25 results on '"Spinler K"'
Search Results
2. Prevalence and determinants of dental visits among older adults: findings of a nationally representative longitudinal study
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Spinler, K., Aarabi, G., Valdez, R., Kofahl, C., Heydecke, G., König, H.-H., and Hajek, A.
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- 2019
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3. Wirkung einer evidenzbasierten digitalen Präventions-App zur Verbesserung der Mundgesundheitskompetenz und Mundgesundheit
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Lieske, B, additional, Aarabi, G, additional, Spinler, K, additional, Dingoyan, D, additional, Poth, A, additional, and Kofahl, C, additional
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- 2022
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4. Oral Health Literacy in Migrant and Ethnic Minority Populations: A Systematic Review
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Valdez, R., primary, Spinler, K., additional, Kofahl, C., additional, Seedorf, U., additional, Heydecke, G., additional, Reissmann, D. R., additional, Lieske, B., additional, Dingoyan, D., additional, and Aarabi, G., additional
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- 2021
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5. Partizipative Entwicklung eines migrationssensiblen, digitalen Schulungsprogramms zur Verbesserung der Mundgesundheitskompetenz von Menschen mit Migrationshintergrund
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Spinler, K, additional, Ungoreit, E, additional, Kofahl, C, additional, Valdez, R, additional, Dingoyan, D, additional, and Aarabi, G, additional
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- 2019
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6. Development of the Oral Health Literacy Profile (OHLP)
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Valdez, R, additional, Spinler, K, additional, Aarabi, G, additional, Reissmann, D, additional, Dingoyan, D, additional, and Kofahl, C, additional
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- 2019
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7. Identification of a Musashi2 translocation as a novel oncogene in myeloid leukemia.
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Spinler K, Hamilton M, Bajaj J, Shima Y, Diaz E, Kritzik M, and Reya T
- Abstract
Myeloid leukemias, diseases marked by aggressiveness and poor outcomes, are frequently triggered by oncogenic translocations. In the case of chronic myelogenous leukemia (CML) the BCR-ABL fusion initiates chronic phase disease with second hits allowing progression to blast crisis. Although Gleevec has been transformative for CML, blast crisis CML remains relatively drug resistant. Here we show that MSI2-HOXA9, a translocation with an unknown role in cancer, can serve as a second hit in driving bcCML. Compared to BCR-ABL, BCR-ABL/MSI2-HOXA9 led to a more aggressive disease in vivo with decreased latency, increased lethality and a differentiation blockade that is a hallmark of blast crisis. Domain mapping revealed that the MSI2 RNA binding domain RRM1 had a preferential impact on growth and lethality of bcCML relative to RRM2 or the HOXA9 domain. Mechanistically, MSI2-HOXA9 triggered global downstream changes with a preferential upregulation of mitochondrial components. Consistent with this, BCR-ABL/MSI2-HOXA9 cells exhibited a significant increase in mitochondrial respiration. These data suggest that MSI2-HOXA9 acts, at least in part, by increasing expression of the mitochondrial polymerase Polrmt and augmenting mitochondrial function and basal respiration in blast crisis. Collectively, our findings demonstrate for the first time that translocations involving the stem and developmental signal MSI2 can be oncogenic, and suggest that MSI, which we found to be a frequent partner for an array of translocations, could also be a driver mutation across solid cancers., Competing Interests: COMPETING INTERESTS T.R. is a founder, and member of the Board of Directors, and holds executive roles at Tiger Hill Therapeutics.
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- 2023
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8. Association between periodontitis and depression severity - A cross-sectional study of the older population in Hamburg.
