Using Chinese Version of MYMOP in Chinese Medicine Evaluation: Validity, Responsiveness and Minimally Important Change

<p>Abstract</p> <p>Background</p> <p>Measure Yourself Medical Outcome Profile (MYMOP) is a patient generated outcome instrument applicable in the evaluation of both allopathic and complementary medicine treatment. This study aims to adapt MYMOP into Chinese, and to assess its validity, responsiveness and minimally important change values in a sample of patients using Chinese medicine (CM) services.</p> <p>Methods</p> <p>A Chinese version of MYMOP (CMYMOP) is developed by forward-backward-forward translation strategy, expert panel assessment and pilot testing amongst patients. 272 patients aged 18 or above with subjective symptoms in the past 2 weeks were recruited at a CM clinic, and were invited to complete a set of questionnaire containing CMYMOP and SF-36. Follow ups were performed at 2^ndand 4^thweek after consultation, using the same set of questionnaire plus a global rating of change question. Criterion validity of CMYMOP was assessed by its correlation with SF-36 at baseline, and responsiveness was evaluated by calculating the Cohen effect size (ES) of change at two follow ups. Minimally important difference (MID) values were estimated via anchor based method, while minimally detectable difference (MDC) figures were calculated by distribution based method.</p> <p>Results</p> <p>Criterion validity of CMYMOP was demonstrated by negative correlation between CMYMOP Profile scores and all SF-36 domain and summary scores at baseline. For responsiveness between baseline and 4^thweek follow up, ES of CMYMOP Symptom 1, Activity and Profile reached the moderate change threshold (ES>0.5), while Symptom 2 and Wellbeing reached the weak change threshold (ES>0.2). None of the SF-36 scores reached the moderate change threshold, implying CMYMOP's stronger responsiveness in CM setting. At 2^ndweek follow up, MID values for Symptom 1, Symptom 2, Wellbeing and Profile items were 0.894, 0.580, 0.263 and 0.516 respectively. For Activity item, MDC figure of 0.808 was adopted to estimate MID.</p> <p>Conclusions</p> <p>The findings support the validity and responsiveness of CMYMOP for capturing patient centred clinical changes within 2 weeks in a CM clinical setting. Further researches are warranted (1) to estimate Activity item MID, (2) to assess the test-retest reliability of CMYMOP, and (3) to perform further MID evaluation using multiple, item specific anchor questions.</p

2005 Wild Blueberry Project Reports

The 2005 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Evaluation of Emerging Disinfections Technologies for Wild Blueberry Processing 1A. Incorporation of wild blueberry puree into a soy-based burger and its effect on sensory and chemical properties of the broiled burgers. 2. Incorporation of wild blueberry puree into a soy-based burger and its effect on sensory and chemical properties of the broiled burgers 3. Wild blueberries and Arterial Functional Properties 4. Practical Microbial Control Approach and Antimicrobial Properties Study for Wild Blueberries 5. Wild Blueberries Reduce Risks for Cardiovascular Disease –No Report at this time, data is still under analysis. 6. Irrigation Water Use in Wild Blueberry Production 7. Control Tactics for Blueberry Pest Insects, 2005 8. Integrated Pest Management (IPM) strategies, 2005 9. Control Tactics for Blueberry Pest Insects, 2005 10. The Effect of Fungicides and Cultural Treatments on Monilinia Blight, Yield and Post-Harvest Disease in Wild Blueberries 11. Effect of Soil pH on Nutrient Uptake 12. Effect of Manganese on Growth and Yield of Wild Blueberry 13. Raising Foliar Nitrogen by Application of CoRoN 14. Effects of Summer Foliar Fertilization to Increase Branch Length and Flower Bud Formation in the Prune Year 15. Assessment of Hexazinone Alternatives for Weed Control in Wild Blueberries and Field Cover Program Base 16. Evaluation of Fall Applications of Tribenuron Methyl for Bunchberry Control in Wild Blueberries 17. Evaluation of spot treatments of Tribenuron Methyl for weed control in Wild Blueberries 18. Evaluation and Demonstration of Techniques for Filling in Bare Spots in Wild Blueberry Fields 19. Assessment of Evitol and Kerb for Sedge Control in Wild Blueberrie

