the role of intellectual touchstone for Restoration Spain, as the creator of a kind of sentimental nationalism that sat well with conservative ways of thinking that made myths of an idealised past. Like all the other commemorations and centenaries celebrated in the late 19th and early 20th centuries, this event was part of a tendency of liberal states to instrumentalise culture, which although not new was an early forerunner of contemporary political strategies.
La cada vez más frecuente instrumentalización de la cultura con fines políticos y económicos ha ido incrementando la plasticidad del significado del término para diluir su identidad como práctica de ...una elite hasta el concepto más contemporáneo de espectáculo y ocio. El presente artículo trata de analizar este proceso en la España del siglo xix a través de un acontecimiento como fue la coronación de Zorrilla. La coronación de José Zorrilla como poeta nacional en junio de 1889 supuso la consagración del poeta como referente intelectual de la España de la Restauración en tanto que creador de un nacionalismo sentimental que se adecuaba a los parámetros conservadores que mitificaban un pasado idealizado. Este acto cultural, al igual que las conmemoraciones y centenarios celebrados entre finales del siglo xix y principios del xx, forma parte de un uso instrumental de la cultura por parte de los estados liberales que, sin ser algo novedoso, anunciaba ya estrategias políticas contemporáneas.
The treatment of some high-incidence human diseases is based on therapeutic cell killing. In cancer this is mainly achieved by chemical drugs that are systemically administered to reach effective ...toxic doses. As an innovative alternative, cytotoxic proteins identified in nature can be adapted as precise therapeutic agents. For example, individual toxins and venom components, proapoptotic factors, and antimicrobial peptides from bacteria, animals, plants, and humans have been engineered as highly potent drugs. In addition to the intrinsic cytotoxic activities of these constructs, their biological fabrication by DNA recombination allows the recruitment, in single pharmacological entities, of diverse functions of clinical interest such as specific cell-surface receptor binding, self-activation, and self-assembling as nanoparticulate materials, with wide applicability in cell-targeted oncotherapy and theragnosis.
Targeting cytotoxic drugs in oncology is essential because side toxicities limit reaching effective local doses.
Functionalization of nanoscale drug vehicles has so far achieved a moderate targeting effect. The nanoscale size of drug preparations favors enhanced permeability and retention (EPR) and reduces renal filtration.
Proteins are used as inert nanoscale carriers and as functional targeting agents in the form of antibodies or ligands that bind to tumor cell-surface markers.
Many protein species exhibit potent cytotoxic activities that have been exploited to develop new antitumor drugs.
Protein engineering and recombinant DNA technologies allow cytotoxic proteins to be empowered with accessory domains for oligomerization, targeting, endosomal escape, and self-activation. Therefore, the production of self-assembling, self-delivered protein drugs for oncology is becoming feasible.
Under the unmet need of efficient tumor‐targeting drugs for oncology, a recombinant version of the plant toxin ricin (the modular protein T22‐mRTA‐H6) is engineered to self‐assemble as protein‐only, ...CXCR4‐targeted nanoparticles. The soluble version of the construct self‐organizes as regular 11 nm planar entities that are highly cytotoxic in cultured CXCR4+ cancer cells upon short time exposure, with a determined IC50 in the nanomolar order of magnitude. The chemical inhibition of CXCR4 binding sites in exposed cells results in a dramatic reduction of the cytotoxic potency, proving the receptor‐dependent mechanism of cytotoxicity. The insoluble version of T22‐mRTA‐H6 is, contrarily, moderately active, indicating that free, nanostructured protein is the optimal drug form. In animal models of acute myeloid leukemia, T22‐mRTA‐H6 nanoparticles show an impressive and highly selective therapeutic effect, dramatically reducing the leukemia cells affectation of clinically relevant organs. Functionalized T22‐mRTA‐H6 nanoparticles are then promising prototypes of chemically homogeneous, highly potent antitumor nanostructured toxins for precise oncotherapies based on self‐mediated intracellular drug delivery.
One of the most potent protein toxins in nature, ricin, is genetically instructed to self‐assemble as 11 nm homomeric nanoparticles that selectively kill CXCR4‐overexpressing cells. These materials show a potent antitumoral effect when administered to an animal model of the difficult‐to‐treat disseminated acute myeloid leukemia, in complete absence of side toxicity.
Objetive
To address the prevalence of SARS-CoV-2 and the evolutionary profile of immune compounds in breastmilk of positive mothers according to time and disease state.
Methods
Forty-five women with ...term pregnancies with confirmed non-severe SARS-CoV-2 infection (case group), and 96 SARS-CoV-2 negative women in identical conditions (control group) were approached, using consecutive sample. Weekly (1st to 5th week postpartum) reverse transcription polymerase chain reaction (RT-PCR) in nasopharyngeal swabs (cases) and breastmilk (cases and controls) were obtained. Concentration of cytokines, chemokines, and growth factors in breastmilk (cases and controls) were determined at 1st and 5th week post-partum.