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Walther C, Lieske B, Borof K, Kühn S, Härter M, Löwe B, Beikler T, Heydecke G, Kuta P, Seedorf U, Spinler K, Gallinat J, and Aarabi G
- Abstract
The aim of the current study is to investigate the association between periodontitis (exposure variable) and depression severity (outcome variable) in an older German population. We evaluated data from 6,209 participants (median age 62 years) of the Hamburg City Health Study (HCHS). The HCHS is a prospective cohort study and is registered at ClinicalTrial.gov (NCT03934957). Depression severity were assessed with the 9-item Patient Health Questionnaire (PHQ-9). Periodontal examination included probing depth, gingival recession, plaque index, and bleeding on probing. Descriptive analyses were stratified by periodontitis severity. Multiple linear regression models were adjusted for age, sex, diabetes, education, smoking, and antidepressant medication. Linear regression analyses revealed a significant association between log-transformed depression severity and periodontitis when including the interaction term for periodontitis * age, even after adjusting for age, sex, diabetes, education, smoking and antidepressant medication. We identified a significant association between severe periodontitis and elevated depression severity, which interacts with age. Additionally, we performed a linear regression model for biomarker analyses, which revealed significant associations between depression severity and severe periodontitis with log-transformed inflammatory biomarkers interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). In order to identify new therapeutic strategies for patients with depression and periodontal disease, future prospective studies are needed to assess the physiological and psychosocial mechanisms behind this relationship and the causal directionality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Inc.)
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- 2023
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9. An Evidence-Based Digital Prevention Program to Improve Oral Health Literacy of People With a Migration Background: Intervention Mapping Approach.
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Weil MT, Spinler K, Lieske B, Dingoyan D, Walther C, Heydecke G, Kofahl C, and Aarabi G
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Background: Studies in Germany have shown that susceptible groups, such as people with a migration background, have poorer oral health than the majority of the population. Limited oral health literacy (OHL) appears to be an important factor that affects the oral health of these groups. To increase OHL and to promote prevention-oriented oral health behavior, we developed an evidence-based prevention program in the form of an app for smartphones or tablets, the Förderung der Mundgesundheitskompetenz und Mundgesundheit von Menschen mit Migrationshintergrund (MuMi) app., Objective: This study aims to describe the development process of the MuMi app., Methods: For the description and analysis of the systematic development process of the MuMi app, we used the intervention mapping approach. The approach was implemented in 6 steps: needs assessment, formulation of intervention goals, selection of evidence-based methods and practical strategies for behavior change, planning and designing the intervention, planning the implementation and delivery of the intervention, and planning the evaluation., Results: On the basis of our literature search, expert interviews, and a focus group with the target population, we identified limited knowledge of behavioral risk factors or proper oral hygiene procedures, limited proficiency of the German language, and differing health care socialization as the main barriers to good oral health. Afterward, we selected modifiable determinants of oral health behavior that were in line with behavior change theories. On this basis, performance objectives and change objectives for the relevant population at risk were formalized. Appropriate behavior change techniques to achieve the program objectives, such as the provision of health information, encouragement of self-control and self-monitoring, and sending reminders, were identified. Subsequently, these were translated into practical strategies, such as multiple-choice quizzes or videos. The resulting program, the MuMi app, is available in the Apple app store and Android app store. The effectiveness of the app was evaluated in the MuMi intervention study. The analyses showed that users of the MuMi app had a substantial increase in their OHL and improved oral hygiene (as measured by clinical parameters) after 6 months compared with the control group., Conclusions: The intervention mapping approach provided a transparent, structured, and evidence-based process for the development of our prevention program. It allowed us to identify the most appropriate and effective techniques to initiate behavior change in the target population. The MuMi app takes into account the cultural and specific determinants of people with a migration background in Germany. To our knowledge, it is the first evidence-based app that addresses OHL among people with a migration background., (©Marie-Theres Weil, Kristin Spinler, Berit Lieske, Demet Dingoyan, Carolin Walther, Guido Heydecke, Christopher Kofahl, Ghazal Aarabi. Originally published in JMIR Formative Research (https://formative.jmir.org), 11.05.2023.)
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- 2023
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10. Correction to: Do postponed dental visits for financial reasons reduce quality of life? Evidence from the Survey of Health, Ageing and Retirement in Europe.
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Valdez R, Aarabi G, Spinler K, Walther C, Kofahl C, Buczak-Stec E, Heydecke G, König HH, and Hajek A
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- 2022
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11. Evidence from the Hamburg City Health Study - association between education and periodontitis.
