Universiẗat, Diss., 2005--Jena.

University, Diss., 2004--Düsseldorf.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

<p>High-throughput processing technologies hold critical position in biomedical research. These include screening of cellular response based on phenotypic difference and production of homogeneous chemicals and biologicals for therapeutic applications. The rapid development of microfluidics technology has provided an efficient, controllable, economical and automatable processing platform for various applications. In particular, emulsion droplet gains a lot of attention due to its uniformity and ease of isolation, but the application of water-in-oil (W/O) single emulsion is hampered by the presence of the oil phase which is incompatible with aqueous phase manipulation and the difficulty in modifying the droplet environment.</p><p>This thesis presents the development of a double emulsion (DE) droplet platform in microfluidics and two applications: (1) high-throughput screening of synthetic gene and (2) production of multicellular spheroids with adjustable microenvironment for controlling stem cell differentiation and liver tissue engineering. Monodisperse DE droplets with controllable size and selective permeability across the oil shell were generated via two microfluidics devices after optimization of device design and flow rates. </p><p>Next, bacterial cells bearing synthetic genes constructed from an inkjet oligonucleotide synthesizer were encapsulated as single cells in DE droplets. Enrichment of fluorescent signals (~100 times) from the cells allowed quantification and selection of functionally-correct genes before and after error correction scheme was employed. Permeation of Isopropyl β-D-1-thiogalactopyranoside (IPTG) molecules from the external phase triggered target gene expression of the pET vector. Fluorescent signals from at least ~100 bacteria per droplet generated clearly distinguishable fluorescent signals that enabled droplets sorting through fluorescence-activated cell sorting (FACS) technique.</p><p>In addition, DE droplets promoted rapid aggregation of mammalian cells into single spheroid in 150 min. Size-tunable human mesenchymal stem cells (hMSC) spheroids could be extracted from the droplets and exhibited better differentiation potential than cells cultured in monolayer. The droplet environment could be altered by loading matrix molecules in it to create spheroid-encapsulated microgel. As an example, hMSC spheroid was encapsulated in alginate or alginate-RGD microgel and enhanced osteogenic differentiation was found in the latter case.</p><p>Lastly, the capability of forming spheroids in DE droplet was applied in liver tissue engineering, where single or co-culture hepatocyte spheroids were efficiently produced and encapsulated in microgel. The use of alginate-collagen microgel significantly improved the long-term function of the spheroid, in a manner similar to forming co-culture spheroids of hepatocytes and endothelial progenitor cells at a 5 to 1 ratio. The hepatocyte spheroid encapsulated in microgel could be useful for developing bioartificial liver or drug testing platform or applied directly for hepatocyte transplantation.</p> / Dissertation

Recent studies have suggested that the diagnostic reliability and accuracy of breast ultrasonography in place of mammography in women with dense breast tissue results in more accurate breast cancer screening in this population. Since breast cancer is the second leading cause of cancer deaths among United States women, a more accurate and reliable breast cancer screening tool is needed (American Cancer Society [ACS], 2014). This process starts with describing breast screening practice patterns of nurse practitioners and analyzing their attitudes and beliefs of alternative screening modalities gathered from the survey results obtained from this DNP project. The purpose of this study is to determine the attitudes and beliefs of if nurse practitioners towards the use of ultrasonography alone in lieu of mammography followed by sonography in women aged 40-74 with mammographically dense breast tissue. A survey consisting of 23 questions was sent to nurse practitioners in Arizona through the Coalition of Arizona Nurses in Advanced Practice listserv, and through an email list provided by the president of the Allied Health Providers of Yuma. Analysis of survey responses indicated that the majority of respondents believe that it is difficult to detect cancer using mammography in women with dense breast tissue, and more than half of respondents believe that ultrasounds are more accurate and reliable at detecting cancer in women with dense breast tissue. The results also demonstrate that the majority of nurse practitioners surveyed are not familiar with current literature regarding ultrasonography screening in women with dense breast tissue.

