Alterations of hemostatic parameters in the early development of allogeneic hematopoietic stem cell transplantation-related complications

Thrombotic events are common and potentially fatal complications in patients receiving hematopoietic stem cell transplantation (HSCT). Early diagnosis is crucial but remains controversial. In this study, we investigated the early alterations of hemostatic parameters in allogeneic HSCT recipients and determined their potential diagnostic values in transplantation-related thrombotic complications and other post-HSCT events. Results from 107 patients with allogeneic HSCT showed higher levels of plasma plasminogen activator inhibitor-1 (PAI-1), fibrinogen, and tissue-plasminogen activator (t-PA) and a lower level of plasma protein C after transplantation. No change was found for prothrombin time, antithrombin III, d-dimer, and activated partial thromboplastin time following HSCT. Transplantation-related complications (TRCs) in HSCT patients were defined as thrombotic (n = 8), acute graft-versus-host disease (aGVHD, n = 45), and infectious (n = 38). All patients with TRCs, especially the patients with thrombotic complications, presented significant increases in the mean and maximum levels of PAI-1 during the observation period. Similarly, a high maximum t-PA level was found in the thrombotic group. In contrast, apparent lower levels of mean and minimum protein C were observed in the TRC patients, especially in the aGVHD group. Therefore, the hemostatic imbalance in the early phase of HSCT, reflecting prothrombotic state and endothelial injury due to the conditioning therapy or TRCs, might be useful in the differential diagnosis of the thrombotic complication from other TRCs

Transcutaneous spinal stimulation alters cortical and subcortical activation patterns during mimicked-standing: A proof-of-concept fMRI study

Transcutaneous spinal stimulation (TSS) is a non-invasive neuromodulation technique that has been used to facilitate the performance of voluntary motor functions such as trunk control and self-assisted standing in individuals with spinal cord injury. Although it is hypothesized that TSS amplifies signals from supraspinal motor control networks, the effect of TSS on supraspinal activation patterns is presently unknown. The purpose of this study was to investigate TSS-induced activity in supraspinal sensorimotor regions during a lower-limb motor task. Functional magnetic resonance imaging (fMRI) was used to assess changes in neural activation patterns as eleven participants performed mimicked-standing movements in the scanner. Movements were performed without stimulation, as well as in the presence of (1) TSS, (2) stimulation applied to the back muscle, (3) paresthesia stimulation, and (4) neuromuscular electrical stimulation. TSS was associated with greater activation in subcortical and cortical sensorimotor regions involved in relay and processing of movement-related somatosensory information (e.g., thalamus, caudate, pallidum, putamen), as compared to the other stimulation paradigms. TSS also resulted in deactivation in both nucleus accumbens and posterior parietal cortex, suggesting a shift toward somatosensory feedback-based mechanisms and more reflexive motor control. Together, these findings demonstrate that spinal stimulation can alter the activity within supraspinal sensorimotor networks and promote the use of somatosensory feedback, thus providing a plausible neural mechanism for the stimulation-induced improvements of sensorimotor function observed in participants with neurological injuries and disorders

The Management of Autoimmune Hepatitis Patients with Decompensated Cirrhosis: Real-World Experience and a Comprehensive Review.

There is a paucity of information related to the usefulness of corticosteroid therapy in autoimmune hepatitis (AIH) with decompensated cirrhosis. In this study, we sought to determine the therapeutic effect of corticosteroids in this special group of AIH patients. Eighty-two AIH patients with decompensated cirrhosis were included through a retrospective analysis from January 2009 to September 2015. Sixty-four patients were treated with corticosteroids while 18 patients did not receive any corticosteroids. Clinical, laboratory, and histological characteristics and outcomes were analyzed comparing corticosteroid-treated and untreated groups. Patients that did not receive corticosteroids were older than corticosteroid-treated patients and had a worse survival. In corticosteroid-treated group, 40 of 64 patients reverted to compensated state and 15 patients remained decompensated, while 9 patients experienced liver-related death or transplantation. Patients who reverted to compensated state had significantly greater ALT, AST, GGT, white blood cell count, and platelet levels at presentation. Changes (Δ) in total bilirubin (TBIL) and MELD scores at day 7 after starting corticosteroid therapy revealed favorable predictive effects of treatment outcomes. Survival was significantly greater in patients with a ΔTBIL <-0.196 mg/dL (p = 0.001) 7 days after treatment. Infection was the most common cause of death or transplantation in the patients with treatment failure. Although it cannot be determined whether the results were due to the therapy or underlying patient characteristics, survival was greater in the corticosteroid-treated group with the benefit being greatest in patients with the greatest decrease in TBIL at day 7 after starting corticosteroid therapy

Conserved function of the lysine-based KXD/E motif in Golgi retention for endomembrane proteins among different organisms

We recently identified a new COPI-interacting KXD/E motif in the C-terminal cytosolic tail (CT) of Arabidopsis endomembrane protein 12 (AtEMP12) as being a crucial Golgi retention mechanism for AtEMP12. This KXD/E motif is conserved in CTs of all EMPs found in plants, yeast, and humans and is also present in hundreds of other membrane proteins. Here, by cloning selective EMP isoforms from plants, yeast, and mammals, we study the localizations of EMPs in different expression systems, since there are contradictory reports on the localizations of EMPs. We show that the N-terminal and C-terminal GFP-tagged EMP fusions are localized to Golgi and post-Golgi compartments, respectively, in plant, yeast, and mammalian cells. In vitro pull-down assay further proves the interaction of the KXD/E motif with COPI coatomer in yeast. COPI loss of function in yeast and plants causes mislocalization of EMPs or KXD/E motif–containing proteins to vacuole. Ultrastructural studies further show that RNA interference (RNAi) knockdown of coatomer expression in transgenic Arabidopsis plants causes severe morphological changes in the Golgi. Taken together, our results demonstrate that N-terminal GFP fusions reflect the real localization of EMPs, and KXD/E is a conserved motif in COPI interaction and Golgi retention in eukaryotes