Immune Profiling of Peripheral Blood Mononuclear Cells at Pancreas Acute Rejection Episodes in Kidney-Pancreas Transplant Recipients

Profiling of circulating immune cells provides valuable insight to the pathophysiology of acute rejection in organ transplantation. Herein we characterized the peripheral blood mononuclear cells in simultaneous kidney-pancreas transplant recipients. We conducted a retrospective analysis in a biopsy-matched cohort (n = 67) and compared patients with biopsy proven acute rejection (BPAR; 41%) to those without rejection (No-AR). We observed that CD3+ T cells, both CD8+ and CD4+, as well as CD19+ B cells were increased in patients with BPAR, particularly in biopsies performed in the early post-transplant period (<3 months). During this period immune subsets presented a good discriminative ability (CD4+ AUC 0.79; CD8+ AUC 0.80; B cells AUC 0.86; p < 0.05) and outperformed lipase (AUC 0.62; p = 0.12) for the diagnosis of acute rejection. We further evaluated whether this could be explained by differences in frequencies prior to transplantation. Patients presenting with early post-transplant rejection (<3 months) had a significant increase in T-cell frequencies pre-transplant, both CD4+ T cells and CD8+ T cells (p < 0.01), which were associated with a significant inferior rejection-free graft survival. T cell frequencies in peripheral blood correlated with pancreas acute rejection episodes, and variations prior to transplantation were associated with pancreas early acute rejection.Copyright © 2022 Rovira, Ramirez-Bajo, Bañón-Maneus, Hierro-Garcia, Lazo-Rodriguez, Piñeiro, Montagud-Marrahi, Cucchiari, Revuelta, Cuatrecasas, Campistol, Ricart, Diekmann, Garcia-Criado and Ventura-Aguiar

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD