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Receiver operating characteristic curves were generated to determine the optimal cutoff TNRs. RESULTS The optimal TNRs for differentiating complete response and unconfirmed complete response from tumor mass were 1.83 (area under the curve, 0.951) and 1.80 (area under the curve, 0.932), respectively. The corresponding sensitivity and specificity values for the diagnosis of tumor mass were 82.4 and 100%, respectively, in the complete response group and 85.3 and 85%, respectively, in the unconfirmed complete response group. CONCLUSIONS A TNR of ≥1.80 can aid in the detection of active PCNSL using 11C-Met PET. Thus, 11C-Met-PET may be a useful tool for accurate evaluation of the treatment efficacy in PCNSL. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail journals.permission@oup.com.Some mutations affecting Dynamin 2 (DNM2) can cause dominantly-inherited Charcot-Marie-Tooth (CMT) neuropathy. Here, we describe the analysis of mice carrying the DNM2 K562E mutation which has been associated with dominant-intermediate CMT type B (CMTDIB). Contrary to our expectations, heterozygous DNM2 K562E mutant mice did not develop definitive signs of an axonal or demyelinating neuropathy. Rather, we found a primary myopathy-like phenotype in these mice. A likely interpretation of these results is that the lack of a neuropathy in this mouse model has allowed the unmasking of a primary myopathy due to the DNM2 K562E mutation which might be overshadowed by the neuropathy in humans. Consequently, we hypothesize that a primary myopathy may also contribute to the disease mechanism in some CMTDIB patients. We propose that these findings should be considered in the evaluation of patients, the determination of the underlying disease processes, and the development of tailored potential treatment strategies. © The Author(s) 2020. Published by Oxford University Press.Gestational diabetes mellitus (GDM) is a global health issue, whereby pregnant women are afflicted with carbohydrate intolerance with first onset during pregnancy. GDM is characterized by maternal peripheral insulin resistance, thought to be driven by low-grade maternal inflammation. Nobiletin, a polymethoxylated flavonoid, possesses potent glucose-sensitizing and anti-inflammatory properties; however, its effects in GDM have not been assessed. The present study aimed to determine the effects of nobiletin on glucose metabolism and inflammation associated with GDM in both in vitro human tissues and an in vivo animal model of GDM. In vitro, treatment with nobiletin significantly improved TNF-impaired glucose uptake in human skeletal muscle, and suppressed mRNA expression and protein secretion of pro-inflammatory cytokines and chemokines in human placenta and visceral adipose tissue (VAT). Mechanistically, nobiletin significantly inhibited Akt and Erk activation in placenta, and NF-κB activation in VAT. In vivo, GDM mice treated with 50 mg/kg nobiletin daily via oral gavage from gestational day (gd) 1-17 or via i.p. injections from gd 10-17 significantly improved glucose tolerance. Pregnant GDM mice treated with nobiletin from either gd 1-17 or gd 10-17 exhibited significantly suppressed mRNA expression of pro-inflammatory cytokines and chemokines in placenta, VAT and subcutaneous adipose tissue (SAT). Using a quantitative mass spectrometry approach, we identified differentially abundant proteins associated with the effect of nobiletin in vivo. Together, these studies demonstrate that nobiletin improves glucose metabolism and reduces inflammation associated with GDM and may be a novel therapeutic for the prevention of GDM. © 2020 The Author(s).Small extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were upregulated and 301 were downregulated (p less then 0.05), and they were mainly implicated in inflammation-related pathways. In vitroincubation of hypoxic sEVs with endothelial cells, significantly increased (p less then 0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared to control (i.e., cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (p less then 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. Cell Cycle inhibitor We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia. Copyright 2020 The Author(s).BACKGROUND For patients at risk for multidrug-resistant organisms, IDSA/ATS guidelines recommend empiric therapy against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas. Following negative cultures, the guidelines recommend antimicrobial de-escalation. We assessed antibiotic de-escalation practices across hospitals and their associations with outcomes in hospitalized pneumonia patients with negative cultures. METHODS We included adults admitted with pneumonia in 2010-2015 to 164 US hospitals if they had negative blood and/or respiratory cultures and received both anti-MRSA and antipseudomonal agents other than quinolones. De-escalation was defined as stopping both empiric drugs on day 4 while continuing another antibiotic. Patients were propensity-adjusted for de-escalation and compared on in-hospital 14-day mortality, late deterioration (ICU transfer), length-of-stay (LOS) and costs. We also compared adjusted outcomes across hospital de-escalation rate quartiles. RESULTS Of 14,170 patients, 1924 (13%) had both initial empiric drugs stopped by hospital day 4.