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Walther C, Spinler K, Borof K, Kofahl C, Heydecke G, Seedorf U, Beikler T, Terschüren C, Hajek A, and Aarabi G
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- Cohort Studies, Educational Status, Humans, Oral Health, Smoking, Periodontitis epidemiology
- Abstract
Objective: Large-scale population-based studies regarding the role of education in periodontitis are lacking. Thus, the aim of the current study was to analyze the potential association between education and periodontitis with state of the art measured clinical phenotypes within a large population-based sample from northern Germany., Material & Methods: The Hamburg City Health Study (HCHS) is a population-based cohort study registered at ClinicalTrial.gov (NCT03934957). Oral health was assessed via plaque-index, probing depth, gingival recession and gingival bleeding. Periodontitis was classified according to Eke & Page. Education level was determined using the International Standard Classification of Education (ISCED-97) further categorized in "low, medium or high" education. Analyses for descriptive models were stratified by periodontitis severity. Ordinal logistic regression models were stepwise constructed to test for hypotheses., Results: Within the first cohort of 10,000 participants, we identified 1,453 with none/mild, 3,580 with moderate, and 1,176 with severe periodontitis. Ordinal regression analyses adjusted for co-variables (age, sex, smoking, diabetes, hypertension and migration) showed that the education level (low vs. high) was significantly associated with periodontitis (OR: 1.33, 95% CI: 1.18;1.47)., Conclusion: In conclusion, the current study revealed a significant association between the education level and periodontitis after adjustments for a set of confounders. Further research is needed to develop strategies to overcome education related deficits in oral and periodontal health., (© 2022. The Author(s).)
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- 2022
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12. The Big Five personality traits and regularity of lifetime dental visit attendance: evidence of the Survey of Health, Ageing, and Retirement in Europe (SHARE).
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Aarabi G, Walther C, Bunte K, Spinler K, Buczak-Stec E, König HH, and Hajek A
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- Aging, Europe, Female, Health Surveys, Humans, Male, Personality, Retirement
- Abstract
Background: Regular dental visits are essential for the prevention, early detection and treatment of worldwide highly prevalent oral diseases. Personality traits were previously associated with treatment compliance, medication adherence and regular doctor visits, however, the link between personality traits and regular dental visit attendance remains largely unexplored. Thus, the objective of this study is to clarify this link., Methods: Data (wave 7) of the Survey of Health, Ageing and Retirement in Europe (SHARE) were used, focusing on Germany (n = 2822). Personality was assessed using the 10-item Big Five Inventory (BFI-10). Regular dental visits were assessed. Multiple logistic regressions were used, adjusting for various covariates., Results: Majority of the participants (84%) reported to attend regular dental visits during lifetime. Regularity of lifetime dental visit attendance was positively and significantly associated with increased extraversion [OR 1.13, 95% CI (1.01-1.26)], increased conscientiousness [OR 1.26, 95% CI (1.10-1.44)], and increased openness to experience [OR 1.12, 95% CI (1.01-1.26)]. However, there was a lack of association with agreeableness and neuroticism. Moreover, the outcome measure was positively associated with younger age, being female, born in Germany, being married, higher education, being retired (compared to being homemaker), whereas it was not associated with obesity or chronic diseases., Conclusions: Identification of personality traits that are associated with regular dental visits can support prevention, screening and clinical management of oral diseases. Further research in this field may facilitate the development and increase the incorporation of individualized concepts to enhance patient compliance and attendance, and thus the provision of oral and dental care services., (© 2021. The Author(s).)
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- 2022
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13. Access Barriers to Dental Treatment and Prevention for Turkish Migrants in Germany - A Qualitative Survey.
