Gadolinium in pediatric cardiovascular magnetic resonance: what we know and how we practice

BACKGROUND: The association of gadolinium-based contrast agents (GBCAs) with nephrogenic systemic fibrosis (NSF) has led to a heightened awareness towards patients’ renal function. Whereas detailed guidelines exist for the use of GBCAs in adult patients, best practice is less well defined in children, especially in the very young. We aimed at identifying current practice with regards to the use of GBCAs in children who undergo Cardiovascular Magnetic Resonance. METHODS: We conducted a worldwide survey among cardiac imagers with pediatric expertise. The questionnaire contained 21 questions covering the imagers’ work environments, GBCAs used, monitoring of renal function, and a special emphasis was placed on the practice in neonates. RESULTS: The survey yielded 70 replies. The single most commonly used GBCA was gadopentetate dimeglumine 34/70 (49%). Among the respondents, the choice of GBCA was more importantly based on availability 26/70 (37%) and approval by a pharmaceutical licensing body that most closely reflects the indication 16/70 (23%) than image quality 7/70 (10%) and side effect profile 8/70 (11%). 55/70 (79%) of respondents performed scans in neonates <1 week of age and 52/55 (95%) of them used GBCA in neonates. 65/70 (93%) respondents at least assess some of their patients’ renal functions. Formula-based estimate of glomerular filtration rate is the most popular assessment method 35/65 (54%). In patients with a glomerular filtration rate < 30 ml/min/1.73 m(2) 62/70 (89%) of respondents do not administer gadolinium at all. The single most common side effect of gadolinium was noted to be nausea/emesis 34/57 (60%) followed by discomfort at injection site 17/57 (30%). CONCLUSIONS: Cardiac imagers are aware of the immature renal function and physiological differences of their pediatric patients that place them at risk for NSF. Epidemiological data is needed for pediatric cardiovascular licensure of gadolinium compounds and for the creation of practice guidelines which will replace current-day practice based on individual clinical judgment

Osteoporosis Prevention—A Worthy and Achievable Strategy

This special issue of Nutrients records seven of the presentations made to the very successful meeting titled “Osteoporosis Prevention: A Workshop on Calcium, Vitamin D and other Nutritional Aspects” held in Adelaide, Australia on 5 and 6 March 2010 [1-7]. Seventy six delegates attended from across Australia and New Zealand to review the current evidence that dietary calcium intake, vitamin D status, other nutrients and exercise play a significant role in bone mineral homeostasis and act to prevent the development of osteoporosis. The Workshop promoted the concept that osteoporosis is a predictable and preventable disease and that significant benefit would be achieved to reduce the incidence of osteoporosis and the risk of fractures from nutrition and life style activities. Such an achievement will not only save considerable pain, suffering and morbidity but will also have a major financial benefit for the healthcare system for which the cost of treatment for osteoporotic fractures already amounts to billions of dollars

A single protein S-acyl transferase acts through diverse substrates to determine cryptococcal morphology, stress tolerance, and pathogenic outcome

Cryptococcus neoformans is an opportunistic yeast that kills over 625,000 people yearly through lethal meningitis. Host phagocytes serve as the first line of defense against this pathogen, but fungal engulfment and subsequent intracellular proliferation also correlate with poor patient outcome. Defining the interactions of this facultative intracellular pathogen with host phagocytes is key to understanding the latter's opposing roles in infection and how they contribute to fungal latency, dissemination, and virulence. We used high-content imaging and a human monocytic cell line to screen 1,201 fungal mutants for strains with altered host interactions and identified multiple genes that influence fungal adherence and phagocytosis. One of these genes was PFA4, which encodes a protein S-acyl transferase (PAT), one of a family of DHHC domain-containing proteins that catalyzes lipid modification of proteins. Deletion of PFA4 caused dramatic defects in cryptococcal morphology, stress tolerance, and virulence. Bioorthogonal palmitoylome-profiling identified Pfa4-specific protein substrates involved in cell wall synthesis, signal transduction, and membrane trafficking responsible for these phenotypic alterations. We demonstrate that a single PAT is responsible for the modification of a subset of proteins that are critical in cryptococcal pathogenesis. Since several of these palmitoylated substrates are conserved in other pathogenic fungi, protein palmitoylation represents a potential avenue for new antifungal therapeutics

Completely Positive Maps and Classical Correlations

We expand the set of initial states of a system and its environment that are known to guarantee completely positive reduced dynamics for the system when the combined state evolves unitarily. We characterize the correlations in the initial state in terms of its quantum discord [H. Ollivier and W. H. Zurek, Phys. Rev. Lett. 88, 017901 (2001)]. We prove that initial states that have only classical correlations lead to completely positive reduced dynamics. The induced maps can be not completely positive when quantum correlations including, but not limited to, entanglement are present. We outline the implications of our results to quantum process tomography experiments.Comment: 4 pages, 1 figur

