Ontario children have outgrown the broselow tape

Objective: The Broselow Pediatric Emergency Tape (Armstrong Medical Industries, Inc., Lincolnshire, IL) (BT) is a well-established length-based tool for estimation of body weight for children during resuscitation. In view of pandemic childhood obesity, the BT may no longer accurately estimate weight. We therefore studied the BT in children from Ontario in a large recent patient cohort. Methods: Actual height and weight were obtained from an urban and a rural setting. Children were prospectively recruited between April 2007 and July 2008 from the emergency department and outpatient clinics at the London Health Science Centre. Rural children from junior kindergarten to grade 4 were also recruited in the spring of 2008 from the Avon Maitland District School Board. Data for preschool children were obtained from three daycare centres and the electronic medical record from the Maitland Valley Medical Centre. The predicted weight from the BT was compared to the actual weight using Spearman rank correlation; agreement and percent error (PE) were also calculated. Results: A total of 6,361 children (46.2% female) were included in the study. The median age was 3.9 years (interquartile range [IQR] 1.56-7.67 years), weight was 17.2 kg (IQR 11.6-25.4 kg), and height was 103.5 cm (IQR 82-124.4 cm). Although the BT weight estimate correlated with the actual weight (r = 0.95577, p \u3c 0.0001), the BT underestimated the actual weight by 1.62 kg (7.1% ± 16.9% SD, 95% CI -26.0-40.2). The BT had an ≥ 10% PE 43.7% of the time. Conclusions: Although the BT remains an effective method for estimating pediatric weight, it was not accurate and tended to underestimate the weight of Ontario children. Until more accurate measurement tools for emergency departments are developed, physicians should be aware of this discrepancy. © Canadian Association of Emergency Physicians 2010

Cyst Reduction in a Polycystic Kidney Disease Drosophila Model Using Smac Mimics

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited malady affecting 12.5 million people worldwide. Therapeutic options to treat PKD are limited, due in part to lack of precise knowledge of underlying pathological mechanisms. Mimics of the second mitochondria-derived activator of caspases (Smac) have exhibited activity as antineoplastic agents and reported recently to ameliorate cysts in a murine ADPKD model, possibly by differentially targeting cystic cells and sparing the surrounding tissue. A first-in-kind Drosophila PKD model has now been employed to probe further the activity of novel Smac mimics. Substantial reduction of cystic defects was observed in the Malpighian (renal) tubules of treated flies, underscoring mechanistic conservation of the cystic pathways and potential for efficient testing of drug prototypes in this PKD model. Moreover, the observed differential rescue of the anterior and posterior tubules overall, and within their physiologically diverse intermediate and terminal regions implied a nuanced response in distinct tubular regions contingent upon the structure of the Smac mimic. Knowledge gained from studying Smac mimics reveals the capacity for the Drosophila model to precisely probe PKD pharmacology highlighting the value for such critical evaluation of factors implicated in renal function and pathology

Bicaudal C mutation causes myc and TOR pathway up-regulation and polycystic kidney disease-like phenotypes in Drosophila

Progressive cystic kidney degeneration underlies diverse renal diseases, including the most common cause of kidney failure, autosomal dominant Polycystic Kidney Disease (PKD). Genetic analyses of patients and animal models have identified several key drivers of this disease. The precise molecular and cellular changes underlying cystogenesis remain, however, elusive. Drosophila mutants lacking the translational regulator Bicaudal C (BicC, the fly ortholog of vertebrate BICC1 implicated in renal cystogenesis) exhibited progressive cystic degeneration of the renal tubules (so called ªMalpighianº tubules) and reduced renal function. The BicC protein was shown to bind to Drosophila (d-) myc mRNA in tubules. Elevation of d-Myc protein levels was a cause of tubular degeneration in BicC mutants. Activation of the Target of Rapamycin (TOR) kinase pathway, another common feature of PKD, was found in BicC mutant flies. Rapamycin administration substantially reduced the cystic phenotype in flies. We present new mechanistic insight on BicC function and propose that Drosophila may serve as a genetically tractable model for dissecting the evolutionarily-conserved molecular mechanisms of renal cystogenesis

CD36 plays an important role in the clearance of oxLDL and associated age-dependent sub-retinal deposits