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Spinler K, Kofahl C, Ungoreit E, Heydecke G, Dingoyan D, and Aarabi G
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- Dental Care, Germany, Health Services Accessibility, Humans, Language, Transients and Migrants
- Abstract
Introduction: The worldwide migration movement is growing and thereby challenging the health care systems of immigration countries like Germany to make health care equally accessible for all people. Due to their low oral health status and low uptake rates of dental treatment and prevention, migrants were detected as a vulnerable group. Data regarding dental care access barriers of this group is limited. Therefore, the following study established a deeper understanding of unknown access barriers., Methods: Nine expert interviews and one focus group interview were conducted semi-structured via interview guideline in the period of August until October 2018. The experts were persons with strong vocational interactions and experiences with the sector oral health care and migration. The focus group participants had a Turkish migration background., Results: The expert and focus group interviews revealed a variety of barriers that exist toward dental treatment and prevention for migrants. Language, perceived significance of oral health, oral health knowledge, health socialization and patient-dentist interaction were detected to be the main barriers with underlying subthemes and interactions. Furthermore, a predominantly not precaution-oriented dental service utilization of migrants was underlined by the interviewees. Additionally, ways to reach a higher cultural sensitivity in oral health care were stated., Conclusion: With respect for research, there is a need for the integration of migrant-specific items when collecting health data from people. With respect for policy, there is a need for more structural and individual attention for promoting equal access to oral health care and prevention measures for people with a migrant background., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Spinler, Kofahl, Ungoreit, Heydecke, Dingoyan and Aarabi.)
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- 2022
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14. Regular childhood dental visits, health-related factors and quality of life in later life.
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Hajek A, König HH, Buczak-Stec E, Rose LM, Kretzler B, Spinler K, Schiffner U, Aarabi G, and Walther C
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- Aged, Aging, Child, Cross-Sectional Studies, Germany epidemiology, Humans, Quality of Life, Retirement
- Abstract
Purpose To examine the relationship between regular childhood dental visits, and health status and quality of life in later life. Methods Cross-sectional data from wave 7 of the Survey of Health, Ageing and Retirement in Europe (SHARE) were used (n = 2,368; mean age was 66.2 (SD: 9.1, ranging from 50 to 95 years). We focused on data from Germany. Health-related outcome measures (i.e. functional status, cognitive functioning, and self-rated health) were quantified using established tools. Quality of life was assessed using the well-recognized CASP-12. Results In sum, 65.8% of the individuals had regular childhood dental visits. Multiple linear regressions showed that regular childhood dental visits were not associated with present functional status, cognitive functioning or with self-rated health. However, regular childhood dental visits were associated with better quality of life. Moreover, being married, tertiary education (reference: primary education) and not being obese were each associated with higher cognitive functioning, better self-rated health and better quality of life. Conclusion: Regular childhood dental visits were associated with better quality of life. Future studies are required to elucidate the underlying causes., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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15. Development of the Oral Health Literacy Profile (OHLP)-Psychometric properties of the oral health and dental health system knowledge scales.
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Spinler K, Valdez R, Aarabi G, Dingoyan D, Reissmann DR, Heydecke G, von dem Knesebeck O, and Kofahl C
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- Humans, Oral Health, Psychometrics, Reproducibility of Results, Surveys and Questionnaires, Health Literacy
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Objectives: Current oral health literacy (OHL) instruments vary in focus, methodology, administration time and burden. The widely used word recognition tests fail to encompass important OHL domains, while others exceed time frames for use in practical settings, require an interviewer or mainly measure self-assessments. This paper describes the development of the Oral Health Literacy Profile (OHLP), introduces its components and evaluates the psychometric properties of its two core modules, the knowledge tests., Methods: A preliminary version of the questionnaire was developed and assessed for content validity, relevance and redundancy by an expert panel. It was tested in a convenience sample (n = 95) leading to the creation of a 28-item questionnaire, which was afterwards tested in a second convenience sample (n = 193). Item difficulty, discrimination, internal reliability and construct validity were assessed for the oral health knowledge (OHK) and dental health system knowledge (DHSK) modules., Results: The items showed acceptable range of difficulty (ideal: 7 items; easy: 5 items; and difficult: 3 items) and good to very good discriminatory power (the point-biserial index (PBI) > 0.30: all items). Construct validity was considered to be fulfilled when 75% of the hypotheses of expected group differences were met. Satisfactory internal reliability was observed., Conclusion: With all its components, the OHLP is a suitable short instrument to assess the most relevant dimensions of the multifaceted construct of OHL., Practice Implication: The OHLP can be widely used in research, especially suitable in practical settings, and thereby identify patients who may benefit from oral health education., (© 2021 The Authors. Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)
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- 2021
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16. [Oral health literacy of persons with migration background-first results of the MuMi study].