Group IIa secretory phospholipase expression correlates with group IIa secretory phospholipase inhibition–mediated cell death in K-ras mutant lung cancer cells

ObjectiveThere are currently no targeted therapies against lung tumors with oncogenic K-ras mutations that are found in 25% to -40% of lung cancers and are characterized by their resistance to epidermal growth factor receptor inhibitors. The isozyme group IIa secretory phospholipase A2 (sPLA2IIa) is a potential biomarker and regulator of lung cancer cell invasion; however, the relationship between K-ras mutations and sPLA2IIa has yet to be investigated. We hypothesize that sPLA2IIa modulates lung cancer cell growth in K-ras mutant cells and that sPLA2IIa expression in human lung tumors is increased in K-ras mutant tumors.MethodsBaseline sPLA2IIa expression in K-ras mutant lung cancer cell lines (A549, SW1573, H358, H2009) was assessed. Cells were treated with a specific sPLA2IIa inhibitor and evaluated for apoptosis and cell viability. Nuclear factor kappa-b (NF-κB) and extracellular signal-regulated kinase 1/2 activity were detected by Western blot. Human tumor samples were evaluated for sPLA2IIa mRNA expression by quantitative reverse-transcription polymerase chain reaction.ResultsCytotoxicity of sPLA2IIa inhibition correlates with sPLA2IIa expression. Apoptosis in response to sPLA2 inhibition parallels attenuation in NF-κB activity. In addition, sPLA2IIa expression in human tumors correlates with squamous cell pathology and increasing stage of K-ras mutant lung tumors.ConclusionsBaseline sPLA2IIa expression predicts response to sPLA2IIa inhibition in some K-ras mutant lung cancer cells. This finding is independent of p53 mutation status. Furthermore, squamous tumors and advanced-stage K-ras mutant tumors express more sPLA2IIa. These data support a role for sPLA2IIa as a potential global therapeutic target in the treatment of lung cancer

Age Adjusted Hematopoietic Stem Cell Transplant Comorbidity Index Predicts Survival in a T-Cell Depleted Cohort

Objectives: Allogeneic hematopoietic stem cell transplant (HCT) continues to evolve with the treatment in higher risk patient population. This practice mandates stringent update and validation of risk stratification prior to undergoing such a complex and potentially fatal procedure. We examined the adoption of the new comorbidity index (HCT-CI/Age) proposed by the Seattle group after the addition of age variable and compared it to the pre-transplant assessment of mortality (PAM) that already incorporates age as part of its evaluation criteria. Methods: A retrospective analysis of adult patients who underwent HCT at our institution from January 2010 through August 2014 was performed. Kaplan-Meier’s curve, log-rank tests, Cox model and Pearson correlation was used in the analysis. Results: Of the 114 patients that underwent allogeneic transplant in our institution, 75.4% were ≥ 40 years old. More than 58% had a DLCO ≤ 80%. Although scores were positively correlated (correlation coefficient 0.43, p \u3c 0.001), HCT-CI/Age more accurately predicted 2-year overall survival (OS) and non-relapse mortality (NRM) in patients with lower (0–4) and higher (5–7) scores (52% and 36% versus 24% and 76%, p = 0.004, 0.003 respectively). PAM score did not reach statistical significance for difference in OS nor NRM between the low (\u3c 24) and high-risk (≥ 24) groups (p = 0.19 for both). Conclusions: Despite our small sample population, HCT-CI/Age was more discriminative to identify patients with poor outcome that might benefit from intensified management strategies or other therapeutic approaches rather than allogeneic HCT

A Roadmap for Lowering Crop Nitrogen Requirement.

Increasing nitrogen fertilizer applications have sustained a growing world population in the 20th century. However, to avoid any further associated environmental damage, new sustainable agronomic practices together with new cultivars must be developed. To date the concept of nitrogen use efficiency (NUE) has been useful in quantifying the processes of nitrogen uptake and utilization, but we propose a shift in focus to consider nitrogen responsiveness as a more appropriate trait to select varieties with lower nitrogen requirements. We provide a roadmap to integrate the regulation of nitrogen uptake and assimilation into varietal selection and crop breeding programs. The overall goal is to reduce nitrogen inputs by farmers growing crops in contrasting cropping systems around the world, while sustaining yields and reducing greenhouse gas (GHG) emissions

A Foundational View on Integration Problems

The integration of reasoning and computation services across system and language boundaries is a challenging problem of computer science. In this paper, we use integration for the scenario where we have two systems that we integrate by moving problems and solutions between them. While this scenario is often approached from an engineering perspective, we take a foundational view. Based on the generic declarative language MMT, we develop a theoretical framework for system integration using theories and partial theory morphisms. Because MMT permits representations of the meta-logical foundations themselves, this includes integration across logics. We discuss safe and unsafe integration schemes and devise a general form of safe integration