2011 Wild Blueberry Project Reports

The 2011 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Mechanisms through which wild blueberries affect functional characteristics of the arterial wall related to endothelial dysfunction in Spontaneously Hypertensive Rats 2. Do wild blueberries affect high blood lipids, high blood glucose and obesity as related to the Metabolic Syndrome? 3. Control tactics for blueberry pest insects, 2011 4. IPM strategies, 2011 5. Biology and ecology of pest insects, 2011 6. Biology and ecology of beneficial insects, 2011 7. Pesticide residues on lowbush blueberry, 2011 8. Maine wild blueberry –mummy berry research and extension 9. Valdensinia leaf spot – Education, control and research – 2011 10. Effect of soil pH on nutrient uptake 11. Evaluation of several growth regulators for stimulating lowbush blueberry rhizome production 12. Evaluation of the effects of Gypsum (CaSO4) on wild blueberry fruit Ca concentration 13. Fall application of tribenuron methyl for bunchberry control in wild blueberries, 2009-2011 – effects of fall versus spring pruning on cover and yield in the crop year (final report) 14. Wild Blueberry Extension Education Program in 2011 INPUT SYSTEMS STUDY: 15. Systems approach to improving the sustainability of wild blueberry production, Year 2 of a four-year study – experimental design 16. The effects of different agronomic practices on the composition and quality of wild blueberries 17. Systems approach to improving the sustainability of wild blueberry production, Year 2 of a four-year study, blueberry quality from the first harvest year 18. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 19. Abundance of insect pest species and natural enemies in lowbush blueberry fields maintained under different management practices 20. Systems approach to improving the sustainability of wild blueberry production, Year 2 of a four-year study, disease management results 21. Systems approach to improving the sustainability of wild blueberry production, Year 2 of a four-year study, weed management results 22. Systems approach to improving sustainability of wild blueberry production, Year 1 of a four-year study, preliminary soil health and chemistry results 23. Management effects on the phosphorus chemistry of wild blueberry barrens soil 24. Systems approach to improving the sustainability of wild blueberry production, preliminary economic comparison 2010-2011 25. Transition to organic production Year 2: Evaluation of gypsum and bone char 26. The effect of field management, forest edge composition, and field location on insect-mediated ecosystem services (scavenging/predation) (ancillary study) 27. Pre-emergent combinations of herbicides for weed control in wild blueberry fields (ancillary study) 28. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, year 1 (ancillary study) 29. Effects of compost and mulch on soil health and soil nutrient dynamics in wild blueberry (ancillary study

2006 Lowbush Blueberry Project Reports

The 2006 edition of the Lowbush Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Evaluation of Emerging Disinfection Technologies for Wild Blueberry Processing 2. Incorporation of wild blueberry puree into a soy-based burger and its effect on sensory and chemical properties of the broiled burgers 3. Infestation Detection using NIRS 4. Mechanism of Action through which Wild Blueberries affect Arterial Functional Properties in Normotensive and Spontaneously Hypertensive Rats 5. Practical Microbial Control Approach for Wild Blueberries and their Antimicrobial Property 6. Wild Blueberry Consumption and Risks for Cardiovascular Disease 7. Irrigation Water use in Wild Blueberry Production 8. Control Tactics for Blueberry Pest Insects & Program Base 9. Integrated Pest Management (IPM) Strategies 10. Biology and Ecology of Blueberry Insect Pests, 2006 11. Research on Wild Blueberry Diseases for 2006-2007 12. Effect of Soil pH on Nutrient Uptake 13. Effect of Manganese on Growth and Yield of Wild Blueberry 14. Effects of Summer Foliar Fertilization to Increase Branch Length and Flower Bud Formation in the Prune Year 15. Effects of Phosphite Foliar Fertilizers on disease control and fruit set of wild blueberry 16. Assessment of Hexazinone Alternatives for Weed Control in Wild Blueberries 17. Evaluation of Fall Applications of Tribenuron Methyl for Bunchberry Control in Wild Blueberries 18. Evaluation of spot treatments of Tribenuron Methyl, Ultim and Roundup for weed control in Wild Blueberries 19. Blueberry Extension Education Program 20. Cultural Weed Management Using p

