Toxicidade dérmica e oftálmica do extrato hidroalcoholico de Curcuma longa, Linn (Curcuvet) em modelos in vivo

Transforming medicinal plants into industrializable and marketable products involves meeting numerous regulatory requirements regarding the quality, safety, efficacy and stability of the proposed formulation. In this context, the product Curcuvet (antiseptic and healing solution obtained from the hydroalcoholic extract of C. longa) needs to demonstrate its safety before being legally used in veterinary clinical practice. Therefore, the present work aimed to evaluate in vivo the dermal and ophthalmic toxic potentialities of the product. To achieve this, three in vivo investigations were carried out: acute dermal toxicity, primary dermal irritancy and ophthalmic irritancy according to the standards described by the Organization for Economic Cooperation and Development (OECD) No. 434, 404 and 405, respectively. The Curcuvet product in all tests was administered as a single dose, superficially on both skin (Sprague Dawley rat and F1 rabbits) and ocular mucosa (New Zealand albino rabbits). The Curcuvet product was not irritating to the skin of rats and rabbits, but not to the ocular structures, which were severely damaged, reaching an irritancy index of 110. It is concluded that the Curcuvet formulation, administered in single dose, was not a dermal irritant and a severe ophthalmic irritant.Transformar las plantas medicinales en productos industrializables y comercializables implica cumplir numerosas exigencias regulatorias, sobre calidad, seguridad, eficacia y estabilidad de la formulación propuesta. En este contexto, el producto Curcuvet (solución antiséptica y cicatrizante obtenida a partir del extracto hidroalcohólico de C. longa) necesita demostrar su inocuidad antes de utilizarse legalmente en la práctica clínica veterinaria. Por tanto, el presente trabajo tuvo como objetivo evaluar in vivo las potencialidades tóxicas dérmica y oftálmica del producto. Para lograrlo se realizaron tres investigaciones in vivo: toxicidad aguda dérmica, irritabilidad dérmica primaria e irritabilidad oftálmica según las normas descritas por la Organización para la Cooperación Económica y el Desarrollo (OECD) No. 434, 404 y 405 respectivamente. El producto Curcuvet en todos los ensayos fue administrado en dosis única, de forma superficial tanto en piel (rata Sprague Dawley y conejos F1) como en mucosa ocular (conejos albinos Nueva Zelanda). El producto Curcuvet no resultó irritante para la piel de ratas y conejos, no así para las estructuras oculares, las cuales fueron severamente dañadas, alcanzándose un índice de irritabilidad de 110. Se concluye que la formulación Curcuvet administrado en dosis única, resultó no irritante dérmico e irritante severo oftálmico.A transformação de plantas medicinais em produtos industrializáveis e comercializáveis envolve o cumprimento de inúmeros requisitos regulamentares sobre qualidade, segurança, eficácia e estabilidade da formulação proposta. Neste contexto, o produto Curcuvet (uma solução anti-séptica e curativa obtida a partir do extrato hidroalcoólico de C. longa) precisa demonstrar sua segurança antes de poder ser legalmente utilizado na prática clínica veterinária. Portanto, o presente trabalho visou avaliar o potencial tóxico dérmico e oftálmico do produto in vivo. Para isso, foram realizadas três investigações in vivo: toxicidade dérmica aguda, irritação dérmica primária e irritação oftalmológica de acordo com as normas descritas pela Organização para Cooperação e Desenvolvimento Econômico (OCDE) No. 434, 404 e 405, respectivamente. O curcuvet em todos os testes foi administrado como dose única, superficialmente tanto à pele (rato Sprague Dawley e coelhos F1) quanto à mucosa ocular (coelhos albinos da Nova Zelândia). O Curcuvet não era irritante para a pele de ratos e coelhos, mas não para as estruturas oculares, que estavam gravemente danificadas, atingindo um índice de irritação de 110. Conclui-se que a formulação Curcuvet, administrada em doses únicas, era não-irritante para a pele e severamente irritante para a mucosa oftálmica

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Anuario del Centro de Estudios Martianos (Vol. 25 2002)

El Anuario del Centro de Estudios Martianos es la publicación insignia de esta institución y heredera directa del Anuario Martiano de la Biblioteca Nacional José Martí, que se publicó entre 1969 y 1977, bajo la dirección del poeta y ensayista Cintio Vitier.<br> Desde que salió a la luz su primera entrega, en 1978, se han publicado treinta y cinco números, en los que aparecen artículos y ensayos de importantes estudiosos de la vida y obra del Apóstol, en Cuba y el resto del mundo.<br> En sus secciones fijas (Otros textos de José Martí, Documentos, Estudios y aproximaciones, Vigencias, Publicaciones, Bibliografía, Constante) y los apartados especiales, los lectores pueden conocer disímiles temas del quehacer martiano internacional, en el año que termina además de mantenerse al tanto de las últimas contribuciones de los promotores e investigadores de la obra martiana en el orbe

Novel genes and sex differences in COVID-19 severity.

