Health-seeking behavior of Korean women with myocardical infarction

Thesis (Ph.D.)--University of Washington, 2015The purpose of this study was to generate a theory of HSB among Korean women with MI with regard to their experiences of MI at the time of symptom presentation, and the process of treatment seeking. Grounded theory was chosen to explore the experiences of Korean women with MI at the time of symptom presentation to identify Korean women's health-seeking process in getting optimal treatment. Eighteen women participated for 24 interviews using a theoretical sampling from two university hospitals. Twenty-two open-ended interviews were tape-recorded and transcribed verbatim, and then constant comparative analysis was chosen to achieve saturation of theory. The core phenomenon experienced by Korean women was "finding out what's going on and relieving symptoms." The process of HSB for seeking treatment was a sequential and iterative cognitive process. The concepts of health seeking behavior of Korean women with MI were "experiencing symptoms," "attributing symptoms," "evaluating situation," "managing symptoms," "consulting others about symptoms," "getting an optimal treatment," and "maintaining optimal health." Women performed a series of actions through the process from the time of symptoms onset to receiving optimal treatment and maintaining optimal health. For some women, the process was repeated if symptoms evolved and relapse occurred. Inner iteration loops happened among some women as women consulted symptoms to others. Women got alarmed at unusual and evolving symptoms which started from mild and non-specific symptoms ahead of MI. Attributing of symptoms was made based on previous experiences and the evaluating of situations directed the next step on how to relieve symptoms and identify the causes. After an optimal intervention, women paid attention to strategies for maintaining optimal health as an ongoing process. More systematic study of a larger sample size including women in rural areas is needed to compare HSB between two groups, women in rural areas and urban areas as a follow-up study

No Movie to Watch: A Design Strategy for Enhancing Content Diversity through Social Recommendation in the Subscription-Video-On-Demand Service

Increasing diversity is becoming crucial in recommender systems to address the “filter bubble” issue caused by accuracy-based algorithms. Diversity-oriented algorithms have been developed to solve this problem. However, this diversification has made it difficult for users to discover what they really want from the variety of information provided by the algorithm. Users spend their time wandering around the recommended content space but fail to find content they want to watch. Therefore, they rely on external services to gather information that does not appear on the recommended list. This could lead to a reduction in the services’ ability to compete with other subscription video on-demand (SVOD) services. To address this problem, this study proposes a human-centered approach to diversification through social recommendations. We conducted an experiment to understand how perceived diversity affects user perceptions and attitudes. Specifically, by incorporating social recommendations into the SVOD service, this experiment was changed to examine the following conditions: (1) influencers vs. online friends, and (2) human recommendation lists vs. algorithmic recommendation lists. The findings indicated that perceived diversity influences the manner in which the users perceive information quality and playfulness, both of which have a positive effect on their intention to use. Additionally, the participants’ perceptions of information quality were greater in the scenario with the human recommendation than in that with the algorithmic recommendation. This study contributes to the development of a theoretical framework based on perceived diversity through social recommendations and the design of an SVOD interface with social recommendations to provide better user experiences

Activation of Dll4/Notch Signaling and Hypoxia-Inducible Factor-1 Alpha Facilitates Lymphangiogenesis in Lacrimal Glands in Dry Eye.

By using hypoxia-inducible factor-1 alpha conditional knockout (HIF-1α CKO) mice and a dry eye (DE) mouse model, we aimed to determine the role played by delta-like ligand 4 (Dll4)/Notch signaling and HIF-1α in the lymphangiogenesis of lacrimal glands (LGs).C57BL/6 mice were housed in a controlled-environment chamber for DE induction. During DE induction, the expression level of Dll4/Notch signaling and lymphangiogenesis in LGs was measured by quantitative RT-PCR, immunoblot, and immunofluorescence staining. Next, lymphangiogenesis was measured after Dll4/Notch signal inhibition by anti-Dll4 antibody or γ-secretase inhibitor. Using HIF-1α CKO mice, the expression of Dll4/Notch signaling and lymphangiogenesis in LGs of DE-induced HIF-1α CKO mice were assessed. Additionally, the infiltration of CD45+ cells in LGs was assessed by immunohistochemical (IHC) staining and flow cytometry for each condition.DE significantly upregulated Dll4/Notch and lymphangiogenesis in LGs. Inhibition of Dll4/Notch significantly suppressed lymphangiogenesis in LGs. Compared to wild-type (WT) mice, DE induced HIF-1α CKO mice showed markedly low levels of Dll4/Notch and lymphangiogenesis. Inhibition of lymphangiogenesis by Dll4/Notch suppression resulted in increased CD45+ cell infiltration in LGs. Likewise, CD45+ cells infiltrated more in the LGs of HIF-1α CKO DE mice than in non-DE HIF-1α CKO mice.Dll4/Notch signaling and HIF-1α are closely related to lymphangiogenesis in DE-induced LGs. Lymphangiogenesis stimulated by Dll4/Notch and HIF-1α may play a role in protecting LGs from DE-induced inflammation by aiding the clearance of immune cells from LGs