2012 Wild Blueberry Project Reports

The 2012 edition of the Wild Blueberry Project Reports was prepared for the Wild Blueberry Commission of Maine and the Wild Blueberry Advisory Committee by researchers at the University of Maine, Orono. Projects in this report include: 1. Do wild blueberries alleviate risk factors related to the Metabolic Syndrome? 2. Development of effective intervention measures to maintain and improve food safety for wild blueberries 3. Control tactics for blueberry pest insects, 2012 4. Development and implementation of a wild blueberry thrips IPM program, 2012 5. IPM 6. Biology of blueberry and pest insects, 2012 7. Biology of beneficial insects and blueberry pollination, 2012 8. Pesticide residues on lowbush blueberry, 2012 9. Maine wild blueberry –mummy berry research and extension 10. Efficacy of Apogee growth regulator for stimulating rhizome growth into bare spots in wild blueberry fields 11. Velpar by Matrix pre and post-emergence applications - demonstration plots 12. Wild blueberry Extension Education Program in 2012 INPUT SYSTEMS STUDY: 13. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study – experimental design 14. Food safety- Prevalence study of Escherichia coli O157:H7, Listeria monocytogenes and Salmonella spp. on lowbush blueberries (Vaccinium angustifolium) 15. Abundance of insect pest species and natural enemies in lowbush blueberry fields maintained under different management practices 16. Input Systems Study: Systems approach to improving the sustainability of wild blueberry production, Year 3 of a four-year study, disease management results 17. Plant productivity, Year Three of a four-year study 18. Systems approach to improving the sustainability of wild blueberry production, Year Three of a four-year study, weed management results 19. Effects of organic and conventional management systems on the phosphorus solubility of lowbush blueberry barren soils 20. Systems approach to improving sustainability of wild blueberry production – soil health and chemistry measures 21. Evaluation of fungicides for control of mummy berry disease (ancillary study) 22. Systems approach to improving the sustainability of wild blueberry production – Ancillary land-leveling study, Year Two of a four-year study (ancillary study) 23. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 results from the 2011 trial (ancillary study) 24. Pre-emergent combinations of herbicides for weed control in wild blueberry fields – 2012 trial (ancillary study) 25. Evaluation of herbicides for control of fineleaf sheep fescue for grass control in wild blueberries (ancillary study) 26. Pre-emergence application timing and rate of Alion and Sandea in combination with Velpar or Sinbar on weed control and injury to wild blueberry (ancillary study) 27. Compost and mulch effects on soil health and nutrient dynamics in wild blueberry (ancillary study

Bezielle Selectively Targets Mitochondria of Cancer Cells to Inhibit Glycolysis and OXPHOS