Results
Thirty-seven (study group) and 45 (control group) women were enrolled. Symptomatic infection occurred in 56.8% of women in the study group (48% fever, 48% anosmia, 43% cough). SARS-CoV-2 RNA was not found in breastmilk samples. Concentrations of cytokines (IFN-γ, IL-1ra, IL-4, IL-6, IL-9, IL-13, and TNF-α) chemokines (eotaxin, IP-10, MIP-1α, and RANTES) and growth factors (FGF, GM-CSF, IL7, and PDGF-BB) were higher in breastmilk of the study compared with the control group at 1st week postpartum. Immune compounds concentrations decreased on time, particularly in the control group milk samples. Time of nasopharyngeal swab to become negative influenced the immune compound concentration pattern. Severity of disease (symptomatic or asymptomatic infection) did not affect the immunological profile in breast milk.
Conclusions
This study confirms no viral RNA and a distinct immunological profile in breastmilk according to mother’s SARS-CoV-2 status. Additional studies should address whether these findings indicate efficient reaction against SARS-CoV-2 infection, which might be suitable to protect the recipient child.
Background
Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC ...and to identify predictors of remission to ADA.
Methods
This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response.
Results
We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission.
Conclusions
In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.
To assess the impact of SARS-CoV-2 viral infection on the metataxonomic profile and its evolution during the first month of lactation.
Milk samples from 37 women with full-term pregnancies and mild ...SARS-CoV-2 infection and from 63 controls, collected in the first and fifth postpartum weeks, have been analyzed. SARS-CoV-2 RNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) both in cases and controls. After DNA extraction, the V3-V4 hypervariable region of the gene 16S rRNA was amplified and sequenced using the MiSeq system of Illumina. Data were submitted for statistical and bioinformatics analyses after quality control.
All the 1st week and 5th week postpartum milk samples were negative for SARS-CoV-2 RNA. Alpha diversity showed no differences between milk samples from the study and control group, and this condition was maintained along the observation time. Analysis of the beta-diversity also indicated that the study and control groups did not show distinct bacterial profiles.
and
were the most abundant genera and the only ones that were detected in all the milk samples provided. Disease state (symptomatic or asymptomatic infection) did not affect the metataxonomic profile in breast milk.
These results support that in the non-severe SARS-CoV-2 pregnant woman infection the structure of the bacterial population is preserved and does not negatively impact on the human milk microbiota.
La documentation latine conservée dans la Péninsule semble accréditer l’idée d’une profonde rupture entre un septième siècle très normatif, continuant l’Antiquité, et un dixième siècle pleinement ...médiéval, dominé par la coutume : alors que l’époque wisigothique nous transmet de nombreux textes juridiques, les royaumes chrétiens du Nord demeurent pendant longtemps dépourvus de toute nouvelle législation, séculière ou ecclésiastique. Pourtant, le risque est grand pour l’historien de voir cette incontestable distorsion se transformer en un mirage, d’autant plus séduisant qu’il valorise la rupture de 711 : mirage d’un monde antique dominé par le droit positif et opposé à un univers médiéval étranger à la chose juridique. En relisant des sources très diverses, ce dossier considère le droit comme une donnée vivante, plurielle et toujours au cœur des enjeux sociétaux. La documentación latina conservada en la Península Ibérica parece acreditar la idea de una ruptura profunda entre un siglo vii muy normativo, que continúa la Antigüedad, y un siglo x plenamente medieval, dominado por la costumbre: mientras que la época visigoda nos transmitió numerosos textos jurídicos, los reinos cristianos del Norte permanecieron por largo tiempo privados de toda nueva legislación, secular o eclesiástica. Sin embargo, el historiador se arriesga a ver esa distorsión transformarse en un espejismo, que es tanto más seductor si valoriza la ruptura de 711: espejismo de un mundo antiguo, dominado por el derecho positivo y opuesto a un universo medieval ajeno al jus. Releyendo fuentes muy variadas, este dossier estudia el derecho como un dato vivo, plural y en interacción con la sociedad. The Latin documentation preserved in the Iberian Peninsula appears to reflect a profound break between the seventh century, characterised by the prevalence of law, a continuation of Antiquity, and the entirely mediaeval tenth century, ruled by custom. While the Visigothic age bequeathed numerous legal statutes, the Christian kingdoms of the north were long bereft of any legislation, be it secular or ecclesiastic. Nonetheless, historians are at risk of misinterpreting what is undeniably a distortion—all the more tempting in light of the break that took place in 711—and accepting the vision of an ancient world governed by positive law in opposition to a mediaeval world alien to the rule of law. This dossier returns to sources of widely-varying natures, approaching the law as a living, manifold entity, aever at the heart of society’s vital interests.
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