Tranexamic acid increases early perioperative functional outcomes after total knee arthroplasty.

Background: The purpose of this study was to investigate the influence of tranexamic acid (TXA) on functional outcomes in the immediate postoperative period after total knee arthroplasty (TKA). We hypothesized that the known benefits of TXA would confer measurable clinical improvements in physical therapy (PT) performance, decrease pain, and decrease hospital length of stay (LOS). Methods: We retrospectively analyzed 560 TKA patients, including 280 consecutive patients whose surgery was performed before the initiation of a standardized TXA protocol and the first 280 patients who received TXA after protocol initiation. Outcome measurements included postoperative changes in hemoglobin and hematocrit, LOS, pain scores, destination of discharge, and steps ambulated with PT over 5 sessions. Results: TXA administration resulted in less overall drops in hemoglobin ( Conclusions: It is well known that TXA reduces postoperative anemia, but this study also demonstrates that it confers early perioperative functional benefits for TKA patients. Potential mechanisms for this benefit include reduced rates of postoperative anemia and reduced rates of hemarthroses

Genomic and evolutionary inferences between American and global strains of porcine epidemic diarrhea virus

AbstractPorcine epidemic diarrhea virus (PEDV) has caused severe economic losses both recently in the United States (US) and historically throughout Europe and Asia. Traditionally, analysis of the spike gene has been used to determine phylogenetic relationships between PEDV strains. We determined the complete genomes of 93 PEDV field samples from US swine and analyzed the data in conjunction with complete genome sequences available from GenBank (n=126) to determine the most variable genomic areas. Our results indicate high levels of variation within the ORF1 and spike regions while the C-terminal domains of structural genes were highly conserved. Analysis of the Receptor Binding Domains in the spike gene revealed a limited number of amino acid substitutions in US strains compared to Asian strains. Phylogenetic analysis of the complete genome sequence data revealed high rates of recombination, resulting in differing evolutionary patterns in phylogenies inferred for the spike region versus whole genomes. These finding suggest that significant genetic events outside of the spike region have contributed to the evolution of PEDV

J-matrix method of scattering in any L2 basis

The restriction imposed on the J-matrix method of using specific L2 bases is lifted without compromising any of the advantages that it offers. This opens the door to a wider range of application of the method to physical problems beyond the restrictive SO(2,1) dynamical symmetry. The numerical scheme developed to achieve this objective projects the J-matrix formalism in terms of the eigenvalues of a finite Hamiltonian matrix and its submatrices in any convenient L2 basis. Numerical stability and convergence of the original analytic J-matrix method is still maintained in the proposed scheme, which can be applied to multi-channel nonrelativistic as well as relativistic scattering problems

Identification of Achaete-scute complex-like 1 (ASCL1) target genes and evaluation of DKK1 and TPH1 expression in pancreatic endocrine tumours

<p>Abstract</p> <p>Background</p> <p><it>ASCL1 </it>role in pancreatic endocrine tumourigenesis has not been established. Recently it was suggested that ASCL1 negatively controls expression of the Wnt signalling antagonist <it>DKK1</it>. Notch signalling regulates expression of TPH1, the rate limiting enzyme in the biosyntesis of serotonin. Understanding the development and proliferation of pancreatic endocrine tumours (PETs) is essential for the development of new therapies.</p> <p>Methods</p> <p><it>ASCL1 </it>target genes in the pancreatic endocrine tumour cell line BON1 were identified by RNA interference and microarray expression analysis. Protein expressions of selected target genes in PETs were evaluated by immunohistochemistry.</p> <p>Results</p> <p>158 annotated <it>ASCL1 </it>target genes were identified in BON1 cells, among them DKK1 and TPH1 that were negatively regulated by ASCL1. An inverse relation of ASCL1 to DKK1 protein expression was observed for 15 out of 22 tumours (68%). Nine tumours displayed low ASCL1/high DKK1 and six tumours high ASCL1/low DKK1 expression. Remaining PETs showed high ASCL1/high DKK1 (n = 4) or low ASCL1/low DKK1 (n = 3) expression. Nine of twelve analysed PETs (75%) showed TPH1 expression with no relation to ASCL1.</p> <p>Conclusion</p> <p>A number of genes with potential importance for PET tumourigenesis have been identified. <it>ASCL1 </it>negatively regulated the Wnt signalling antagonist <it>DKK1</it>, and <it>TPH1 </it>expression in BON1 cells. In concordance with these findings DKK1 showed an inverse relation to ASCL1 expression in a subset of PETs, which may affect growth control by the Wnt signalling pathway.</p

Regulatory feedback response mechanisms to phosphate starvation in rice

Phosphorus is a growth-limiting nutrient for plants. The growing scarcity of phosphate stocks threatens global food security. Phosphate-uptake regulation is so complex and incompletely known that attempts to improve phosphorus use efficiency have had extremely limited success. This study improves our understanding of the molecular mechanisms underlying phosphate uptake by investigating the transcriptional dynamics of two regulators: the Ubiquitin ligase PHO2 and the long non-coding RNA IPS1. Temporal measurements of RNA levels have been integrated into mechanistic mathematical models using advanced statistical techniques. Models based solely on current knowledge could not adequately explain the temporal expression profiles. Further modeling and bioinformatics analysis have led to the prediction of three regulatory features: the PHO2 protein mediates the degradation of its own transcriptional activator to maintain constant PHO2 mRNA levels; the binding affinity of the transcriptional activator of PHO2 is impaired by a phosphate-sensitive transcriptional repressor/inhibitor; and the extremely high levels of IPS1 and its rapid disappearance upon Pi re-supply are best explained by Pi-sensitive RNA protection. This work offers both new opportunities for plant phosphate research that will be essential for informing the development of phosphate efficient crop varieties, and a foundation for the development of models integrating phosphate with other stress responses

