1,115 research outputs found
A compilation of arithmetic teaching aids for the kindergarten
Thesis (Ed.M.)--Boston Universit
Comprehension following silent and oral reading in grades two and three
Thesis (Ed.M.)--Boston Universit
Comprehension following silent and oral reading in grades two and three
Thesis (Ed.M.)--Boston Universit
Novel Topical Microbicides Through Combinatorial Strategies
Purpose Developing microbicides for topical epithelial applications is extremely challenging, as evidenced by the scarcity of approved products even after decades of research. Chemical enhancers, including surfactants, are known to be effective antimicrobial agents but are typically toxic towards epithelial cells. Here, we report on the discovery of unique surfactant formulations with improved safety and efficacy profile for epithelial applications, via a combination of high throughput screening techniques. Methods Over three-hundred formulations derived from nine surfactants were screened for antibacterial properties against E. coli in vitro. A subset of these formulations showed high antibacterial activity and was screened for cytotoxicity in vitro. Formulations showing high antibacterial activity and reduced cytotoxicity compared to their individual components were tested for efficacy against B. thailendensis, a model for melioidosis-causing B. pseudomallei. Results Lead formulations showed lower toxicity towards epidermal keratinocytes, with LC50 values up to 3.5-fold higher than their component surfactants, while maintaining antibacterial efficacy against B. thailendensis. Conclusions Our results demonstrate that such a combinatorial screening approach can be used for designing safe and potent microbicides for epithelial applications
Influence of energy balance on the antimicrobial peptides S100A8 and S100A9 in the endometrium of the postpartum dairy cow
Uterine inflammation occurs after calving in association with extensive endometrial remodelling and bacterial contamination. If the inflammation persists, it leads to reduced fertility. Chronic endometritis is highly prevalent in high-yielding cows that experience negative energy balance (NEB) in early lactation. This study investigated the effect of NEB on the antimicrobial peptides S100A8 and S100A9 in involuting uteri collected 2 weeks post partum. Holstein-Friesian cows (six per treatment) were randomly allocated to two interventions designed to produce mild or severe NEB (MNEB and SNEB) status. Endometrial samples were examined histologically, and the presence of neutrophils, macrophages, lymphocytes and natural killer cells was confirmed using haematoxylin and eosin and immunostaining. SNEB cows had greater signs of uterine inflammation. Samples of previously gravid uterine horn were used to localise S100A8 and S100A9 by immunohistochemistry. Both S100 proteins were present in bovine endometrium with strong staining in epithelial and stromal cells and in infiltrated leucocytes. Immunostaining was significantly higher in SNEB cows along with increased numbers of segmented neutrophils. These results suggest that the metabolic changes of a post-partum cow suffering from NEB delay uterine involution and promote a chronic state of inflammation. We show that upregulation of S100A8 and S100A9 is clearly a key component of the early endometrial response to uterine infection. Further studies are warranted to link the extent of this response after calving to the likelihood of cows developing endometritis and to their subsequent fertility
Evidence that vitamin D3 promotes mast cell–dependent reduction of chronic UVB-induced skin pathology in mice
Mast cell production of interleukin-10 (IL-10) can limit the skin pathology induced by chronic low-dose ultraviolet (UV)-B irradiation. Although the mechanism that promotes mast cell IL-10 production in this setting is unknown, exposure of the skin to UVB irradiation induces increased production of the immune modifying agent 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3). We now show that 1α,25(OH)2D3 can up-regulate IL-10 mRNA expression and induce IL-10 secretion in mouse mast cells in vitro. To investigate the roles of 1α,25(OH)2D3 and mast cell vitamin D receptor (VDR) expression in chronically UVB-irradiated skin in vivo, we engrafted the skin of genetically mast cell–deficient WBB6F1-KitW/W-v mice with bone marrow–derived cultured mast cells derived from C57BL/6 wild-type or VDR−/− mice. Optimal mast cell–dependent suppression of the inflammation, local production of proinflammatory cytokines, epidermal hyperplasia, and epidermal ulceration associated with chronic UVB irradiation of the skin in KitW/W-v mice required expression of VDR by the adoptively transferred mast cells. Our findings suggest that 1α,25(OH)2D3/VDR-dependent induction of IL-10 production by cutaneous mast cells can contribute to the mast cell’s ability to suppress inflammation and skin pathology at sites of chronic UVB irradiation
Ultraviolet Irradiation Induces the Accumulation of Chondroitin Sulfate, but Not Other Glycosaminoglycans, in Human Skin
Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV
How to train surgical residents to perform laparoscopic roux-en-Y gastric bypass safely
Background As a result of increasing numbers of patients with morbid obesity there is a worldwide demand for bariatric surgeons. The Roux-en-Y gastric bypass, nowadays performed mostly laparoscopically (LRYGB), has been proven to be a highly effective surgical treatment for morbid obesity. This procedure is technically demanding and requires a long learning curve. Little is known about implementing these demanding techniques in the training of the surgical resident. The aim of this study was to evaluate the safety and feasibility of the introduction of LRYGB into the training of surgical residents. Methods All patients who underwent LRYGB between March 2006 and July 2010 were retrospectively analyzed. The procedure was performed by a surgical resident under strict supervision of a bariatric surgeon (group I) or by a bariatric surgeon (group II). The primary end point was the occurrence of complications. Secondary end points included operative time, days of hospitalization, rate of readmission, and reappearance in the emergency department (ED) within 30 days. Results A total of 409 patients were found eligible for inclusion in the study: 83 patients in group I and 326 in group II. There was a significant difference in operating time (129 min in group I vs. 116 min in group II; p<0.001) and days of hospitalization. Postoperative complication rate, reappearance in the ED, and rate of readmission did not differ between the two groups. Conclusions Our data suggest that under stringent supervision and with sufficient laparoscopic practice, implementation of LRYGB as part of surgical training is safe and results in only a slightly longer operating time. Complication rates, days of hospitalization, and the rates of readmission and reappearance in the ED within 30 days were similar between the both groups. These results should be interpreted by remembering that all procedures in group I were performed in a training environment so occasional intervention by a bariatric surgeon, when necessary, was inevitable
Constitutive modelling of skin ageing
The objective of this chapter is to review the main biomechanical and structural aspects associated with both intrinsic and extrinsic skin ageing, and to present potential research avenues to account for these effects in mathematical and computational models of the skin. This will be illustrated through recent work of the authors which provides a basis to those interested in developing mechanistic constitutive models capturing the mechanobiology of skin across the life course
Digital Well-Being and Manipulation Online
Social media use is soaring globally. Existing research of its ethical implications predominantly focuses on the relationships amongst human users online, and their effects. The nature of the software-to-human relationship and its impact on digital well-being, however, has not been sufficiently addressed yet. This paper aims to close the gap. I argue that some intelligent software agents, such as newsfeed curator algorithms in social media, manipulate human users because they do not intend their means of influence to reveal the user’s reasons. I support this claim by defending a novel account of manipulation and by showing that some intelligent software agents are manipulative in this sense. Apart from revealing a priori reason for thinking that some intelligent software agents are manipulative, the paper offers a framework for further empirical investigation of manipulation online
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