Age-related macular degeneration (AMD) represents the major cause of vision loss in industrialized nations. Laminar deposits in Bruch's membrane (BM) are among the first prominent histopathologic features, along with drusen formation, and have been found to contain oxidized lipids. Increases in concentrations of oxidized LDL (oxLDL) in plasma are observed with age and high fat high (HFHC) cholesterol diet. CD36 is the principal receptor implicated in uptake of oxLDL, and is expressed in the retinal pigment epithelium (RPE). We determined if CD36 participates in oxLDL uptake in RPE and correspondingly in clearance of sub-retinal deposits. Uptake of oxLDL by RPE in vitro and in vivo was CD36-dependent. CD36 deficiency in mice resulted in age-associated accumulation of oxLDL and sub-retinal BM thickening, despite fed a regular diet. Conversely, treatment of HFHC-fed ApoE null mice with a CD36 agonist, EP80317 (300 μg/kg/day), markedly diminished thickening of BM, and partially preserved (in part) photoreceptor function. In conclusion, our data uncover a new role for CD36 in the clearance of oxidized lipids from BM and in the prevention of age-dependent sub-retinal laminar deposits

Agricultural mitigation and adaptation to climate change in Yolo County, CA

This place‐based case study in an agricultural county in California’s Central Valley focused on the period of 2010–2050, and dealt with biophysical and socioeconomic issues related to both mitigation of greenhouse gas (GHG) emissions and to adaptation to an uncertain climate. In the past 100 years, changes in crop acreage has been more related to crop price and availability of irrigation water than to growing degree days during summer, and in fact, summer temperatures have increased less than winter temperatures. Econometric analysis indicated that warmer winters, as projected by Geophysical Fluid Dynamics Laboratory‐Bias Corrected Constructed Analog during 2035–2050, could result in less wheat acreage, more alfalfa and tomato acreage, and slight effects on tree and vine crops. The Water Evaluation and Planning (WEAP) model showed that these econometric projections did not reduce irrigation demand under either the B1 or A2 scenarios, but a diverse, water‐efficient cropping pattern combined with improved irrigation technology reduced demand to 12 percent below the historic mean. Collaboration during development of Yolo County’s Climate Action Plan showed that nitrous oxide (mainly from nitrogen fertilizers) was the main source (≅40 percent) of agricultural emissions. Emissions from cropland and rangeland were several orders of magnitude lower than urbanized land per unit area. A survey distributed to 570 farmers and ranchers achieved a 34 percent response rate. Farmers concerned about climate change were more likely to implement water conservation practices, and adopt voluntary GHG mitigation practices. Use of the urban growth model (UPlan) showed that channeling much or all future urban development into existing urban areas will increase ecosystem services by preserving agricultural land and open space, immensely reducing the Yolo County’s GHG emissions, and greatly enhancing agricultural sustainability

Planning for Sustainability in Small Municipalities: The Influence of Interest Groups, Growth Patterns, and Institutional Characteristics

How and why small municipalities promote sustainability through planning efforts is poorly understood. We analyzed ordinances in 451 Maine municipalities and tested theories of policy adoption using regression analysis.We found that smaller communities do adopt programs that contribute to sustainability relevant to their scale and context. In line with the political market theory, we found that municipalities with strong environmental interests, higher growth, and more formal governments were more likely to adopt these policies. Consideration of context and capacity in planning for sustainability will help planners better identify and benefit from collaboration, training, and outreach opportunities

Influence of N- methylation and conformation on almiramide anti-leishmanial activity

The almiramide N-methylated lipopeptides exhibit promising activity against trypanosomatid parasites. A structure–activity relationship study has been performed to examine the influences of N-methylation and conformation on activity against various strains of leishmaniasis protozoan and on cytotoxicity. The synthesis and biological analysis of twenty-five analogs demonstrated that derivatives with a single methyl group on either the first or fifth residue amide nitrogen exhibited greater activity than the permethylated peptides and relatively high potency against resistant strains. Replacement of amino amide residues in the peptide, by turn inducing α‑amino γ‑lactam (Agl) and N-aminoimidazalone (Nai) counterparts, reduced typically anti-parasitic activity; however, peptide amides possessing Agl residues at the second residue retained significant potency in the unmethylated and permethylated series. Systematic study of the effects of methylation and turn geometry on anti-parasitic activity indicated the relevance of an extended conformer about the central residues, and conformational mobility by tertiary amide isomerization and turn geometry at the extremities of the active peptides