Jílek L.: The biological activity of secondary plants metabolites II. Alkaloids of Narcissus jonquilla L. Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Botany and Ecology, Hradec Králové 2015, pp. 74. The aim of the diploma thesis was a preparation of alkaloid extracts to identification of alkaloid patterns and measure cholinesterase inhibitory activity. This activity is useful for treating Alzheimer's disease. Alkaloid extracts of seven Narcissus jonquilla L. (Amaryllidaceae) varieties (Bella Estrella, Bell Song, Fruit Cup, Hill Star, Chit Chat, Martinette, Dick Sickel) were studied with respect to their acetylcholinesterase (HuAChE) and butyrylcholinesterase (HuBuChE) inhibitory activity and alkaloid patterns. Thirteen different alkaloids were identified from their mass spectra and retention times. All samples exhibited content of tazettine, most samples contained lycoramine and galanthamine. Promising HuAChE inhibition activity was demonstrated by Narcissus jonquilla L. cv. Bell Song with IC50 values of 6,19 ± 0,85 μg/mL. The strongest inhibitory activity against HuBuChE was detected in extract from Narcissus jonquilla L. cv. Bella Estrella with IC50 value of 18,39 ± 1,51 μg/mL. Keywords: Alzheimer's disease, Amaryllidaceae, Narcissus, GC/MS,...

The high cost and the long time required to bring drugs into commerce is driving efforts to repurpose FDA approved drugs—to find new uses for which they weren’t intended, and to thereby reduce the overall cost of commercialization, and shorten the lag between drug discovery and availability. In comparison to traditional drug repositioning, which relies on serendipitous clinical discoveries, computational methods can systemize the drug search and facilitate the drug development timeline even further. In this dissertation, I report on the development, testing and application of a promising new approach to drug repositioning. This novel computational drug repositioning method is based on mining a human functional linkage network for inversely correlated modules of drug and disease gene targets. Functional linkage network is an evidence-weighted network that provides a quantitative measure of the degree of functional association among any set of human genes. The method takes account of multiple information sources, including gene mutation, gene expression, and functional connectivity and proximity of within module genes. The method was used to identify candidates for treating breast and prostate cancer. We found that (i) the recall rate for FDA approved drugs for breast and (prostate) cancer is 20/20 (10/11), while the rates for drugs in clinical trials were 131/154 and (82/106); (ii) the Area Under the ROC Curve performance substantially exceeds that of two comparable previously published methods; (iii) preliminary in vitro studies indicate that 5/5 identified breast cancer candidates have therapeutic indices superior to that of Doxorubicin in Luminal-A (MCF7) and Triple-Negative (SUM149) breast cancer cell lines. I briefly discuss the biological plausibility of the candidates at a molecular level in the context of the biological processes that they mediate. In conclusion, our method provides a unique way of prioritizing disease causal genes and identifying drug candidates for repositioning, based on innovative computational method. The method appears to offer promise for the identification of multi-targeted drug candidates that can correct aberrant cellular functions. In particular the computational performance exceeded that of existing computational methods. The approach has the potential to provide a more efficient drug discovery pipeline.

Thesis (M.S.H.P.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / The Accountable Care Act (ACA) will expand coverage to millions of Americans. Health insurance plans designed to contain costs and incentivize patients may pose risks that deter members from utilizing recommended services despite provisions such as zero-cost-sharing intended to encourage their use. We evaluated trends (from 2007 to 2011) in health insurance plan type and initial colorectal cancer (CRCA) screening per current guidelines. We hypothesized that consumer-directed and high-deductible health plans (CDHP/HDHP) would be associated with decreased and delayed CRCA screening, and a shift toward lower-cost screening options. Using Thomson MarketScan® data, we analyzed commercial claims for 989,038 American adults (prior colectomy or CRCA excluded) over a full three-year period (starting in January of the fiftieth birthday-year) to assess for CRCA screening (colonoscopy, sigmoidoscopy, or stool test). Using logistic regression, we found that CDHP/HDHP members showed increased likelihood of having had any CRCA screening compared to Preferred Provider Organization (PPO) members, in both Massachusetts (Odds Ratio [OR] 2.321, 95% Confidence Interval [CI] 1.788-3.014) and the Nation (OR 1.640, 95% CI 1.602-1.678). Of those screened, CDHP/HDHP patients were more likely to receive colonoscopy than other recommended alternatives compared to PPO (Massachusetts OR 1.289, 95% CI 1.007-1.651; U.S. OR 1.225, 95% CI 1.192-1.259). Using linear regression, we found that CDHP/HDHP patients were only slightly older at screening compared to PPO, and the difference, while statistically significant, was likely too small to be clinically meaningful. We conclude that contrary to our expectations, CDHP/HDHP members have not been deterred from seeking and obtaining appropriate and timely initial CRCA screening, and they have not chosen lower-cost options. These findings may reflect the newly insured effect, although one limitation of this study was the inability to adjust for selection into CDHP/HDHP. Further study should determine whether CDHP/HDHP members subsequently experience unexpected financial burdens related to CRCA screening that affect future utilization of recommended care. In the pursuit of lower costs through better outcomes, attention should be paid to designing simple and affordable plans with easily understandable features that encourage both patients and providers to follow recommended guidelines while considering the cost-effectiveness of available options. / 2031-01-01

