Inhibition of \u3cem\u3eRhizobium etli\u3c/em\u3e Polysaccharide Mutants by \u3cem\u3ePhaseolus vulgaris\u3c/em\u3e Root Compounds

Crude bean root extracts of Phaseolus vulgaris were tested for inhibition of the growth of several polysaccharide mutants of Rhizobium etli biovar phaseoli CE3. Mutants deficient only in exopolysaccharide and some mutants deficient only in the O-antigen of the lipopolysaccharide were no more sensitive than the wild-type strain to the extracts, whereas mutants defective in both lipopolysaccharide and exopolysaccharide were much more sensitive. The inhibitory activity was found at much higher levels in roots and nodules than in stems or leaves. Inoculation with either wild-type or polysaccharide-deficient R. etli did not appear to affect the level of activity. Sequential extractions of the crude root material with petroleum ether, ethyl acetate, methanol, and water partitioned inhibitory activity into each solvent except methanol. The major inhibitors in the petroleum ether and ethyl acetate extracts were purified by C18 high-performance liquid chromatography. These compounds all migrated very similarly in both liquid and thin-layer chromatography but were distinguished by their mass spectra. Absorbance spectra and fluorescence properties suggested that they were coumestans, one of which had the mass spectrum and nuclear magnetic resonances of coumestrol. These results are discussed with regard to the hypothesis that one role of rhizobial polysaccharides is to protect against plant toxins encountered during nodule development

Likely Geographic Distributional Shifts among Medically Important Tick Species and Tick-Associated Diseases under Climate Change in North America: A Review

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Ticks rank high among arthropod vectors in terms of numbers of infectious agents that they transmit to humans, including Lyme disease, Rocky Mountain spotted fever, Colorado tick fever, human monocytic ehrlichiosis, tularemia, and human granulocytic anaplasmosis. Increasing temperature is suspected to affect tick biting rates and pathogen developmental rates, thereby potentially increasing risk for disease incidence. Tick distributions respond to climate change, but how their geographic ranges will shift in future decades and how those shifts may translate into changes in disease incidence remain unclear. In this study, we have assembled correlative ecological niche models for eight tick species of medical or veterinary importance in North America (Ixodes scapularis, I. pacificus, I. cookei, Dermacentor variabilis, D. andersoni, Amblyomma americanum, A. maculatum, and Rhipicephalus sanguineus), assessing the distributional potential of each under both present and future climatic conditions. Our goal was to assess whether and how species’ distributions will likely shift in coming decades in response to climate change. We interpret these patterns in terms of likely implications for tick-associated diseases in North America

Skeletal muscle contractile function in heart failure with reduced ejection fraction - A focus on nitric oxide

Despite advances over the past few decades, heart failure with reduced ejection fraction (HFrEF) remains not only a mortal but a disabling disease. Indeed, the New York Heart Association classification of HFrEF severity is based on how much exercise a patient can perform. Moreover, exercise capacity-both aerobic exercise performance and muscle power-are intimately linked with survival in patients with HFrEF. This review will highlight the pathologic changes in skeletal muscle in HFrEF that are related to impaired exercise performance. Next, it will discuss the key role that impaired nitric oxide (NO) bioavailability plays in HFrEF skeletal muscle pathology. Lastly, it will discuss intriguing new data suggesting that the inorganic nitrate \u27enterosalivary pathway\u27 may be leveraged to increase NO bioavailability via ingestion of inorganic nitrate. This ingestion of inorganic nitrate has several advantages over organic nitrate (e.g., nitroglycerin) and the endogenous nitric oxide synthase pathway. Moreover, inorganic nitrate has been shown to improve exercise performance: both muscle power and aerobic capacity, in some recent small but well-controlled, cross-over studies in patients with HFrEF. Given the critical importance of better exercise performance for the amelioration of disability as well as its links with improved outcomes in patients with HFrEF, further studies of inorganic nitrate as a potential novel treatment is critical

Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor.

BackgroundGastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease.MethodsFresh tumor tissue from three patients with pathologically confirmed GISTs was obtained immediately following tumor resection. Tumor fragments (4.2-mm3) were surgically xenografted into the liver, gastric wall, renal capsule, and pancreas of immunodeficient mice. Tumor growth was serially assessed with ultrasonography (US) every 3-4 weeks. Tumors were also evaluated with positron emission tomography (PET). Animals were sacrificed when they became moribund or their tumors reached a threshold size of 2500-mm3. Tumors were subsequently passaged, as well as immunohistochemically and histologically analyzed.ResultsHerein, we describe the first model for generating orthotopic GIST PDXs. We have successfully xenografted three unique KIT-mutated tumors into a total of 25 mice with an overall success rate of 84% (21/25). We serially followed tumor growth with US to describe the natural history of PDX growth. Successful PDXs resulted in 12 primary xenografts in NOD-scid gamma or NOD-scid mice while subsequent successful passages resulted in 9 tumors. At a median of 7.9 weeks (range 2.9-33.1 weeks), tumor size averaged 473 ± 695-mm³ (median 199-mm3, range 12.6-2682.5-mm³) by US. Furthermore, tumor size on US within 14 days of death correlated with gross tumor size on necropsy. We also demonstrated that these tumors are FDG-avid on PET imaging, while immunohistochemically and histologically the PDXs resembled the primary tumors.ConclusionsWe report the first orthotopic model of human GIST using patient-derived tumor tissue. This novel, reproducible in vivo model of human GIST may enhance the study of GIST biology, biomarkers, personalized cancer treatments, and provide a preclinical platform to evaluate new therapeutic agents for GIST

Community perceptions and factors influencing utilization of health services in Uganda

<p>Abstract</p> <p>Background</p> <p>Healthcare utilization has particular relevance as a public health and development issue. Unlike material and human capital, there is little empirical evidence on the utility of social resources in overcoming barriers to healthcare utilization in a developing country context. We sought to assess the relevance of social resources in overcoming barriers to healthcare utilization.</p> <p>Study Objective</p> <p>To explore community perceptions among three different wealth categories on factors influencing healthcare utilization in Eastern Uganda.</p> <p>Methods</p> <p>We used a qualitative study design using Focus Group Discussions (FGD) to conduct the study. Community meetings were initially held to identify FGD participants in the different wealth categories, ('least poor', 'medium' and 'poorest') using poverty ranking based on ownership of assets and income sources. Nine FGDs from three homogenous wealth categories were conducted. Data from the FGDs was analyzed using content analysis revealing common barriers as well as facilitating factors for healthcare service utilization by wealth categories. The Health Access Livelihood Framework was used to examine and interpret the findings.</p> <p>Results</p> <p>Barriers to healthcare utilization exist for all the wealth categories along three different axes including: the health seeking process; health services delivery; and the ownership of livelihood assets. Income source, transport ownership, and health literacy were reported as centrally useful in overcoming some barriers to healthcare utilization for the 'least poor' and 'poor' wealth categories. The 'poorest' wealth category was keen to utilize free public health services. Conversely, there are perceptions that public health facilities were perceived to offer low quality care with chronic gaps such as shortages of essential supplies. In addition to individual material resources and the availability of free public healthcare services, social resources are perceived as important in overcoming utilization barriers. However, there are indications that having access to social resources may compensate for the lack of material resources in relation to use of health care services mainly for the least poor wealth category.</p> <p>Conclusion</p> <p>The differential patterning of social resources may explain or contribute to the persisting inequities in health care utilization. Additional research using quantitative analytical methods is needed to test the robustness of the contribution of social resources to the utilization of and access to healthcare services.</p