In situ predatory behavior of Mysis relicta in Lake Michigan

Selectivity coefficients (W′) and predation rates on Lake Michigan zooplankton were determined for Mysis relicta during spring through fall using an in situ method. W′ values indicated the following ranked order of prey preference: Cladocera > copepod copepodites and copepod nauplii > adult diaptomids and cyclopoids. With few exceptions, W′ values for different prey categories remained fairly constant despite greatly changing relative abundances of prey. Predation rates and prey selectivity were similar in most cases to those determined in laboratory studies. Ingestion rates (percent dry body weight · day −1 ) were correlated to total prey biomass (r = 0.38) and to effective prey biomass (r = 0.85), where the weighting factors were overall mean selectivity coefficients for the different prey categories. This result suggested that seasonally varying composition of prey caused much of the variation in ingestion rates among experiments. Feeding trials performed at the same depth with daytime and nighttime assemblages of zooplankton indicated that Cladocera may escape heavy Mysis predation at night by migrating from the metalimnetic-hypolimnetic interface into the epilimnion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42918/1/10750_2004_Article_BF00008105.pd

Spanish Mediterranean diet and other dietary patterns and breast cancer risk: case–control EpiGEICAM study

Background:Although there are solid findings regarding the detrimental effect of alcohol consumption, the existing evidence on the effect of other dietary factors on breast cancer (BC) risk is inconclusive. This study aimed to evaluate the association between dietary patterns and risk of BC in Spanish women, stratifying by menopausal status and tumour subtype, and to compare the results with those of Alternate Healthy Index (AHEI) and Alternate Mediterranean Diet Score (aMED).Methods:We recruited 1017 incident BC cases and 1017 matched healthy controls of similar age (±5 years) without a history of BC. The association between ‘a priori' and ‘a posteriori' developed dietary patterns and BC in general and according to menopausal status and intrinsic tumour subtypes (ER+/PR+ and HER2− HER2+ and ER−/PR− and HER2−) was evaluated using logistic and multinomial regression models.Results:Adherence to the Western dietary pattern was related to higher risk of BC (OR for the top vs the bottom quartile 1.46 (95% CI 1.06–2.01)), especially in premenopausal women (OR=1.75; 95% CI 1.14–2.67). In contrast, the Mediterranean pattern was related to a lower risk (OR for the top quartile vs the bottom quartile 0.56 (95% CI 0.40–0.79)). Although the deleterious effect of the Western pattern was similarly observed in all tumour subtypes, the protective effect of our Mediterranean pattern was stronger for triple-negative tumours (OR=0.32; 95% CI 0.15–0.66 and Pheterogeneity=0.04). No association was found between adherence to the Prudent pattern and BC risk. The associations between ‘a priori' indices and BC risk were less marked (OR for the top vs the bottom quartile of AHEI=0.69; 95% CI 0.51–0.94 and aMED=0.74; 95% CI 0.46–1.18)).Conclusions:Our results confirm the harmful effect of a Western diet on BC risk, and add new evidence on the benefits of a diet rich in fruits, vegetables, legumes, oily fish and vegetable oils for preventing all BC subtypes, and particularly triple-negative tumours

Predicting Pancreas Cell Fate Decisions and Reprogramming with a Hierarchical Multi-Attractor Model

Cell fate reprogramming, such as the generation of insulin-producing β cells from other pancreas cells, can be achieved by external modulation of key transcription factors. However, the known gene regulatory interactions that form a complex network with multiple feedback loops make it increasingly difficult to design the cell reprogramming scheme because the linear regulatory pathways as schemes of causal influences upon cell lineages are inadequate for predicting the effect of transcriptional perturbation. However, sufficient information on regulatory networks is usually not available for detailed formal models. Here we demonstrate that by using the qualitatively described regulatory interactions as the basis for a coarse-grained dynamical ODE (ordinary differential equation) based model, it is possible to recapitulate the observed attractors of the exocrine and β, δ, α endocrine cells and to predict which gene perturbation can result in desired lineage reprogramming. Our model indicates that the constraints imposed by the incompletely elucidated regulatory network architecture suffice to build a predictive model for making informed decisions in choosing the set of transcription factors that need to be modulated for fate reprogramming

Modulation of macrophage cytokine profiles during solid tumor progression: susceptibility to Candida albicans infection

<p>Abstract</p> <p>Background</p> <p>In order to attain a better understanding of the interactions between opportunist fungi and their hosts, we investigated the cytokine profile associated with the inflammatory response to <it>Candida albicans </it>infection in mice with solid Ehrlich tumors of different degrees.</p> <p>Methods</p> <p>Groups of eight animals were inoculated intraperitoneally with 5 × 10⁶<it>C. albicans </it>7, 14 or 21 days after tumor implantation. After 24 or 72 hours, the animals were euthanized and intraperitoneal lavage fluid was collected. Peritoneal macrophages were cultivated and the levels of IFN-γ, TNF-α, IL-12, IL-10 and IL-4 released into the supernatants were measured by ELISA. Kidney, liver and spleen samples were evaluated for fungal dissemination. Tumor-free animals and animals that had only been subjected to <it>C. albicans </it>infection were used as control groups.</p> <p>Results</p> <p>Our results demonstrated that the mice produced more IFN-γ and TNF-α and less IL-10, and also exhibited fungal clearance, at the beginning of tumor evolution. With the tumor progression, this picture changed: IL-10 production increased and IFN-γ and TNF-α release decreased; furthermore, there was extensive fungal dissemination.</p> <p>Conclusion</p> <p>Our results indicate that solid tumors can affect the production of macrophage cytokines and, in consequence, affect host resistance to opportunistic infections.</p