Thesis (M.S.C.E.) PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / BACKGROUND: Patient navigation programs were designed to address barriers to healthcare among underserved populations in order to reduce delays in cancer care delivery. While emerging data suggest modest effects of navigation on reducing delays, there is limited understanding of the association between barriers to care and clinical outcomes within patient navigation programs. OBJECTIVE: To investigate the impact of barriers on timely diagnostic care in the multicenter Patient Navigation Research Program (PNRP). STUDY DESIGN: Secondary analysis of data from the intervention arms of PNRP centers that navigated women for abnormal breast or cervical cancer screening tests from 2007 to 2010. METHODS: Analyses were performed separately for breast and cervical subjects. The main independent variables were (a) number of unique barriers to care (0, 1, 2, or 3+) documented during patient navigation encounters and (b) presence of socio-legal barriers (yes/no), those social problems related to meeting life’s most basic needs that are supported by public policy, regulation, and programming and thus potentially remedied through legal advice or advocacy. The outcome of interest was median time to diagnostic resolution, or the interval from index screening abnormality to diagnostic resolution, estimated using Kaplan-Meier cumulative incidence curves. Multivariable Cox proportional hazards regression with time to diagnostic resolution as the outcome examined the impact of barriers, controlling for socio-demographics and stratifying by study center. RESULTS: Among 2600 breast screening subjects, three-quarters had barriers to care (25% 1 barrier, 16% 2 barriers and 34% 3+ barriers). Among 1387 cervical screening subjects, slightly more than half had barriers (31% 1 barrier, 11% 2 barriers, and 13% 3+ barriers). Among breast subjects, we found the presence of barriers was associated with less timely resolution for any number of barriers compared to no barriers. Among cervical subjects, only the presence of 2 or more barriers was associated with less timely resolution. Both socio-legal and non socio-legal barriers were associated with delay among breast and cervical subjects. CONCLUSIONS: Navigated women with barriers resolve cancer screening abnormalities at a slower rate compared to those with no barriers. Further research is necessary to maximize the impact of patient navigation programs nationwide. / 2031-01-01

BACKGROUND: Cervical cancer has historically been a major cause of mortality for women worldwide. Over the last 50 years, thanks to advances in screening technologies and the implementation of standardized management algorithms, the incidence of cervical cancer in the United States has been declining. LITERATURE REVIEW: In the most recent set of algorithms, the 2012 Updated Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests and Cancer Precursors, the authors conclude that there is high-level evidence to support extended screening intervals for women who are at average-risk for cervical cancer and who have a history of negative screening tests. However, there is large population of women with a history of abnormal screening tests, and their risk of recurrent disease is not well understood. Additionally, the predictive value of the available screening tests for this cohort of women is unknown. The authors of the 2012 Guidelines warn that there is insufficient evidence for optimal management of these women, the current guidelines are based on expert opinion only, and studies providing high-level evidence are lacking. PROPOSED PROJECT: This thesis proposes a systematic literature review of the existing evidence regarding to what extent women who are treated for cervical abnormalities at baseline are at an increased risk for persistent or recurrent disease in the future. Journal articles will be gathered from three different databases and abstracts will be screened for duplicity and relevancy. After article selection, the quality of evidence presented in each paper will be evaluated using the GRADE system to facilitate a methodical and accurate comparison of the existing evidence. Finally, a scheme for data abstraction from the articles will be outlined. CONCLUSIONS: The results of this systematic literature review will serve multiple purposes, including identifying what research has been done since the latest revision of management guidelines, and aiding in the revision of the algorithms for the population of women who have had abnormal screening test results. It will also identify persistent gaps in the body of knowledge regarding this cohort of patients, and guide the development of additional research studies to fill those gaps. SIGNIFICANCE: Determining the risk of recurrent disease in women with abnormal cervical cancer screening tests will serve to more optimally manage this cohort of women. This will allow providers to effectively monitor patients for the recurrence of cervical disease, while also minimizing the risks associated with overscreening.