Dry eye stress activates NOTCH1-Dll4 axis and HIF-1α during lymphatic vessel formation of dry eye-induced lacrimal glands.

<p>DE stress activates Dll4/Notch pathway and HIF-1α in LGs. HIF-1α upregulates Dll4/Notch pathway and promotes lymphangiogenesis. Activation of Dll4/Notch pathway and HIF-1α results in increase of VEGF-C, VEGF-D, and VEGFR3, which results in lymphangiogenesis in LGs. (DE = dry eye).</p

Six Germline Genetic Variations Impair the Translesion Synthesis Activity of Human DNA Polymerase kappa

DNA polymerase (pol) κ efficiently catalyzes error-free translesion DNA synthesis (TLS) opposite bulky N2-guanyl lesions induced by carcinogens such as polycyclic aromatic hydrocarbons. We investigated the biochemical effects of nine human nonsynonymous germline POLK variations on the TLS properties of pol κ, utilizing recombinant pol κ (residues 1-526) enzymes and DNA templates containing an N2-CH2(9-anthracenyl)G (N2-AnthG), 8-oxo-7,8-dihydroguanine (8-oxoG), O6-methyl(Me)G, or an abasic site. In steady-state kinetic analyses, the R246X, R298H, T473A, and R512W variants displayed 7- to 18-fold decreases in kcat/Km for dCTP insertion opposite G and N2-AnthG, with 2- to 3-fold decreases in DNA binding affinity, compared to that of the wild-type, and further showed 5- to 190-fold decreases in kcat/Km for next-base extension from C paired with N2-AnthG. The A471V variant showed 2- to 4-fold decreases in kcat/Km for correct nucleotide insertion opposite and beyond G (or N2-AnthG) compared to that of the wild-type. These five hypoactive variants also showed similar patterns of attenuation of TLS activity opposite 8-oxoG, O6-MeG, and abasic lesions. By contrast, the T44M variant exhibited 7- to 11-fold decreases in kcat/Km for dCTP insertion opposite N2-AnthG and O6-MeG (as well as for dATP insertion opposite an abasic site) but not opposite both G and 8-oxoG, nor beyond N2-AnthG, compared to that of the wild-type. These results suggest that the R246X, R298H, T473A, R512W, and A471V variants cause a general catalytic impairment of pol κ opposite G and all four lesions, whereas the T44M variant induces opposite lesion-dependent catalytic impairment, i.e., only opposite O6-MeG, abasic, and bulky N2-G lesions but not opposite G and 8-oxoG, in pol κ, which might indicate that these hypoactive pol κ variants are genetic factors in modifying individual susceptibility to genotoxic carcinogens in certain subsets of populations. © 2016 American Chemical Society.

Change in NOTCH signaling in dry eye-induced lacrimal glands.

<p>After C57BL/6 mice were housed in a CEC with scopolamine administration for 10 days, LGs were obtained and prepared for qRT-PCR, and (A) mRNA levels of NOTCHs, DLLs, and JAGs were measured. (B) The change in the mRNA level of NOTCH1/DLL4 during DE induction was measured (C) During DE induction, each LG samples were prepared for immunoblot for NOTCH1 and DLL4 at Day 2, Day 4, Day 6, Day 8, and Day 10. Densitometry for protein concentreation quantification was done by using ImageJ software. Student’s t-test for statistical analysis: *p<0.05, **p<0.01, †p<0.001. Error bars indicate standard deviation. (CTL = normal control; DE = dry eye).</p

Change in NOTCH signaling and LYVE-1 expression in dry eye-induced HIF-1α conditional knockout mice.