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Spinler K, Weil MT, Valdez R, Walther C, Dingoyan D, Seedorf U, Heydecke G, Lieske B, Kofahl C, and Aarabi G
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- Educational Status, Germany, Health Knowledge, Attitudes, Practice, Humans, Oral Health, Health Literacy, Transients and Migrants
- Abstract
Background: First investigations indicate a migration background of residents in Germany as a discrete risk factor for poor oral health. A lower level of oral health literacy among people with a migration background is considered a reason worthy of being investigated., Aim: This article presents results on oral health literacy and oral health gained from the MuMi study (promoting oral health and oral health literacy of people with a migration background)., Methods: The oral health and oral health literacy as well as the sociodemographics of patients with and without migration background were examined in 40 dental surgeries in Hamburg, Germany. Associations between migrant status, oral health, and oral health literacy were analyzed with logistic regressions. Potential confounders were gradually integrated into the multivariate analyses., Results: Patients with and without a migration background differed significantly in oral health literacy and clinical parameters of oral health (approximal plaque index and degree of caries restoration). The logistic regression analysis revealed highly significant associations between migration background, oral health literacy, and oral hygiene, while also accounting for education and socioeconomic status., Discussion: Migration background constitutes a discrete risk factor for lower oral health and oral health literacy for these relevant population groups. This fact needs stronger reflection in further research and political decision-making in order to promote equality of oral health opportunities., (© 2021. The Author(s).)
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- 2021
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17. Determinants of dental treatment avoidance: findings from a nationally representative study.
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Spinler K, Aarabi G, Walther C, Valdez R, Heydecke G, Buczak-Stec E, König HH, and Hajek A
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- Aged, Cross-Sectional Studies, Dental Care, Female, Germany epidemiology, Humans, Male, Income, Oral Health
- Abstract
Background: Oral health care of older adults is of rising importance due to ongoing demographic changes. There is a lack of studies examining the determinants of dental treatment avoidance in this age group. Therefore, the objective of this study was to identify those determinants., Methods: Cross-sectional data were drawn from the second wave (year 2002) of the German Ageing Survey which is a population-based sample of community-dwelling individuals ≥ 40 years in Germany (n = 3398). Dental treatment avoidance was quantified using the question "Did you need dental treatments in the past twelve months, but did not go to the dentist?" [no; yes, once; yes, several times]. Socioeconomic and health-related determinants were adjusted for in the analysis. Multiple logistic regressions were performed., Results: In terms of need, 6.7% of individuals avoided dental treatment in the preceding twelve months. Multiple logistic regressions revealed that dental treatment avoidance was associated with younger age (total sample [OR 0.978; 95% CI 0.958-0.998] and men [OR 0.970; 95% CI 0.942-0.999]), unemployment (total sample [OR 1.544; 95% CI 1.035-2.302] and men [OR 2.004; 95% CI 1.085-3.702]), lower social strata (women [OR 0.814; 95% CI 0.678-0.977]), increased depressive symptoms (men [OR 1.031; 95% CI 1.001-1.062]), and increased physical illnesses (total sample [OR 1.091; 95% CI 1.006-1.183] and men [OR 1.165; 95% CI 1.048-1.295]). The outcome measure was not associated with income poverty, marital status and physical functioning., Conclusions: The present study highlights the association between dental treatment avoidance and different socioeconomic and health-related factors. These results suggest that it is necessary to promote the importance of dental visits.
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- 2021
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18. Do postponed dental visits for financial reasons reduce quality of life? Evidence from the Survey of Health, Ageing and Retirement in Europe.
