Effect of Long-Term Nutrient Management Strategies for Pastures on Phosphorus in Surface Runoff and Soil Quality

Manure, whether mechanically applied or deposited by grazing animals, has been associated with increased risk of non-point source pollution, especially phosphorus. This is especially true in areas where the industry, especially poultry, has been concentrated in geographical areas that are grain deficient, resulting in a reliance on imported grain for poultry feed. Intensification has resulted in the production of large quantities of poultry manure, within relatively small geographical areas. Surplus litter is typically land applied as a nutrient source or used as an animal feed. The objective of this project was to evaluate the effects of long-term nutrient management strategies using poultry litter as a feed and fertiliser for grazed pasture systems in the Shenandoah Valley of Virginia on soil quality, selected soil chemical characteristics and P losses in surface runoff

A bioluminescent microbial biosensor for in vitro pretreatment assessment of cytarabine efficacy in leukemia

BACKGROUND: The nucleoside analog cytarabine (Ara-C [cytosine arabinoside]) is the key agent for treating acute myeloid leukemia (AML); however, up to 30% of patients fail to respond to treatment. Screening of patient blood samples to determine drug response before commencement of treatment is needed. This project aimed to construct and evaluate a self-bioluminescent reporter strain of Escherichia coli for use as an Ara-C biosensor and to design an in vitro assay to predict Ara-C response in clinical samples. METHODS: Weused transposition mutagenesis to create a cytidine deaminase (cdd)-deficient mutant of E. coli MG1655 that responded to Ara-C. The strain was transformed with the luxCDABE operon and used as a whole-cell biosensor for development an 8-h assay to determine Ara-C uptake and phosphorylation by leukemic cells. RESULTS: Intracellular concentrations of 0.025 μmol/L phosphorylated Ara-C were detected by significantly increased light output (P < 0.05) from the bacterial biosensor. Results using AML cell lines with known response to Ara-C showed close correlation between the 8-h assay and a 3-day cytotoxicity test for Ara-C cell killing. In retrospective tests with 24 clinical samples of bone marrow or peripheral blood, the biosensor-based assay predicted leukemic cell response to Ara-C within 8 h. CONCLUSIONS: The biosensor-based assay may offer a predictor for evaluating the sensitivity of leukemic cells to Ara-C before patients undergo chemotherapy and allow customized treatment of drug-sensitive patients with reduced Ara-C dose levels. The 8-h assay monitors intracellular Ara-CTP (cytosine arabinoside triphosphate) levels and, if fully validated, may be suitable for use in clinical settings. © 2010 American Association for Clinical Chemistry

Perspectives of frontline professionals on Palestinian children's experiences of parental and sibling drug abuse in the West Bank and Gaza.

The Occupied Territories of Palestine (OtP) consists of the non-contiguous West Bank including East Jerusalem, and the Gaza Strip. Political and economic tensions and its dense populations compounds the impact of drug abuse and addiction in the home. A qualitative study using four focus groups (n=42) was conducted in West Bank and Gaza Strip explored the experiences of professionals working with Palestinian families and children affected by substance use and addiction in the home. Data were analysed using thematic analysis (TA), and four themes emerged. These were ‘The rising and shifting problem of drug use in Palestine’; ‘Psychosocial causal factors of drug use in Palestine’; ‘The consequences for children and families living with drug use’; and ‘Potential solutions to the problem are complex and multi-faceted.’ The study paints a concerning picture of how drug abuse impacts on Palestinian families subjected to multiple pressures, stigmas, risks and harms relating to their situation

Characterizing the Role of Cell-Wall β-1,3-Exoglucanase Xog1p in Candida albicans Adhesion by the Human Antimicrobial Peptide LL-37