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided

Investigation of K+K− interactions via femtoscopy in Pb-Pb collisions at √sNN = 2.76 TeV at the CERN Large Hadron Collider

Femtoscopic correlations of non-identical charged kaons (K+K−) are studied in Pb−Pb collisions at a center-of-mass energy per nucleon−nucleon collision sNN−−−√=2.76 TeV by ALICE at the LHC. One-dimensional K+K− correlation functions are analyzed in three centrality classes and eight intervals of particle-pair transverse momentum. The Lednický and Luboshitz interaction model used in the K+K− analysis includes the final-state Coulomb interactions between kaons and the final-state interaction through a0(980) and f0(980) resonances. The mass of f0(980) and coupling were extracted from the fit to K+K− correlation functions using the femtoscopic technique for the first time. The measured mass and width of the f0(980) resonance are consistent with other published measurements. The height of the ϕ(1020) meson peak present in the K+K− correlation function rapidly decreases with increasing source radius, qualitatively in agreement with an inverse volume dependence. A phenomenological fit to this trend suggests that the ϕ(1020) meson yield is dominated by particles produced directly from the hadronization of the system. The small fraction subsequently produced by FSI could not be precisely quantified with data presented in this paper and will be assessed in future work

Two-particle transverse momentum correlations in pp and p-Pb collisions at energies available at the CERN Large Hadron Collider

Two-particle transverse momentum differential correlators, recently measured in Pb-Pb collisions at LHC energies, provide an additional tool to gain insights into particle production mechanisms and infer transport properties, such as the ratio of shear viscosity to entropy density, of the medium created in Pb-Pb collisions. The longitudinal long-range correlations and the large azimuthal anisotropy measured at low transverse momenta in small collision systems, namely pp and p-Pb, at LHC energies resemble manifestations of collective behaviour. This suggests that locally equilibrated matter may be produced in these small collision systems, similar to what is observed in Pb-Pb collisions. In this work, the same two-particle transverse momentum differential correlators are exploited in pp and p-Pb collisions at s√=7 TeV and sNN−−−√=5.02 TeV, respectively, to seek evidence for viscous effects. Specifically, the strength and shape of the correlators are studied as a function of the produced particle multiplicity to identify evidence for longitudinal broadening that might reveal the presence of viscous effects in these smaller systems. The measured correlators and their evolution from pp and p-Pb to Pb-Pb collisions are additionally compared to predictions from Monte Carlo event generators, and the potential presence of viscous effects is discussed

Measurement of the production cross section of prompt Ξ0c baryons in p–Pb collisions at √sNN = 5.02 TeV

The transverse momentum (pT) differential production cross section of the promptly-produced charm-strange baryon Ξ0c (and its charge conjugate Ξ0c¯¯¯¯¯¯) is measured at midrapidity via its hadronic decay into π+Ξ− in p−Pb collisions at a centre-of-mass energy per nucleon−nucleon collision sNN−−−√ = 5.02 TeV with the ALICE detector at the LHC. The Ξ0c nuclear modification factor (RpPb), calculated from the cross sections in pp and p−Pb collisions, is presented and compared with the RpPb of Λ+c baryons. The ratios between the pT-differential production cross section of Ξ0c baryons and those of D0 mesons and Λ+c baryons are also reported and compared with results at forward and backward rapidity from the LHCb Collaboration. The measurements of the production cross section of prompt Ξ0c baryons are compared with a model based on perturbative QCD calculations of charm-quark production cross sections, which includes only cold nuclear matter effects in p−Pb collisions, and underestimates the measurement by a factor of about 50. This discrepancy is reduced when the data is compared with a model in which hadronisation is implemented via quark coalescence. The pT-integrated cross section of prompt Ξ0c-baryon production at midrapidity extrapolated down to pT = 0 is also reported. These measurements offer insights and constraints for theoretical calculations of the hadronisation process. Additionally, they provide inputs for the calculation of the charm production cross section in p−Pb collisions at midrapidity

Measurement of Ω0c baryon production and branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) in pp collisions at √s = 13 TeV

The inclusive production of the charm-strange baryon Ω0c is measured for the first time via its semileptonic decay into Ω−e+νe at midrapidity (|y| < 0.8) in proton–proton (pp) collisions at the centre-of-mass energy √s = 13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 < pT < 12 GeV/c. The branching-fraction ratio BR(Ω0c → Ω−e+νe)/BR(Ω0c → Ω−π+) is measured to be 1.12 ± 0.22 (stat.) ± 0.27 (syst.). Comparisons with other experimental measurements, as well as with theoretical calculations, are presented