Inflammation: The Link between Neural and Vascular Impairment in the Diabetic Retina and Therapeutic Implications

Diabetic retinopathy; Inflammation; RetinaRetinopatia diabètica; Inflamació; RetinaRetinopatía diabética; Inflamación; RetinaThe etiology of diabetic retinopathy (DR) is complex, multifactorial and compromises all the elements of the retinal neurovascular unit (NVU). This diabetic complication has a chronic low-grade inflammatory component involving multiple inflammatory mediators and adhesion molecules. The diabetic milieu promotes reactive gliosis, pro-inflammatory cytokine production and leukocyte recruitment, which contribute to the disruption of the blood retinal barrier. The understanding and the continuous research of the mechanisms behind the strong inflammatory component of the disease allows the design of new therapeutic strategies to address this unmet medical need. In this context, the aim of this review article is to recapitulate the latest research on the role of inflammation in DR and to discuss the efficacy of currently administered anti-inflammatory treatments and those still under development.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects ICI20/00129 and PI22/01670 and co-funded by the European Union. Hugo Ramos is the recipient of a grant from the Ministerio de Economía y Competitividad (BES-2017-081690)

Three dimensional modeling and ecological characterization of beaches with Posidonia oceanica beach wrack: examples of Southeast Spain

Los arribazones de Posidonia oceanica se acumulan en las playas del mar Mediterráneo, formando una barrera protectora entre la interfase mar-tierra. Dicha barrera protege a la playa de la pérdida de arena, suponiendo un aporte de nutrientes al complejo arenoso y permitiendo la estructuración de la macrofauna de invertebrados, que encuentran alimento y protección en ellos. Debido al dinamismo de las playas de arena y de los arribazones, resulta necesario establecer modelos costeros que integren a los arribazones como elemento clave. En este trabajo se muestra la integración de estas estructuras en el modelo costero desarrollado, empleando para ello la técnica basada en instrumentación LIDAR, que ha permitido proponer una metodología para evaluar las variaciones de arena ganadas y perdidas a lo largo de diversas campañas de estudio, teniendo como elemento clave a la estructura de los arribazones. Por otro lado, la permanencia a largo plazo de los arribazones permite una estructuración gradual de la fauna de invertebrados de las playas de arena. En este estudio, se compararon dos playas, una con los arribazones retirados por maquinaria pesada y otra no, mostrando diferencias significativas con mayor abundancia de ejemplares la playa en la que los arribazones no fueron removidos por maquinaria. El orden Amphipoda fue el más abundante en las inmediaciones de los arribazones, y el orden Coleoptera en el estrato supralitoral. Se desprende que la conservación de los arribazones permite una recuperación rápida del entorno.Posidonia oceanica “banquettes” accumulate on the beaches of the Mediterranean Sea, forming a protective barrier between the sea-land interface. This barrier protects the beach from the loss of sand, besides supposing a nutrient contribution to the sandy complex, allowing the structure of the macrofauna of coastal invertebrates, which in addition to finding food, obtain shelter and protection in them. Due to the dynamism of the sandy beaches and the “banquettes”, it is necessary to establish study methodologies that integrate this beach-cast accumulation as a key element. This work shows the integration of these structures in the coastal model developed, using the technique based on LIDAR instrumentation, which have allowed us to propose a methodology to evaluate the variations of sand, taking as a key element to structure of the cliffs. On the other hand, the long-term permanence of dead leaves allows a gradual structuring of the invertebrate fauna in sandy beaches. In this work, two beaches were compared, one subjected to cleaning process by heavy machinery, and another in which it remained unpolluted during the study period, showing significant differences with greater abundance of specimens the beach which the cliffs were not removed. The order Amphipoda was the most abundant in the vicinity of the beach-cast accumulations, and the order Coleoptera in the supralittoral zone. It is evident that the conservation of the “banquettes” allows a quick recovery of the surroundings.Este trabajo se ha realizado en el marco del proyecto de investigaciones emergentes de la Universidad de Alicante (GRE14-05), en colaboración con el CIMAR (Centro de Investigación Marina) y el Ayuntamiento de Santa Pola

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

Model-Independent Observation of Exotic Contributions to B0→J/ψK+π−B^0\to J/\psi K^+\pi^- Decays

International audienceAn angular analysis of B0→J/ψK+π- decays is performed, using proton-proton collision data corresponding to an integrated luminosity of 3  fb-1 collected with the LHCb detector. The m(K+π-) spectrum is divided into fine bins. In each m(K+π-) bin, the hypothesis that the three-dimensional angular distribution can be described by structures induced only by K* resonances is examined, making minimal assumptions about the K+π- system. The data reject the K*-only hypothesis with a large significance, implying the observation of exotic contributions in a model-independent fashion. Inspection of the m(J/ψπ-) vs m(K+π-) plane suggests structures near m(J/ψπ-)=4200 and 4600 MeV