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Valdez R, Aarabi G, Spinler K, Walther C, Kofahl C, Buczak-Stec E, Heydecke G, König HH, and Hajek A
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- Aged, Aging, Europe, Female, Germany epidemiology, Humans, Male, Quality of Life, Retirement
- Abstract
Background: There is a lack of studies investigating the impact of postponed dental visits due to financial constraints on quality of life., Aims: The aim of this study was to identify whether these factors are associated longitudinally., Methods: Data were derived from waves 5 and 6 of the "Survey of Health Ageing and Retirement in Europe" (SHARE). The analysis focused on Germany (n = 7506). The widely used CASP-12 was used to quantify the quality of life. Postponed dental visits for financial reasons in the preceding 12 months (no, yes) were used as the main explanatory variable. Socioeconomic and health-related covariates were included in regression analysis., Results: Gender stratified regression analysis showed that quality of life decreased with the presence of postponed dental visits due to financial reasons in men. Furthermore, quality of life decreased with the worsening of self-rated health in both men and women. The outcome measure was not associated with age, marital status, income, and chronic diseases in both sexes., Discussion: Study findings suggest that postponing dental visits due to financial constraints contributes to a decreased quality of life among older men., Conclusion: Efforts to avoid these circumstances might help to maintain the quality of life in older men.
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- 2021
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19. Postponed Dental Appointments Due to Costs Are Associated with Increased Loneliness-Evidence from the Survey of Health, Ageing and Retirement in Europe.
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Walther C, Aarabi G, Valdez R, Spinler K, Heydecke G, Buczak-Stec E, König HH, and Hajek A
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- Aged, Aging, Female, Germany, Humans, Male, Middle Aged, Surveys and Questionnaires, Appointments and Schedules, Dental Health Services economics, Loneliness, Patient Acceptance of Health Care
- Abstract
As is already well known, demographic changes will presumably lead to a rising number of old aged individuals and loneliness is a tremendous concern in aging populations. Poor health can be a potential consequence of loneliness, as well as a determining factor. Thus, the objective of the current study was to determine whether postponed dental appointments due to costs affect loneliness longitudinally. Focusing on Germany, data from two waves (waves 5 and 6) of the "Survey of Health Ageing, and Retirement in Europe" (SHARE) were analyzed ( n = 7703). The three-item loneliness scale (modified version of the revised UCLA Loneliness scale) was used to quantify loneliness. The presence of postponed dental appointments due to costs in the past 12 months (no; yes) served as a key independent variable. Socioeconomic factors as well as health-related factors were adjusted in the longitudinal regression analysis. After adjusting for confounding variables, regression analyses revealed that loneliness increased with decreases in self-rated health among men. Among women, loneliness increased when self-rated health decreased, when fewer chronic diseases and postponed dental appointments due to costs were reported. Among older women, postponed dental appointments due to costs are associated with feelings of loneliness. The study results add evidence that proper dental care (i.e., regular and appropriate visits to the dentist) is vital not only to one's oral health, but also plays a role in one's physical and emotional health.
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- 2021
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20. A stem cell reporter based platform to identify and target drug resistant stem cells in myeloid leukemia.
