We investigated how engineered gradients of exogenous growth factors, immobilized to an extracellular matrix material, influence collective guidance of stem cell populations over extended time (>1 day) and length (>1 mm) scales in vitro. Patterns of low-to-high, high-to-low, and uniform concentrations of heparin-binding epidermal growth factor-like growth factor were inkjet printed at precise locations on fibrin substrates. Proliferation and migration responses of mesenchymal stem cells seeded at pattern origins were observed with time-lapse video microscopy and analyzed using both manual and automated computer vision-based cell tracking techniques. Based on results of established chemotaxis studies, we expected that the low-to-high gradient would most effectively direct cell guidance away from the cell source. All printed patterns, however, were found to direct net collective cell guidance with comparable responses. Our analysis revealed that collective "cell diffusion" down a cell-to-cell confinement gradient originating at the cell starting lines and not the net sum of directed individual cell migration up a growth factor concentration gradient is the principal driving force for directing mesenchymal stem cell population outgrowth from a cell source. These results suggest that simple uniform distributions of growth factors immobilized to an extracellular matrix material may be as effective in directing cell migration into a wound site as more complex patterns with concentration gradients.
Eutrophication is the prime water quality issue in inland waters. Eutrophication and its key symptom, harmful cyanobacterial blooms, is expected to further increase in the future, which highlights the importance of managing the issue. The reduction of external nutrient load is crucial but might not bring fast relief to eutrophic waters due to ongoing diffuse pollution and legacy nutrients in the sediment. In this context, in-lake measures are needed to speed-up recovery. In this review, we discuss different in-lake measures based on coagulation and precipitation of cyanobacteria and/or phosphate for different lake categories (e.g., shallow or deep, mainly external or internal nutrient load, occurrence of perennial or summer blooms). In deep lakes with an external nutrient load higher than the internal load, a "Floc and Sink" method could be used in which a coagulant (e.g. aluminium salts, Al-salts; chitosan) combined with a ballast (e.g. soil, clay) removes a cyanobacterial bloom out of the water column. In case the deep lake suffers from high internal load, a phosphate (P)-fixative (e.g. lanthanum modified bentonite or Al-salts) can be used to "Lock" the legacy P, possibly combined with a coagulanta "Floc and Lock" technique. The latter approach will target both the particulate P in a bloom and the internal P load. A shallow lake that suffers from summer blooms and in which the internal load is higher than the external load, a "Lock" strategy of winter application of a P-fixative is proposed to prevent bloom development. In shallow lakes with perennial blooms, an agent to damage the cells (such as H 2 O 2 ) is required together with a coagulant and a ballast to avoid recolonization of the water column due to resuspension -a "Kill, Floc and Sink/ Lock" method. The selection of the most promising in-lake measures and materials should be based on a proper system diagnosis and tests prior to a full-scale intervention. These methods can be effective, but evidently reduction of external nutrient loads, both from point-and non-pointed sources, is an absolute necessity to restore aquatic ecosystems in a holistic sense. recyclable sediment phosphorus (P) pool (Moss, 2010). The most notorious symptom of eutrophication is a massive proliferation of cyanobacteria (Paerl et al., 2011). Blooms of cyanobacteria are viewed problematic as they may produce nasty odours, cause fish kills due to hypoxia/anoxia, and may impair ecosystem services, such as drinking water production, irrigation, recreation, aquaculture and fisheries (Paerl and Paul, 2012). Eutrophication is expected to further increase in the upcoming decades because of human population growth, intensified
Background Azithromycin has been used to treat primary and secondary syphilis and as prophylaxis for sexual partners. We evaluated syphilis treatment failure in patients who received azithromycin therapy. Methods Patients who did not respond to azithromycin therapy were referred to Shanghai Skin Disease and sexually transmitted disease hospital. Treatment failure was defined as follows: (1) persistent ulcers or cutaneous or mucosal lesions 1 month after therapy; or (2) detection of spirochetes in dark-field microscopy examination of a lesion at least 1 week after treatment; or (3) failure of rapid plasma reagin titers to decrease 4-fold at 3 months after treatment. Results A total of 132 patients with primary and secondary syphilis who failed azithromycin therapy were referred to our hospital between January 2001 and October 2008. Of 132 patients, 42 (31.8%) had primary syphilis and 90 (68.2%) had secondary syphilis. Twenty-six patients with primary syphilis developed multiple lesions or secondary syphilis, or persistent ulcers despite using azithromycin. The skin or mucosal lesions did not resolve in 37 patients with secondary syphilis after azithromycin treatment. Ten patients had a positive dark-field examination for Treponema pallidum (T. pallidum) after treatment. The serum rapid plasma reagin titers studied in all cases had failed to decrease 4-fold at 3 months after therapy. The doses of azithromycin used for treatment ranged from 4 to 30 g. Conclusions The failure of azithromycin to cure a substantial number of patients with primary and secondary syphilis in Shanghai suggests that azithromycin has limited therapeutic value in this setting.
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