Pancreatic transplant surgery and stem cell therapy: Finding the balance between therapeutic advances and ethical principles

The latest achievements in the field of pancreas transplantation and stem cell therapy require an effort by the scientific community to clarify the ethical implications of pioneering treatments, often characterized by high complexity from a surgical point of view, due to transplantation of multiple organs at the same time or at different times, and from an immunological point of view for stem cell therapy. The fundamental value in the field of organ transplants is, of course, a solidarity principle, namely that of protecting the health and life of people for whom transplantation is a condition of functional recovery, or even of survival. The nature of this value is that of a concept to which the legal discipline of transplants entrusts its own ethical dignity and for which it has ensured a constitutional recognition in different systems. The general principle of respect for human life, both of the donor and of the recipient, evokes the need not to put oneself and one's neighbor in dangerous conditions. The present ethical reflection aims to find a balance between the latest therapeutic advances and several concepts including the idea of the person, the respect due to the dead, the voluntary nature of the donation and the consent to the same, the gratuitousness of the donation, the scientific progress and the development of surgical techniques, and the policies of health promotion

Impact of CT Scan Phenotypes in Clinical Manifestations, Management and Outcomes of Hospitalised Patients with COVID-19

COVID-19 is such a heterogeneous disease that a one-size-fits-all approach is not recommended, so the management of patients has been based on their clinical and laboratory characteristics. We therefore investigated possible homogeneous groups presenting similar features of lung involvement based on chest CT and laboratory results. We designed a study to identify a possible correlation between CT scan phenotypes, laboratory exams, and clinical outcomes. We retrospectively analysed 120 adult patients with COVID-19 5who underwent chest CT scan during hospitalisation, between March and December 2020 at our COVID-19 Hospital in two different wards: Respiratory Intensive Care Unit (RICU) and Intensive Care Unit (ICU). The analysis of CT scans resulted in the identification of three radiological phenotypes by two blinded pulmonologists (Cohen's κ = 0.9 for Phenotype 1, 0.9 for Phenotype 2 and 0.89 for Phenotype 3), in accordance with what previously described by Robba et al. “Phenotype 1” (PH1) is characterised by modest interstitial oedema with presentation on chest CT of diffuse ground glass opacities (GGO). “Phenotype 2” (PH2) shows predominant consolidation at lung lobes. “Phenotype 3” (PH3) shows a typical CT pattern of moderate-to-severe ARDS, with alveolar oedema. Based on our results, we could hypothesise that phenotype 2 shows a different trend from all the others and would seem to be more related to a coagulopathy, although we cannot exclude the hypothesis that one phenotype evolves from the other. Further studies might focus on the predictive role of D-dimer, and its cut-offs, in delineating the PH2 patients, that could require an early CT scan to avoid excessive pressure support and finally prevent VILI. To further understand the exact basis of the different CT scan phenotype, a longer longitudinal analysis of clinical and laboratory features (e.g., timing of weaning, pressures and FiO2 delivered) in each phenotype and a comparison among them is needed

LIN7 regulates the filopodia and neurite promoting activity of IRSp53

The insulin receptor substrate protein of 53\u2005kDa (IRSp53) is critically involved in the formation of filopodia and neurites through mechanisms that have only in part been clarified. Here, we investigated the role of the small scaffold protein LIN7, an interactor of IRSp53. We found that formation of actin-filled protrusions in neuronal NSC34 cells and neurites in neuroblastoma N2A depends on motifs mediating the LIN7:IRSp53 association, as both the coexpression of LIN7 with IRSp53 or the expression of the L27-IRSp53 chimera (a fusion protein between IRSp53 and the LIN7L27 domain for plasma membrane protein complexes association) prevented actin-deficient protrusions induced by overexpressed IRSp53, and enhanced the formation of actin-filled protrusions. The regulatory role of LIN7 in IRSp53-mediated extension of filopodia was demonstrated by live-cell imaging experiments in neuronal N2A cells. Moreover, LIN7 silencing prevented the extension of filopodia and neurites, induced by ectopic expression of IRSp53 or serum starvation, respectively in undifferentiated and differentiated N2A cells. The expression of full length IRSp53 or the LIN7\u394PDZ mutant lacking the domain for association with IRSp53 was unable to restore neuritogenesis in LIN7 silenced cells. Conversely, defective neuritogenesis could be rescued by the expression of RNAi-resistant full length LIN7 or chimeric L27-IRSp53. Finally, LIN7 silencing prevented the recruitment of IRSp53 in Triton X-100 insoluble complexes, otherwise occurring in differentiated cells. Collectively these data indicate that LIN7 is a novel regulator of IRSp53, and that their association is required to promote the formation of actin-dependent filopodia and neurites

Interim [18F] Fluorodeoxyglucose Positron Emission Tomography (Pet) for Early Metabolic Assessment of Response to Peb Chemotherapy for Metastatic Seminoma: Preliminary Findings

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PON1 polymorphisms can predict generalized anxiety and depressed mood in patients with multiple chemical sensitivity

Background: Multiple chemical sensitivity (MCS) is a chronic condition with somatic, cognitive and affective symptoms that follow contact with chemical agents at usually non toxic concentrations. We aimed to assess the role of genetic polymorphisms involved in oxidative stress on anxiety and depression in MCS. Materials & methods: Our study investigated the CAT rs1001179, MPO rs2333227, PON1 rs662 and PON1 rs705379 polymorphisms in MCS. Results: The AG genotype of the PON1 rs662 and the TT and CT genotypes of the PON1 rs705379 were involved in anxiety and depression. Discussion: These results are in line with existing evidence of PON1 involvement in MCS and suggest a further role of this gene in the exhibition of anxiety and depression in this disease

