A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

PURPOSE: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles. METHODS: We performed a prospective observational 12-month multicenter study in France via the CEREDIH network of regional PID reference centers from November 2010 to October 2011. All patients with PIDs requiring emergency hospital admission were included. RESULTS: A total of 200 admissions concerned 137 patients (73 adults and 64 children, 53% of whom had antibody deficiencies). Thirty admissions were reported for 16 hematopoietic stem cell transplantation recipients. When considering the 170 admissions of non-transplant patients, 149 (85%) were related to acute infections (respiratory tract infections and gastrointestinal tract infections in 72 (36%) and 34 (17%) of cases, respectively). Seventy-seven percent of the admissions occurred during winter or spring (December to May). The in-hospital mortality rate was 8.8% (12 patients); death was related to a severe infection in 11 cases (8%) and Epstein-Barr virus-induced lymphoma in 1 case. Patients with a central venous catheter (n = 19, 13.9%) were significantly more hospitalized for an infection (94.7%) than for a non-infectious reason (5.3%) (p = 0.04). CONCLUSION: Our data showed that the annual incidence of emergency hospital admission among patients with PID is 3.4%. The leading cause of emergency hospital admission was an acute infection, and having a central venous catheter was associated with a significantly greater risk of admission for an infectious episode

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Dry Weight Production and Nitrogen Efficiency Traits in Kentucky Bluegrass Cultivars in Nutrient Solution and Soil

Because of the importance of such factors as appearance and vigor in turf management, genetic selection of Kentucky bluegrass (Poa pratensis L.) is often conducted at high levels of N application. This process can mask potential differences between genotypes in N efficiency, especially under low N levels. The case is also made that because soil is the medium in which plant selections ultimately must perform, cultivar screening for N efficiency in solution culture should relate to results in soil. This study was conducted to evaluate N-utilization efficiency (NUE – mg plant dry matter mg-1 plant N) in six bluegrass cultivars at low (0.2, 0.7 mM NO3-N) and high (3.5 mM NO3-N) levels of N supply in nutrient solution culture (nutriculture) and soil. With high N supply, total plant N accumulation and N-root uptake efficiency (NRE-mg plant N g-1 root dry matter) increased in each cultivar, while NUE and shoot efficiency ratio (SER–mg shoot dry matter mg-1 shoot N) decreased, with the magnitude and relative response dependent on genotype and medium. As a group, as well as individually, cultivars Asset, Dawn, and Trenton were higher yielding, more responsive to increasing solution N concentration, and more efficient (NUE) at low levels of N supply than cultivars Limousine, Barzan, or Midnight. Under low N supply, NUE in nutriculture ranged from 26.2 (g plant dry weight mg-1 N) in Limousine to 40.1 in Asset, and in soil from 63.6 in Midnight to 77.4 in Asset. Differences in NUE among cultivars were more associated with shoot efficiency than with root absorption efficiency. Despite noticeably higher NUE in soil than in nutriculture, and significant effects of N fertility, genotypic differences in the various N efficiency traits in solution culture were also apparent in soil. The results suggest that NUE in Kentucky bluegrass can be enhanced by cultivar selection under low-N conditions. While the similarities of the actual N conditions between nutriculture and soil remain in question, it appears that solution culture can be used as an effective surrogate for characterizing NUE in divergent types of bluegrass cultivars

Nitrogen Utilization Efficiency of Creeping Bentgrass Genotypes

A greenhouse study was conducted in a hydroponic system to determine the nitrogen (N) utilization efficiency (NUE) of 14 creeping bentgrass cultivars. There were significant differences among cultivars in plant tissue dry weight, tissue N content, root absorption efficiency (RAE), and NUE. Considering all plant tissue (whole plant), \u27Penncross\u27 accumulated the highest N accompanied with the highest whole plant dry weight (WPDW), while \u27Allure\u27 accumulated the lowest total Nand WPDW than all the other cultivars. The proportion of WPDW and total N partitioned to shoots was higher than partitioned to roots in each cultivar. On a whole plant basis, \u27Regent\u27 had the highest NUE while \u27Allure\u27 had the lowest NUE. N absorption efficiency values were comparatively higher in \u27Allure\u27 than any of the other cultivars, while \u27Forbes\u27 had the lowest RAE. The RAE value of the cultivars was not a response to the NUE indicating that differences in RAE was not a critical factor involved in genotypic differences in NUE. Differences in NUE among most cultivars were correlated to plant dry weight in a second experiment. Solution systems have the potential for an effective means of screening the NUE of creeping bentgrass cultivars

Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids

15 p.-6 fig.Mitophagy is a critical cellular process that selectively targets damaged mitochondria for autophagosomal degradation both under baseline conditions and in response to stress preventing oxidative damage and cell death. Recent studies have linked alterations in mitochondria function and reduced autophagy with the development of age-related pathologies. However, the significance of mitochondrial autophagy in vessel wall in response to atherogenic lipid stressors is not known. In the present study, we investigated the role of mitophagy on human vascular smooth muscle cells (VSMC) apoptosis induced by oxidized low-density lipoproteins (LDL). We reported for the first time that the engulfment of defective mitochondria by autophagosomes occurred in human VSMC in response to oxidized LDL. The molecular mechanism mediating mitophagy in human VSMC involved dynamin-related protein 1 (Drp1)-mediated mitochondrial fission, accumulation of PTEN-induced putative kinase 1 (PINK1) and the recruitment of the E3 ubiquitin ligase Parkin to mitochondria. Likewise, we found increased voltage-dependent anion channel 1 (VDAC1) and mitofusin 2 (Mnf2) mitochondrial proteins ubiquitination and LC3 association to mitochondria. Using flow cytometry in the presence of lysosomal inhibitors, we showed that PINK1 and Parkin silencing impaired mitophagy flux and enhanced oxidized LDL-induced VSMC apoptosis. In addition, overexpression of PINK1 and Parkin were protective by limiting cell death. Moreover, reduced Bax levels found in VSMC-overexpressing Parkin indicated cross talk among mitophagy and mitochondrial apoptotic signalling pathways. Altogether these data demonstrate that mitophagy is a safeguard mechanism against human VSMC apoptosis induced by atherogenic stressors and highlight mitophagy as a potential target to stabilize atherosclerotic plaque.This work was supported by grants from l’Institut National de la Santé et de la Recherche Médicale (INSERM) and Fondation de France [2013-38581 to C.V] and FU2015-64623-R to PB.Peer reviewe