<p>WT B6 and HIF-1α CKO mice were housed in a CEC with scopolamine administration for 10 days. LGs were obtained and prepared for qRT-PCR and (A) The mRNA level of NOTCH1, DLL4, LYVE-1, and Podoplanin at Day 10 was measured. (B) Immunoblot and densitometry for NOTCH1 and LYVE-1 were measured at Day 10. (C) Immunofluorescence staining of LYVE-1 was performed for DE-induced WT B6 mice and DE-induced HIF-1α CKO mice at Day 10. Student’s t-test for statistical analysis: *p<0.05, **p<0.01. Error bars indicate standard deviation. (WT = wild-type; DE = dry eye; HIF-1α CKO = HIF-1α conditional knockout).</p

Change in LYVE-1, VEGF-C, VEGF-D, and VEGFR3 expression after inhibition of the NOTCH1-Dll4 axis by intraperitoneal injection of monoclonal anti-Dll4 antibody and γ-secretase inhibitor.

<p>While C57BL/6 mice were housed in a CEC with scopolamine administration for 10 days, several groups of mice were administered anti-Dll4 Ab and GSI for inhibiting the NOTCH1-DLL4 axis. Anti-IgG Ab was administered as a control for the anti-Dll4 antibody group, and DMSO was administered as a negative control. LGs were obtained after 10 days of DE induction and were prepared for qRT-PCR, immunoblot, and immunostaining. (A) The mRNA levels of LYVE-1, VEGF-C, VEGF-D, and VEGFR3 were measured using qPCR for each group. (B) Immunoblot and densitometry of LYVE-1 were measured for each group. (C) Immunofluorescence staining of LYVE-1 was performed for each group. Student’s t-test for statistical analysis: *p<0.05, **p<0.01. Error bars indicate standard deviation. (CTL = normal control; DE = dry eye; α-Dll4 = anti-Dll4 antibody; α-IgG = anti-IgG antibody; GSI = γ-secretase inhibitor; DMSO = dissolved dimethyl sulfoxide).</p

Change in CD45⁺ cells in dry eye-induced lacrimal glands.

<p>During 10 days of DE induction, (A) LGs were obtained on Days 0, 2, 4, 6, and 10 for IHC staining of CD45⁺ cells. (B) The fold change of CD45⁺ cells was measured at Days 0, 2, 4, 6, and 10. (C) During DE induction, several groups of mice were administered anti-Dll4 Ab and GSI to inhibit the NOTCH1-DLL4 axis. Anti-IgG Ab was administered as a control for the anti-Dll4 Ab group, and DMSO was administered as a negative control. LGs were obtained at Day 10 of DE induction and were prepared for IHC staining of CD45⁺ cells. (D) The actual percentage of CD45⁺ cells was calculated. (E) Flow cytometry for CD45⁺ cells was performed for each condition according to the manufacturer’s protocol. (F) DE was induced for 10 days in B6 and HIF-1CKOmice. LGs were obtained and prepared for IHC staining. (G) The actual percentage of CD45⁺ cells was calculated for non-DE HIF-1α CKO mice and the DE HIF-1α CKO mice. (H) Flow cytometry was performed for the two groups. Student’s t-test for statistical analysis: *p<0.05, **p<0.01, †p<0.001. Error bars indicate standard deviation. (CTL = normal control; DE = dry eye; α-Dll4 = anti-Dll4 antibody; α-IgG = anti-IgG antibody; GSI = γ-secretase inhibitor; DMSO = dissolved dimethyl sulfoxide; HIF-1α CKO = HIF-1α conditional knockout).</p

Change in LYVE-1, PECAM, VEGF-C, VEGF-D, and VEGFR3 expression in dry eye-induced lacrimal glands.

<p>During 10 days of DE induction, LGs were obtained and prepared for qRT-PCR and (A) the mRNA level of LYVE-1 and PECAM was measuredat Day 2, Day 4, Day 6, Day 8, and Day 10 of DE induction. (B) The mRNA levels of VEGF-C, VEGF-D, and VEGFR3 were measured at Day 10. (C) Immunofluorescence staining of LYVE-1 for DE and control group was performed at Day 10. Student’s t-test for statistical analysis: *p<0.05, **p<0.01. Error bars indicate standard deviation. (CTL = normal control; DE = dry eye).</p