Study of Υ\Upsilon production in ppPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

International audienceThe production of ϒ(nS) mesons (n = 1, 2, 3) in pPb and Pbp collisions at a centre-of-mass energy per nucleon pair $\sqrt{s_{\mathrm{NN}}}=8.16$ TeV is measured by the LHCb experiment, using a data sample corresponding to an integrated luminosity of 31.8 nb$^{−1}$. The ϒ(nS) mesons are reconstructed through their decays into two opposite-sign muons. The measurements comprise the differential production cross-sections of the ϒ(1S) and ϒ(2S) states, their forward-to-backward ratios and nuclear modification factors. The measurements are performed as a function of the transverse momentum p$_{T}$ and rapidity in the nucleon-nucleon centre-of-mass frame y$^{*}$ of the ϒ(nS) states, in the kinematic range p$_{T}$ < 25 GeV/c and 1.5 < y$^{*}$ < 4.0 (−5.0 < y$^{*}$ < −2.5) for pPb (Pbp) collisions. In addition, production cross-sections for ϒ(3S) are measured integrated over phase space and the production ratios between all three ϒ(nS) states are determined. Suppression for bottomonium in proton-lead collisions is observed, which is particularly visible in the ratios. The results are compared to theoretical models

Observation of Several Sources of CPCP Violation in B+→π+π+π−B^+ \to \pi^+ \pi^+ \pi^- Decays

International audienceObservations are reported of different sources of CP violation from an amplitude analysis of B+→π+π+π- decays, based on a data sample corresponding to an integrated luminosity of 3  fb-1 of pp collisions recorded with the LHCb detector. A large CP asymmetry is observed in the decay amplitude involving the tensor f2(1270) resonance, and in addition significant CP violation is found in the π+π-S wave at low invariant mass. The presence of CP violation related to interference between the π+π-S wave and the P wave B+→ρ(770)0π+ amplitude is also established; this causes large local asymmetries but cancels when integrated over the phase space of the decay. The results provide both qualitative and quantitative new insights into CP -violation effects in hadronic B decays

Measurement of Antiproton Production in pHe{\rm p He} Collisions at sNN=110\sqrt{s_{NN}}=110 GeV

International audienceThe cross section for prompt antiproton production in collisions of protons with an energy of 6.5 TeV incident on helium nuclei at rest is measured with the LHCb experiment from a data set corresponding to an integrated luminosity of 0.5  nb-1. The target is provided by injecting helium gas into the LHC beam line at the LHCb interaction point. The reported results, covering antiproton momenta between 12 and 110  GeV/c, represent the first direct determination of the antiproton production cross section in p-He collisions, and impact the interpretation of recent results on antiproton cosmic rays from space-borne experiments

Search for the lepton-flavour violating decays B0→K∗0μ±e∓B^0 \to K^{*0} \mu^\pm e^\mp and Bs0→ϕμ±e∓B_s^0 \to \phi \mu^\pm e^\mp

