Platelet activation is associated with myocardial infarction in patients with pneumonia

BACKGROUND: Troponins may be elevated in patients with pneumonia, but associations with myocardial infarction (MI) and with platelet activation are still undefined.OBJECTIVES: The aim of this study was to investigate the relationship between troponin elevation and in vivo markers of platelet activation in the early phase of hospitalization of patients affected by community-acquired pneumonia.METHODS: A total of 278 consecutive patients hospitalized for community-acquired pneumonia, who were followed up until discharge, were included. At admission, platelet activation markers such as plasma soluble P-selectin, soluble CD40 ligand, and serum thromboxane B2 (TxB2) were measured. Serum high-sensitivity cardiac troponin T levels and electrocardiograms were obtained every 12 and 24 h, respectively.RESULTS: Among 144 patients with elevated high-sensitivity cardiac troponin T, 31 had signs of MI and 113 did not. Baseline plasma levels of soluble P-selectin and soluble CD40 ligand and serum TxB2 were significantly higher in patients who developed signs of MI. Logistic regression analysis showed plasma soluble CD40 ligand (p < 0.001) and soluble P-selectin (p < 0.001), serum TxB2 (p = 0.030), mean platelet volume (p = 0.037), Pneumonia Severity Index score (p = 0.030), and ejection fraction (p = 0.001) to be independent predictors of MI. There were no significant differences in MI rate between the 123 patients (45%) taking aspirin (100 mg/day) and those who were not aspirin treated (12% vs. 10%; p = 0.649). Aspirin-treated patients with MIs had higher serum TxB2 compared with those without MIs (p = 0.005).CONCLUSIONS: MI is an early complication of pneumonia and is associated with in vivo platelet activation and serum TxB2 overproduction; aspirin 100 mg/day seems insufficient to inhibit thromboxane biosynthesis. (MACCE in Hospitalized Patients With Community-acquired Pneumonia; NCT01773863)

Pancreas tissue slices from organ donors enable in situ analysis of type 1 diabetes pathogenesis.

In type 1 diabetes (T1D), autoimmune destruction of pancreatic beta cells leads to insulin deficiency and loss of glycemic control. However, knowledge about human pancreas pathophysiology in T1D remains incomplete. To address this limitation, we established a pancreas tissue slice platform of donor organs with and without diabetes, facilitating the first live cell studies of human pancreas in T1D pathogenesis to our knowledge. We show that pancreas tissue slices from organ donors allow thorough assessment of processes critical for disease development, including insulin secretion, beta cell physiology, endocrine cell morphology, and immune infiltration within the same donor organ. Using this approach, we compared detailed pathophysiological profiles for 4 pancreata from donors with T1D with 19 nondiabetic control donors. We demonstrate that cell loss, beta cell dysfunction, alterations of beta cell physiology, and islet infiltration contributed differently to individual cases of T1D, allowing insight into pathophysiology and heterogeneity of T1D pathogenesis. Thus, our study demonstrates that organ donor pancreas tissue slices represent a promising and potentially novel approach in the search for successful prevention and reversal strategies of T1D

The ATLAS experiment at the CERN Large Hadron Collider: a description of the detector configuration for Run 3

The ATLAS detector is installed in its experimental cavern at Point 1 of the CERN Large Hadron Collider. During Run 2 of the LHC, a luminosity of ℒ = 2 × 1034 cm-2 s-1 was routinely achieved at the start of fills, twice the design luminosity. For Run 3, accelerator improvements, notably luminosity levelling, allow sustained running at an instantaneous luminosity of ℒ = 2 × 1034 cm-2 s-1, with an average of up to 60 interactions per bunch crossing. The ATLAS detector has been upgraded to recover Run 1 single-lepton trigger thresholds while operating comfortably under Run 3 sustained pileup conditions. A fourth pixel layer 3.3 cm from the beam axis was added before Run 2 to improve vertex reconstruction and b-tagging performance. New Liquid Argon Calorimeter digital trigger electronics, with corresponding upgrades to the Trigger and Data Acquisition system, take advantage of a factor of 10 finer granularity to improve triggering on electrons, photons, taus, and hadronic signatures through increased pileup rejection. The inner muon endcap wheels were replaced by New Small Wheels with Micromegas and small-strip Thin Gap Chamber detectors, providing both precision tracking and Level-1 Muon trigger functionality. Trigger coverage of the inner barrel muon layer near one endcap region was augmented with modules integrating new thin-gap resistive plate chambers and smaller-diameter drift-tube chambers. Tile Calorimeter scintillation counters were added to improve electron energy resolution and background rejection. Upgrades to Minimum Bias Trigger Scintillators and Forward Detectors improve luminosity monitoring and enable total proton-proton cross section, diffractive physics, and heavy ion measurements. These upgrades are all compatible with operation in the much harsher environment anticipated after the High-Luminosity upgrade of the LHC and are the first steps towards preparing ATLAS for the High-Luminosity upgrade of the LHC. This paper describes the Run 3 configuration of the ATLAS detector