BACKGROUND: Little is known about the clinical impact on cardiovascular stability during intermittent haemodialysis (IHD) for acute kidney injury (AKI) of online monitoring devices that control blood volume (BV) and blood temperature in the intensive care unit (ICU) setting. We compared different dialysis treatment modalities with or without these new systems among critically ill patients requiring IHD.METHODS: In a prospective single-centre three-arm randomized controlled trial, 600 dialysis sessions in 74 consecutive AKI critically ill patients were involved to assess intradialytic hypotension. Standard dialysis therapy with constant ultrafiltration (UF) rate, cool dialysate and high sodium conductivity (Treatment A) was compared to regimens with adjunctive interventions including BV control (Treatment B) and the combination of BV and active blood temperature control (Treatment C). Each dialysis session was randomly assigned to one of the three treatment arms and served as statistical unit.RESULTS: Five hundred and seventy-two dialysis sessions were analysed (188, 190 and 194 in Treatments A, B and C, respectively). Hypotension occurred in 16.6% treatments, with similar rates among the arms. Haemodynamic parameters and dialysis-related complications did not differ between therapies. Based on generalized estimating equation adjusted to dialysate sodium conductivity, higher Sequential Organ Failure Assessment the day of dialysis session, the need for vasopressors and lower systolic blood pressure at the onset of the session were identified as independent predictors of hypotensive episodes, whereas regimens containing the new online monitors were not.CONCLUSIONS: These results suggest that both actively controlled body temperature and UF profiled by online monitoring systems have no significant impact on the incidence of intradialytic hypotension in the ICU setting. Further research is needed before the use of these new sophisticated automatic methods can be applied routinely to the ICU setting.

In this issue of Molecular Cell, Sanvisens et al.(2011) report a new mechanism for regulation of yeast ribonucleotide reductase activity that occurs during iron deprivation.

A 1149 bp genomic fragment corresponding to the 5' non-coding region of the PgD1 (Picea glauca Defensin 1) gene was cloned, characterized, and compared with all Arabidopsis thaliana defensin promoters. The cloned fragment was found to contain several motifs specific to defence or hormonal response, including a motif involved in the methyl jasmonate reponse, a fungal elicitor responsive element, and TC-rich repeat cis-acting element involved in defence and stress responsiveness. A functional analysis of the PgD1 promoter was performed using the uidA (GUS) reporter system in stably transformed Arabidopsis and white spruce plants. The PgD1 promoter was responsive to jasmonic acid (JA), to infection by fungus and to wounding. In transgenic spruce embryos, GUS staining was clearly restricted to the shoot apical meristem. In Arabidopsis, faint GUS coloration was observed in leaves and flowers and a strong blue colour was observed in guard cells and trichomes. Transgenic Arabidopsis plants expressing the PgD1::GUS construct were also infiltrated with the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000. It caused a suppression of defensin expression probably resulting from the antagonistic relationship between the pathogen-stimulated salicylic acid pathway and the jasmonic acid pathway. It is therefore concluded that the PgD1 promoter fragment cloned appears to contain most if not all the elements for proper PgD1 expression and that these elements are also recognized in Arabidopsis despite the phylogenetic and evolutionary differences that separates them.

Diterpene resin acids (DRAs) are specialized (secondary) metabolites of the oleoresin defense of conifers produced by diterpene synthases and cytochrome P450s of the CYP720B family. The evolution of DRA metabolism shares common origins with the biosynthesis of ent-kaurenoic acid, which is highly conserved in general (primary) metabolism of gibberellin biosynthesis. Transcriptome mining in species of spruce (Picea) and pine (Pinus) revealed CYP720Bs of four distinct clades. We cloned a comprehensive set of 12 different Sitka spruce (Picea sitchensis) CYP720Bs as full length cDNAs. Spatial expression profiles, methyl jasmonate induction, and transcript enrichment in terpenoid producing resin ducts suggested a role of CYP720B4 in DRA biosynthesis. CYP720B4 was characterized as a multi-substrate, multi-functional enzyme by: Formation of oxygenated diterpenoids in metabolically engineered yeast, yeast in vivo transformation of diterpene substrates, in vitro assays with CYP720B4 protein produced in E. coli, and alteration of DRA profiles in RNAi suppressed spruce seedlings. CYP720B4 was active with 24 different diterpenoid substrates, catalyzing consecutive C-18 oxidations in the biosynthesis of an array of diterpene alcohols, aldehydes, and acids. CYP720B4 was most active in the formation of dehydroabietic acid, a compound associated with insect resistance of Sitka spruce. We identified patterns of convergent evolution of CYP720B4 in DRA metabolism and ent-kaurene oxidase CYP701 in gibberellin metabolism, and reveal differences in the evolution of specialized and general diterpene metabolism in a gymnosperm. The genomic and functional characterization of the gymnosperm CYP720B family highlight that evolution of specialized metabolism involves substantial diversification relative to conserved, general metabolism..