A search for the lepton-flavour violating decays $B^0 \to K^{*0} \mu^\pm e^\mp$ and $B_s^0 \to \phi \mu^\pm e^\mp$ is presented, using proton-proton collision data collected by the LHCb detector at the LHC, corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$. No significant signals are observed and upper limits of \begin{align} {\cal B}( B^0 \to K^{*0} \mu^+ e^- ) &< \phantom{1}5.7\times 10^{-9}~(6.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^- e^+ ) &< \phantom{1}6.8\times 10^{-9}~(7.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^\pm e^\mp ) &< 10.1\times 10^{-9}~(11.7\times 10^{-9}),\newline {\cal B}( B_s^0 \to \phi \mu^\pm e^\mp ) &< 16.0\times 10^{-9}~(19.8\times 10^{-9}) \end{align} are set at $90\%~(95\%)$ confidence level. These results constitute the world's most stringent limits to date, with the limit on the decay $B_s^0 \to \phi \mu^\pm e^\mp$ the first being set. In addition, limits are reported for scalar and left-handed lepton-flavour violating New Physics scenarios.A search for the lepton-flavour violating decays B$^{0}$ → K$^{*0}$μ$^{±}$e$^{∓}$ and ${B}_s^0$→ ϕμ$^{±}$e$^{∓}$ is presented, using proton-proton collision data collected by the LHCb detector at the LHC, corresponding to an integrated luminosity of 9 fb$^{−1}$. No significant signals are observed and upper limits of${\displaystyle \begin{array}{c}\mathcal{B}\left({B}^0\to {K}^{\ast 0}{\mu}^{+}{e}^{-}\right)<5.7\times {10}^{-9}\left(6.9\times {10}^{-9}\right),\\ {}\mathcal{B}\left({B}^0\to {K}^{\ast 0}{\mu}^{-}{e}^{+}\right)<6.8\times {10}^{-9}\left(7.9\times {10}^{-9}\right),\\ {}\mathcal{B}\left({B}^0\to {K}^{\ast 0}{\mu}^{\pm }{e}^{\mp}\right)<10.1\times {10}^{-9}\left(11.7\times {10}^{-9}\right),\\ {}\mathcal{B}\left({B}_s^0\to \phi {\mu}^{\pm }{e}^{\mp}\right)<16.0\times {10}^{-9}\left(19.8\times {10}^{-9}\right)\end{array}}$are set at 90% (95%) confidence level. These results constitute the world’s most stringent limits to date, with the limit on the decay ${B}_s^0$→ ϕμ$^{±}$e$^{∓}$ the first being set. In addition, limits are reported for scalar and left-handed lepton-flavour violating New Physics scenarios.[graphic not available: see fulltext]A search for the lepton-flavour violating decays $B^0 \to K^{*0} \mu^\pm e^\mp$ and $B_s^0 \to \phi \mu^\pm e^\mp$ is presented, using proton-proton collision data collected by the LHCb detector at the LHC, corresponding to an integrated luminosity of $9\,\text{fb}^{-1}$. No significant signals are observed and upper limits of \begin{align} {\cal B}( B^0 \to K^{*0} \mu^+ e^- ) &< \phantom{1}5.7\times 10^{-9}~(6.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^- e^+ ) &< \phantom{1}6.8\times 10^{-9}~(7.9\times 10^{-9}),\newline {\cal B}( B^0 \to K^{*0} \mu^\pm e^\mp ) &< 10.1\times 10^{-9}~(11.7\times 10^{-9}),\newline {\cal B}( B_s^0 \to \phi \mu^\pm e^\mp ) &< 16.0\times 10^{-9}~(19.8\times 10^{-9}) \end{align} are set at $90\%~(95\%)$ confidence level. These results constitute the world's most stringent limits to date, with the limit on the decay $B_s^0 \to \phi \mu^\pm e^\mp$ the first being set. In addition, limits are reported for scalar and left-handed lepton-flavour violating New Physics scenarios

Evidence for an ηc(1S)π−\eta _c(1S) \pi ^- resonance in B0→ηc(1S)K+π−B^0 \rightarrow \eta _c(1S) K^+\pi ^- decays

International audienceA Dalitz plot analysis of ${{B} ^0} \!\rightarrow \eta _c(1S) {{K} ^+} {{\pi } ^-}$ decays is performed using data samples of pp collisions collected with the $\text{ LHCb }$ detector at centre-of-mass energies of ${\sqrt{s}} =7,~8$ and $13{\,\mathrm {Te}\mathrm {V}}$ , corresponding to a total integrated luminosity of $4.7 \,\text{ fb }^{-1}$ . A satisfactory description of the data is obtained when including a contribution representing an exotic $\eta _c(1S) \pi ^-$ resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are $4096 \pm 20~^{+18-22} \,\mathrm {Me}\mathrm {V}$ and $152 \pm 58~^{+60-35} \,\mathrm {Me}\mathrm {V}$ , respectively. The spin-parity assignments $J^P=0^+$ and $J^{P}=1^-$ are both consistent with the data. In addition, the first measurement of the ${{B} ^0} \!\rightarrow \eta _c(1S) {{K} ^+} {{\pi } ^-}$ branching fraction is performed and gives $\begin{aligned} \displaystyle \mathcal {B}({{B} ^0} \!\rightarrow \eta _c(1S) {{K} ^+} {{\pi } ^-} ) = (5.73 \pm 0.24 \pm 0.13 \pm 0.66) \times 10^{-4}, \end{aligned}$ where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions

Observation of Two Resonances in the Λb0π±\Lambda_b^0 \pi^\pm Systems and Precise Measurement of Σb±\Sigma_b^\pm and Σb∗±\Sigma_b^{*\pm} properties

International audienceThe first observation of two structures consistent with resonances in the final states Λb0π- and Λb0π+ is reported using samples of pp collision data collected by the LHCb experiment at s=7 and 8 TeV, corresponding to an integrated luminosity of 3  fb-1. The ground states Σb± and Σb*± are also confirmed and their masses and widths are precisely measured