Bezielle (BZL101) is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. Bezielle is an aqueous extract from the herb Scutellaria barbata. We have reported previously that Bezielle was selectively cytotoxic to cancer cells while sparing non-transformed cells. In tumor, but not in non-transformed cells, Bezielle induced generation of ROS and severe DNA damage followed by hyperactivation of PARP, depletion of the cellular ATP and NAD, and inhibition of glycolysis. We show here that tumor cells' mitochondria are the primary source of reactive oxygen species induced by Bezielle. Treatment with Bezielle induces progressively higher levels of mitochondrial superoxide as well as peroxide-type ROS. Inhibition of mitochondrial respiration prevents generation of both types of ROS and protects cells from Bezielle-induced death. In addition to glycolysis, Bezielle inhibits oxidative phosphorylation in tumor cells and depletes mitochondrial reserve capacity depriving cells of the ability to produce ATP. Tumor cells lacking functional mitochondria maintain glycolytic activity in presence of Bezielle thus supporting the hypothesis that mitochondria are the primary target of Bezielle. The metabolic effects of Bezielle towards normal cells are not significant, in agreement with the low levels of oxidative damage that Bezielle inflicts on them. Bezielle is therefore a drug that selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis. This study provides a better understanding of the mechanism of Bezielle's cytotoxicity, and the basis of its selectivity towards cancer cells

Light Chain Separated from the Rest of the Type A Botulinum Neurotoxin Molecule Is the Most Catalytically Active Form

Botulinum neurotoxins (BoNT) are the most potent of all toxins. The 50 kDa N-terminal endopeptidase catalytic light chain (LC) of BoNT is located next to its central, putative translocation domain. After binding to the peripheral neurons, the central domain of BoNT helps the LC translocate into cytosol where its proteolytic action on SNARE (soluble NSF attachment protein receptor) proteins blocks exocytosis of acetyl choline leading to muscle paralysis and eventual death. The translocation domain also contains 105 Å -long stretch of ∼100 residues, known as “belt,” that crosses over and wraps around the LC to shield the active site from solvent. It is not known if the LC gets dissociated from the rest of the molecule in the cytosol before catalysis. To investigate the structural identity of the protease, we prepared four variants of type A BoNT (BoNT/A) LC, and compared their catalytic parameters with those of BoNT/A whole toxin. The four variants were LC + translocation domain, a trypsin-nicked LC + translocation domain, LC + belt, and a free LC. Our results showed that Km for a 17-residue SNAP-25 (synaptosomal associated protein of 25 kDa) peptide for these constructs was not very different, but the turnover number (kcat) for the free LC was 6-100-fold higher than those of its four variants. Moreover, none of the four variants of the LC was prone to autocatalysis. Our results clearly demonstrated that in vitro, the LC minus the rest of the molecule is the most catalytically active form. The results may have implication as to the identity of the active, toxic moiety of BoNT/A in vivo

Control of Centrin Stability by Aurora A

Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer

A Piezoelectric Immunosensor Using Hybrid Self-Assembled Monolayers for Detection of Schistosoma japonicum

BACKGROUND: The parasite Schistosoma japonicum causes schistosomiasis disease, which threatens human life and hampers economic and social development in some Asian countries. An important lesson learned from efforts to reduce the occurrence of schistosomiasis is that the diagnostic approach must be altered as further progress is made towards the control and ultimate elimination of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Using mixed self-assembled monolayer membrane (mixed SAM) technology, a mixture of mercaptopropionic acid (MPA) and mercaptoethanol (ME) was self-assembled on the surface of quartz crystals by gold-sulphur-bonds. Soluble egg antigens (SEA) of S. japonicum were then cross-linked to the quartz crystal using a special coupling agent. As compared with the traditional single self-assembled monolayer immobilization method, S. japonicum antigen (SjAg) immobilization using mixed self-assembled monolayers exhibits much greater immunoreactivity. Under optimal experimental conditions, the detection range is 1:1500 to 1:60 (infected rabbit serum dilution ratios). We measured several infected rabbit serum samples with varying S. japonicum antibody (SjAb) concentrations using both immunosensor and ELISA techniques and then produced a correlation analysis. The correlation coefficients reached 0.973. CONCLUSIONS/SIGNIFICANCE: We have developed a new, simple, sensitive, and reusable piezoelectric immunosensor that directly detects SjAb in the serum. This method may represent an alternative to the current diagnostic methods for S. japonicum infection in the clinical laboratory or for analysis outside the laboratory