OBJECTIVE:: To determine whether the survival gains achieved in critically ill cancer patients in recent years exist in the subset with neutropenia and severe sepsis or septic shock. DESIGN:: Retrospective 11-yr study (1998-2008). SETTING:: Medical intensive care unit in a teaching hospital. PATIENTS:: Four hundred twenty-eight intensive care unit patients with cancer, neutropenia, and severe sepsis or septic shock. The primary outcome was hospital mortality. RESULTS:: The main underlying diseases were acute leukemia (35.7%), lymphoma (31.7%), and solid tumors (16.5%). Two hundred thirty-seven (55.5%) patients had microbiologically documented infections, 141 (32.9%) clinically documented infections, and 50 (11.9%) fever of unknown origin. Acute noninfectious conditions were diagnosed in 175 of 428 (41%) patients, including 26 of 50 (52%) patients with fever of unknown origin, 66 of 141 (47%) patients with clinically documented infections, and 83 of 237 (35%) patients with microbiologically documented infections. Early indwelling catheter removal was performed routinely in the 107 (25%) patients without clinical evidence of a septic focus at intensive care unit admission. Early beta-lactam plus aminoglycoside therapy was used in 391 (91.3%) patients. Hospital mortality was 49.8%. Hospital mortality decreased from 58.7%(108 of 184) in 1998-2003 to 43% in 2004-2008 (105 of 244, p =.006). Multivariate analysis identified nine independent predictors of hospital mortality, of which six were associated with higher mortality (older age; need for vasopressors; neurologic, respiratory, or hepatic dysfunction; and acute noninfectious condition) and three with lower mortality (intensive care unit admission after 2003, combination antibiotic therapy including an aminoglycoside, and early indwelling catheter removal). CONCLUSION:: In neutropenic patients with severe sepsis or septic shock, survival improved over time. Aminoglycoside use and early catheter removal in patients with undocumented sepsis may improve survival. Acute noninfectious conditions are associated with increased mortality, underlining the need for thorough and repeated clinical assessments.

MAPKs contribute to the establishment of plant disease resistance by regulating downstream signaling components including transcription factors. In this study, we identified MAPK interacting proteins and among newly discovered candidates was a Cys2/His2-type zinc finger protein named PtiZFP1. This putative transcription factor belongs to a family of transcriptional repressors that rely on an EAR motif for their repression activity. Amino acids located within this repression motif were also found to be essential for MAPK binding. Close examination of the primary protein sequence revealed a functional bipartite MAPK docking site that partially overlaps with the EAR motif. Transient expression assays in Arabidopsis protoplasts suggest that MAPKs promote PtiZFP1 degradation through the 26S proteasome. Since features of MAPK docking site are conserved among other EAR-repressors, our study suggests a novel mode of defense mechanism regulation involving stress responsive MAPKs and EAR-repressors.

We present in this Letter experimental results on the bidimensional flow field around a cylinder penetrating into dense granular matter, together with drag force measurements. A hydrodynamic model based on extended kinetic theory for dense granular flow reproduces well the flow localization close to the cylinder and the corresponding scalings of the drag force, which is found to not depend on velocity, but linearly on the pressure and on the cylinder diameter and weakly on the grain size. Such a regime is found to be valid at a low enough "granular" Reynolds number.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is a life-threatening infection documented in up to 15% of hematology patients who require intensive care for acute respiratory failure. We report outcomes in hematology patients given mechanical ventilation (MV) with IPA. METHODS: Retrospective study of all hematology patients given MV with IPA between January 1998 and March 2011 at a single center. Predictors of 6-month survival or mortality were identified using multivariable analysis. RESULTS: We studied 67 patients including 49 (73%) with neutropenia, 23 (34%) with long-term steroid therapy, and 14 (21%) with allogeneic bone marrow transplantation. Incidence of IPA in the ICU decreased between 1998 and 2011, and mortality in patients receiving mechanical ventilation did not change. IPA was confirmed in 6 patients by autopsy and was probable in 61 patients based on host factors, clinical and radiographic features, and either Aspergillus isolation (50 patients) or Aspergillus antigen detection alone (11 patients). Concomitant bacterial infections were documented in 24 (36%) patients. ICU and 6-month mortality rates were 67 and 82%, respectively. Mortality was stable throughout the study period. Concomitant bacterial infection was independently associated with higher mortality [HR, 2.1 (1.2-3.8)]. Mortality was lower in patients given voriconazole [OR, 0.5 (0.3-0.9)]. CONCLUSION: Hospital mortality remains high in hematology patients requiring MV with IPA, particularly when concommittant infection occurred. The use of voriconazole improved survival.

The use of steroids is not required in myeloid malignancies and remains controversial in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). We sought to evaluate dexamethasone in patients with ALI/ARDS caused by acute monocytic leukaemia (AML FAB-M5) via either leukostasis or leukaemic infiltration. Dexamethasone (10 mg every 6 h until neutropenia) was added to chemotherapy and intensive care unit (ICU) management in 20 consecutive patients between 2005 and 2008, whose data were compared with those from 20 historical controls (1994-2002). ICU mortality was the primary criterion. We also compared respiratory deterioration rates, need for ventilation and nosocomial infections. 17 (85%) patients had hyperleukocytosis, 19 (95%) had leukaemic masses, and all 20 had severe pancytopenia. All patients presented with respiratory symptoms and pulmonary infiltrates prior to AML FAB-M5 diagnosis. Compared with historical controls, dexamethasone-treated patients had a significantly lower ICU mortality rate (20% versus 50%; p = 0.04) and a trend for less respiratory deterioration (50% versus 80%; p = 0.07). There were no significant increases in the rates of infections with dexamethasone. In conclusion, in patients with ALI/ARDS related to AML FAB-M5, adding dexamethasone to conventional chemotherapy seemed effective and safe. These results warrant a controlled trial of dexamethasone versus placebo in AML FAB-M5 patients with noninfectious pulmonary infiltrates.