571 research outputs found

    Exogenous Fungal Endophthalmitis: Clues to Aspergillus Aetiology with a Pharmacological Perspective.

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    Exogenous fungal endophthalmitis (EXFE) represents a rare complication after penetrating ocular trauma of previously unresolved keratitis or iatrogenic infections, following intraocular surgery such as cataract surgery. The usual latency period between intraocular inoculation and presentation of symptoms from fungal endophthalmitis is several weeks to months as delayed-onset endophthalmitis. Aspergillus spp., is the most common causative mould pathogen implicated in this ocular infection and early diagnosis and prompt antimicrobial treatment, concomitantly in most cases with expert surgical attention, reduce unfavorable complications and increase the possibility of eye function preservation. Topical, intravitreal and systemic antifungal molecules are the mainstay of a medical approach to the disease and azoles, polyenes and in particular cases echinocandins are the pharmacological classes most commonly used in clinical practice. This review discusses pharmacokinetics and pharmacodynamic of antifungal agents in their principal modes of administration with a focus on their ability to achieve high drug concentration in the vitreous and ocular tissues

    Correctors of mutant CFTR enhance subcortical cAMP-PKA signaling through modulating ezrin phosphorylation and cytoskeleton organization

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    The most common mutation of the cystic fibrosis transmembrane regulator (CFTR) gene, F508del, produces a misfolded protein resulting in its defective trafficking to the cell surface and an impaired chloride secretion. Pharmacological treatments partially rescue F508del CFTR activity either directly by interacting with the mutant protein and/or indirectly by altering the cellular protein homeostasis. Here, we show that the phosphorylation of ezrin together with its binding to phosphatidylinositol-4,5-bisphosphate (PIP2) tethers the F508del CFTR to the actin cytoskeleton, stabilizing it on the apical membrane and rescuing the sub-membrane compartmentalization of cAMP and activated PKA. Both the small molecules trimethylangelicin (TMA) and VX-809, which act as 'correctors' for F508del CFTR by rescuing F508del-CFTR-dependent chloride secretion, also restore the apical expression of phosphorylated ezrin and actin organization and increase cAMP and activated PKA submembrane compartmentalization in both primary and secondary cystic fibrosis airway cells. Latrunculin B treatment or expression of the inactive ezrin mutant T567A reverse the TMA and VX-809-induced effects highlighting the role of corrector-dependent ezrin activation and actin re-organization in creating the conditions to generate a sub-cortical cAMP pool of adequate amplitude to activate the F508del-CFTR-dependent chloride secretion

    Procés d'atenció social de treball social sanitari individual i familiar

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    Treball social; GestióTrabajo social; GestiónSocial work; ManagementDocument que identifica i avalua les necessitats socials i familiars, i el malestar psicosocial derivat d'aquestes que poden dificultar el procés de salut, disminuint la capacitat de maneig del problema de salut, i condicionar la utilització dels serveis sanitaris.Document that identifies and evaluates social and family needs, and the psychosocial discomfort derived from these that can hinder the health process, reduce the ability to manage health problems, and condition the use of health services.Documento que identifica y evalúa las necesidades sociales y familiares, y el malestar psicosocial derivado de estos que pueden dificultar el proceso de salud, disminuir la capacidad de manejo de los problemas de salud, y condicionar la utilización de los servicios sanitarios

    Tm,Ho:Ca(Gd,Lu)AlO4 crystals: Crystal growth, structure refinement and Judd-Ofelt analysis

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    “Mixed” calcium rare-earth aluminate laser host crystals Ca(Gd,Lu)AlO4 (CALGLO) with up to 10.8 at.% Lu codoped with Tm3 + and Ho3 + ions are grown by the Czochralski method along the [001] direction. The segregation of rare-earth ions is studied. The crystal structure is refined by the Rietveld method. Tm,Ho:Ca(Gd, Lu)AlO4 crystallizes in the tetragonal system (sp. gr. I4/mmm) exhibiting a K2NiF4 type structure. The lattice constants are a = 3.6585(6) Å and c = 11.9660(9) Å for a crystal with a composition of CaG-d0.8947Lu0.0551Tm0.0448Ho0.0054AlO4. The stability of Ca(Gd,Lu)AlO4 solid-solutions is discussed. The polarized Raman spectra are measured, revealing a most intense mode at 311 cm 1 and a maximum phonon frequency of ~650 cm 1. The polarized absorption spectra are measured. The transition intensities for the Ho3 + ion are analyzed using the modified Judd-Ofelt theory accounting for configuration interaction

    Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

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    Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

    Study of the BΛc+ΛˉcKB^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

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    The decay BΛc+ΛˉcKB^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} is studied in proton-proton collisions at a center-of-mass energy of s=13\sqrt{s}=13 TeV using data corresponding to an integrated luminosity of 5 fb1\mathrm{fb}^{-1} collected by the LHCb experiment. In the Λc+K\Lambda_{c}^+ K^{-} system, the Ξc(2930)0\Xi_{c}(2930)^{0} state observed at the BaBar and Belle experiments is resolved into two narrower states, Ξc(2923)0\Xi_{c}(2923)^{0} and Ξc(2939)0\Xi_{c}(2939)^{0}, whose masses and widths are measured to be m(Ξc(2923)0)=2924.5±0.4±1.1MeV,m(Ξc(2939)0)=2938.5±0.9±2.3MeV,Γ(Ξc(2923)0)=0004.8±0.9±1.5MeV,Γ(Ξc(2939)0)=0011.0±1.9±7.5MeV, m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV}, where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt Λc+K\Lambda_{c}^{+} K^{-} sample. Evidence of a new Ξc(2880)0\Xi_{c}(2880)^{0} state is found with a local significance of 3.8σ3.8\,\sigma, whose mass and width are measured to be 2881.8±3.1±8.5MeV2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV} and 12.4±5.3±5.8MeV12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}, respectively. In addition, evidence of a new decay mode Ξc(2790)0Λc+K\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-} is found with a significance of 3.7σ3.7\,\sigma. The relative branching fraction of BΛc+ΛˉcKB^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} with respect to the BD+DKB^{-} \to D^{+} D^{-} K^{-} decay is measured to be 2.36±0.11±0.22±0.252.36 \pm 0.11 \pm 0.22 \pm 0.25, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

    Measurement of the ratios of branching fractions R(D)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

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    The ratios of branching fractions R(D)B(BˉDτνˉτ)/B(BˉDμνˉμ)\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu}) and R(D0)B(BD0τνˉτ)/B(BD0μνˉμ)\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu}) are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb1{ }^{-1} of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode τμντνˉμ\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}. The measured values are R(D)=0.281±0.018±0.024\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024 and R(D0)=0.441±0.060±0.066\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is ρ=0.43\rho=-0.43. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

    Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

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    Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a ZZ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 <pT<100< p_{\textrm{T}} < 100 GeV and in the pseudorapidity range 2.5<η<42.5 < \eta < 4. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb1^{-1}. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

    Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

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    Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries
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