Correlations between flow and transverse momentum in Xe+Xe and Pb+Pb collisions at the LHC with the ATLAS detector: A probe of the heavy-ion initial state and nuclear deformation

The correlations between flow harmonics v_n for n=2, 3, and 4 and mean transverse momentum [pT] in 129Xe+129Xe and 208Pb+208Pb collisions at sqrt(s)=5.44 and 5.02 TeV, respectively, are measured using charged particles with the ATLAS detector. The correlations are potentially sensitive to the shape and size of the initial geometry, nuclear deformation, and initial momentum anisotropy. The effects from nonflow and centrality fluctuations are minimized, respectively, via a subevent cumulant method and an event-activity selection based on particle production at very forward rapidity. The v_n−[pT] correlations show strong dependencies on centrality, harmonic number n, pT, and pseudorapidity range. Current models qualitatively describe the overall centrality- and system-dependent trends but fail to quantitatively reproduce all features of the data. In central collisions, where models generally show good agreement, the v_2−[pT] correlations are sensitive to the triaxiality of the quadruple deformation. Comparison of the model with the Pb+Pb and Xe+Xe data confirms that the 129Xe nucleus is a highly deformed triaxial ellipsoid that has neither a prolate nor oblate shape. This provides strong evidence for a triaxial deformation of the 129Xe nucleus from high-energy heavy-ion collisions

Measurements of the suppression and correlations of dijets in Pb+Pb collisions at sqrt(s_NN)=5.02 TeV

Studies of the correlations of the two highest transverse momentum (leading) jets in individual Pb+Pb collision events can provide information about the mechanism of jet quenching by the hot and dense matter created in such collisions. In Pb+Pb and pp collisions at sqrt(s_NN)=5.02 TeV, measurements of the leading dijet transverse momentum (pT) correlations are presented. Additionally, measurements in Pb+Pb collisions of the dijet pair nuclear modification factors projected along leading and subleading jet pT are made. The measurements are performed using the ATLAS detector at the LHC with 260 pb^{−1} of pp data collected in 2017 and 2.2 nb^{−1} of Pb+Pb data collected in 2015 and 2018. An unfolding procedure is applied to the two-dimensional leading and subleading jet pT distributions to account for experimental effects in the measurement of both jets. Results are provided for dijets with leading jet pT greater than 100 GeV. Measurements of the dijet-yield-normalized xJ distributions in Pb+Pb collisions show an increased fraction of imbalanced jets compared to pp collisions; these measurements are in agreement with previous measurements of the same quantity at 2.76 TeV in the overlapping kinematic range. Measurements of the absolutely normalized dijet rate in Pb+Pb and pp collisions are also presented, and show that balanced dijets are significantly more suppressed than imbalanced dijets in Pb+Pb collisions. It is observed in the measurements of the pair nuclear modification factors that the subleading jets are significantly suppressed relative to leading jets with pT between 100 and 316 GeV for all centralities in Pb+Pb collisions

Measurement of the nuclear modification factor of b-jets in 5.02 TeV Pb+Pb collisions with the ATLAS detector

This paper presents a measurement of b-jet production in Pb+Pb and pp collisions at sqrt(s_NN)=5.02 TeV with the ATLAS detector at the LHC. The measurement uses 260 pb^{−1} of pp collisions collected in 2017 and 1.4 nb^{−1} of Pb+Pb collisions collected in 2018. In both collision systems, jets are reconstructed via the anti-kt algorithm. The b-jets are identified from a sample of jets containing muons from the semileptonic decay of b-quarks using template fits of the muon momentum relative to the jet axis. In pp collisions, b-jets are reconstructed for radius parameters R=0.2 and R=0.4, and only R=0.2 jets are used in Pb+Pb collisions. For comparison, inclusive R=0.2 jets are also measured using 1.7 nb^{−1} of Pb+Pb collisions collected in 2018 and the same pp collision data as the b-jet measurement. The nuclear modification factor, R_{AA}, is calculated for both b-jets and inclusive jets with R=0.2 over the transverse momentum range of 80-290 GeV. The nuclear modification factor for b-jets decreases from peripheral to central collisions. The ratio of the b-jet R_{AA} to inclusive jet R_{AA} is also presented and suggests that the R_{AA} for b-jets is larger than that for inclusive jets in central Pb+Pb collisions. The measurements are compared with theoretical calculations and suggest a role for mass and colour-charge effects in partonic energy loss in heavy-ion collisions

Production of Υ(nS) mesons in Pb+Pb and pp collisions at 5.02 TeV

A measurement of the production of vector bottomonium states, Υ(1S), Y(2S), and Υ(3S), in Pb+Pb and pp collisions at a center-of-mass energy per nucleon pair of 5.02 TeV is presented. The data correspond to integrated luminosities of 1.38 nb^{−1} of Pb+Pb data collected in 2018, 0.44 nb^{−1} of Pb+Pb data collected in 2015, and 0.26 fb^{−1} of pp data collected in 2017 by the ATLAS detector at the Large Hadron Collider. The measurements are performed in the dimuon decay channel for transverse momentum p^{μμ}_T<30 GeV, absolute rapidity |y^{μμ}|<1.5, and Pb+Pb event centrality 0–80%. The production rates of the three bottomonium states in Pb+Pb collisions are compared with those in pp collisions to extract the nuclear modification factors as functions of event centrality, p^{μμ}_T, and |y^{μμ}|. In addition, the suppression of the excited states relative to the ground state is studied. The results are compared with theoretical model calculations