Candida albicans is the major fungal pathogen of humans. Its adhesion to host-cell surfaces is the first critical step during mucosal infection. Antimicrobial peptides play important roles in the first line of mucosal immunity against C. albicans infection. LL-37 is the only member of the human cathelicidin antimicrobial peptide family and is commonly expressed in various tissues, including epithelium. We previously showed that LL-37 significantly reduced C. albicans adhesion to plastic, oral epidermoid OECM-1 cells, and urinary bladders of female BALB/c mice. The inhibitory effect of LL-37 on cell adhesion occurred via the binding of LL-37 to cell-wall carbohydrates. Here we showed that formation of LL-37–cell-wall protein complexes potentially inhibits C. albicans adhesion to polystyrene. Using phage display and ELISA, we identified 10 peptide sequences that could bind LL-37. A BLAST search revealed that four sequences in the major C. albicans cell-wall β-1,3-exoglucanase, Xog1p, were highly similar to the consensus sequence derived from the 10 biopanned peptides. One Xog1p-derived peptide, Xog1p90–115, and recombinant Xog1p associated with LL-37, thereby reversing the inhibitory effect of LL-37 on C. albicans adhesion. LL-37 reduced Xog1p activity and thus interrupted cell-wall remodeling. Moreover, deletion of XOG1 or another β-1,3-exoglucanase-encoding gene EXG2 showed that only when XOG1 was deleted did cellular exoglucanase activity, cell adhesion and LL-37 binding decrease. Antibodies against Xog1p also decreased cell adhesion. These data reveal that Xog1p, originally identified from LL-37 binding, has a role in C. albicans adhesion to polystyrene and, by inference, attach to host cells via direct or indirect manners. Compounds that target Xog1p might find use as drugs that prevent C. albicans infection. Additionally, LL-37 could potentially be used to screen for other cell-wall components involved in fungal cell adhesion

Enhanced recovery programmes for lower limb arthroplasty in the UK

Introduction: Enhanced recovery programmes (ERPs) reduce patient morbidity and mortality, and provide significant cost savings by reducing length of stay. Currently, no uniform ERP guidelines exist for lower limb arthroplasty in the UK. The aim of this study was to identify variations in ERPs and determine adherence to local policy. Methods: Hospitals offering elective total knee arthroplasty (TKA) and total hip arthroplasty (THA) (23 and 22 centres respectively) contributed details of their ERPs, and performed an audit (15 patients per centre) to assess compliance. Results: Contrasting content and detail of ERPs was noted across centres. Adherence to ERPs varied significantly (40–100% for TKA, 17–94% for THA). Analysis identified perioperative use of dexamethasone, tranexamic acid and early mobilisation for TKA, and procedures performed in teaching hospitals for THA as being associated with a reduced length of stay. Conclusions: This study highlights variation in practice and poor compliance with local ERPs. Given the proven benefits of ERPs, evidence-based guidelines in the context of local skillsets should be established to optimise the patient care pathway

Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL

Microenvironment and activation signals likely imprint heterogeneity in the lymphatic endothelial cell (LEC) population. Particularly LECs of secondary lymphoid organs are exposed to different cell types and immune stimuli. However, our understanding of the nature of LEC activation signals and their cell source within the secondary lymphoid organ in the steady state remains incomplete. Here we show that integrin alpha 2b (ITGA2b), known to be carried by platelets, megakaryocytes and hematopoietic progenitors, is expressed by a lymph node subset of LECs, residing in medullary, cortical and subcapsular sinuses. In the subcapsular sinus, the floor but not the ceiling layer expresses the integrin, being excluded from ACKR4+LECs but overlapping with MAdCAM-1 expression. ITGA2b expression increases in response to immunization, raising the possibility that heterogeneous ITGA2b levels reflect variation in exposure to activation signals. We show that alterations of the level of receptor activator of NF-κB ligand (RANKL), by overexpression, neutralization or deletion from stromal marginal reticular cells, affected the proportion of ITGA2b+LECs. Lymph node LECs but not peripheral LECs express RANK. In addition, we found that lymphotoxin-β receptor signaling likewise regulated the proportion of ITGA2b+LECs. These findings demonstrate that stromal reticular cells activate LECs via RANKL and support the action of hematopoietic cell-derived lymphotoxin