Climate-smart agriculture global research agenda: Scientific basis for action

Background: Climate-smart agriculture (CSA) addresses the challenge of meeting the growing demand for food, fibre and fuel, despite the changing climate and fewer opportunities for agricultural expansion on additional lands. CSA focuses on contributing to economic development, poverty reduction and food security; maintaining and enhancing the productivity and resilience of natural and agricultural ecosystem functions, thus building natural capital; and reducing trade-offs involved in meeting these goals. Current gaps in knowledge, work within CSA, and agendas for interdisciplinary research and science-based actions identified at the 2013 Global Science Conference on Climate-Smart Agriculture (Davis, CA, USA) are described here within three themes: (1) farm and food systems, (2) landscape and regional issues and (3) institutional and policy aspects. The first two themes comprise crop physiology and genetics, mitigation and adaptation for livestock and agriculture, barriers to adoption of CSA practices, climate risk management and energy and biofuels (theme 1); and modelling adaptation and uncertainty, achieving multifunctionality, food and fishery systems, forest biodiversity and ecosystem services, rural migration from climate change and metrics (theme 2). Theme 3 comprises designing research that bridges disciplines, integrating stakeholder input to directly link science, action and governance. Outcomes: In addition to interdisciplinary research among these themes, imperatives include developing (1) models that include adaptation and transformation at either the farm or landscape level; (2) capacity approaches to examine multifunctional solutions for agronomic, ecological and socioeconomic challenges; (3) scenarios that are validated by direct evidence and metrics to support behaviours that foster resilience and natural capital; (4) reductions in the risk that can present formidable barriers for farmers during adoption of new technology and practices; and (5) an understanding of how climate affects the rural labour force, land tenure and cultural integrity, and thus the stability of food production. Effective work in CSA will involve stakeholders, address governance issues, examine uncertainties, incorporate social benefits with technological change, and establish climate finance within a green development framework. Here, the socioecological approach is intended to reduce development controversies associated with CSA and to identify technologies, policies and approaches leading to sustainable food production and consumption patterns in a changing climate

Review of research to inform California's climate scoping plan: Agriculture and working lands

Agriculture in California contributes 8% of the state's greenhouse gas (GHG) emissions. To inform the state's policy and program strategy to meet climate targets, we review recent research on practices that can reduce emissions, sequester carbon and provide other co-benefits to producers and the environment across agriculture and rangeland systems. Importantly, the research reviewed here was conducted in California and addresses practices in our specific agricultural, socioeconomic and biophysical environment. Farmland conversion and the dairy and intensive livestock sector are the largest contributors to GHG emissions and offer the greatest opportunities for avoided emissions. We also identify a range of other opportunities including soil and nutrient management, integrated and diversified farming systems, rangeland management, and biomass-based energy generation. Additional research to replicate and quantify the emissions reduction or carbon sequestration potential of these practices will strengthen the evidence base for California climate policy

Probing Anti-inflammatory Properties Independent of NF-κB Through Conformational Constraint of Peptide-Based Interleukin-1 Receptor Biased Ligands

Interleukin-1β (IL-1β) binds to the IL-1 receptor (IL-1R) and is a key cytokine mediator of inflammasome activation. IL-1β signaling leads to parturition in preterm birth (PTB) and contributes to the retinal vaso-obliteration characteristic of oxygen-induced retinopathy (OIR) of premature infants. Therapeutics targeting IL-1β and IL-1R are approved to treat rheumatoid arthritis; however, all are large proteins with clinical limitations including immunosuppression, due in part to inhibition of NF-κB signaling, which is required for immuno-vigilance and cytoprotection. The all-D-amino acid peptide 1 (101.10, H-d-Arg-d-Tyr-d-Thr-d-Val-d-Glu-d-Leu-d-Ala-NH2) is an allosteric IL-1R modulator, which exhibits functional selectivity and conserves NF-κB signaling while inhibiting other IL-1-activated pathways. Peptide 1 has proven effective in experimental models of PTB and OIR. Seeking understanding of the structural requirements for the activity and biased signaling of 1, a panel of twelve derivatives was synthesized employing the various stereochemical isomers of α-amino-γ-lactam (Agl) and α-amino-β-hydroxy-γ-lactam (Hgl) residues to constrain the D-Thr-D-Val dipeptide residue. Using circular dichroism spectroscopy, the peptide conformation in solution was observed to be contingent on Agl, Hgl, and Val stereochemistry. Moreover, the lactam mimic structure and configuration influenced biased IL-1 signaling in an in vitro panel of cellular assays as well as in vivo activity in murine models of PTB and OIR. Remarkably, all Agl and Hgl analogs of peptide 1 did not inhibit NF-κB signaling but blocked other pathways, such as JNK and ROCK2 phosphorylation contingent on structure and configuration. Efficacy in preventing preterm labor correlated with a capacity to block IL-1β-induced IL-1β synthesis. Furthermore, the importance of inhibition of JNK and ROCK2 phosphorylation for enhanced activity was highlighted for prevention of vaso-obliteration in the OIR model. Taken together, lactam mimic structure and stereochemistry strongly influenced conformation and biased signaling. Selective modulation of IL-1 signaling was proven to be particularly beneficial for curbing inflammation in models of preterm labor and retinopathy of prematurity (ROP). A class of biased ligands has been created with potential to serve as selective probes for studying IL-1 signaling in disease. Moreover, the small peptide mimic prototypes are promising leads for developing immunomodulatory therapies with easier administration and maintenance of beneficial effects of NF-κB signaling