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Spinler K, Bajaj J, Ito T, Zimdahl B, Hamilton M, Ahmadi A, Koechlein CS, Lytle N, Kwon HY, Anower-E-Khuda F, Sun H, Blevins A, Weeks J, Kritzik M, Karlseder J, Ginsberg MH, Park PW, Esko JD, and Reya T
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- Animals, Antineoplastic Agents therapeutic use, Blast Crisis genetics, Blast Crisis pathology, Chemoradiotherapy methods, Disease Models, Animal, Drug Resistance, Neoplasm drug effects, Gene Knock-In Techniques, Gene Knockout Techniques, Genes, Reporter genetics, Green Fluorescent Proteins chemistry, Green Fluorescent Proteins genetics, High-Throughput Screening Assays, Humans, Imatinib Mesylate pharmacology, Imatinib Mesylate therapeutic use, Integrin beta Chains metabolism, Leukemia, Myeloid, Acute genetics, Leukemia, Myeloid, Acute pathology, Mice, Transgenic, Neoplastic Stem Cells drug effects, Neoplastic Stem Cells radiation effects, RNA-Seq, Signal Transduction drug effects, Syndecan-1 genetics, Syndecan-1 metabolism, Blast Crisis therapy, Leukemia, Myeloid, Acute therapy, Neoplastic Stem Cells pathology, RNA-Binding Proteins genetics, Syndecan-1 antagonists & inhibitors
- Abstract
Intratumoral heterogeneity is a common feature of many myeloid leukemias and a significant reason for treatment failure and relapse. Thus, identifying the cells responsible for residual disease and leukemia re-growth is critical to better understanding how they are regulated. Here, we show that a knock-in reporter mouse for the stem cell gene Musashi 2 (Msi2) allows identification of leukemia stem cells in aggressive myeloid malignancies, and provides a strategy for defining their core dependencies. Specifically, we carry out a high throughput screen using Msi2-reporter blast crisis chronic myeloid leukemia (bcCML) and identify several adhesion molecules that are preferentially expressed in therapy resistant bcCML cells and play a key role in bcCML. In particular, we focus on syndecan-1, whose deletion triggers defects in bcCML growth and propagation and markedly improves survival of transplanted mice. Further, live imaging reveals that the spatiotemporal dynamics of leukemia cells are critically dependent on syndecan signaling, as loss of this signal impairs their localization, migration and dissemination to distant sites. Finally, at a molecular level, syndecan loss directly impairs integrin β
7 function, suggesting that syndecan exerts its influence, at least in part, by coordinating integrin activity in bcCML. These data present a platform for delineating the biological underpinnings of leukemia stem cell function, and highlight the Sdc1-Itgβ7 signaling axis as a key regulatory control point for bcCML growth and dissemination.- Published
- 2020
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21. Association between Subjective Well-Being and Frequent Dental Visits in the German Ageing Survey.
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Valdez R, Aarabi G, Spinler K, Walther C, Seedorf U, Heydecke G, Buczak-Stec E, König HH, and Hajek A
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- Adult, Aged, Female, Humans, Logistic Models, Male, Middle Aged, Self Report, Surveys and Questionnaires, Aging, Dental Care, Personal Satisfaction
- Abstract
The relationship between subjective well-being (SWB) and frequent attendance is understudied. This study used data from a large German sample of non-institutionalized individuals aged 40+ in 2014 ( n = 7264). SWB was measured using the Satisfaction with Life Scale (SWLS) and the Positive and Negative Affect Schedule (PANAS). Number of self-reported dental visits in the past twelve months was used to measure the utilization frequency of dental services. Individuals with at least four dental visits in the preceding year (highest decile) were defined as frequent dental visits. Robustness checks were performed using alternative cut-offs to define frequent dental visits. Multiple logistic regressions showed that frequent dental visits (highest decile) were associated with less satisfaction with life [OR: 0.89, 95%-CI: 0.80-0.99] and higher negative affect [OR: 1.41, 95%-CI: 1.22-1.64], whereas it was not significantly associated with positive affect. Both associations depended on the cut-off chosen to define frequent dental visits. The present study highlights the association between SWB (particularly negative affect and low life satisfaction) and frequent dental visits. Further studies evaluating patients' motivation for high dental service use are necessary to check the robustness of our findings.
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- 2020
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22. An in vivo genome-wide CRISPR screen identifies the RNA-binding protein Staufen2 as a key regulator of myeloid leukemia.
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Bajaj J, Hamilton M, Shima Y, Chambers K, Spinler K, Van Nostrand EL, Yee BA, Blue SM, Chen M, Rizzeri D, Chuah C, Oehler VG, Broome HE, Sasik R, Scott-Browne J, Rao A, Yeo GW, and Reya T
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- Animals, Clustered Regularly Interspaced Short Palindromic Repeats genetics, Genome, Mice, Blast Crisis, Leukemia, Myeloid, Acute genetics, Nerve Tissue Proteins genetics, RNA-Binding Proteins genetics
- Abstract
Aggressive myeloid leukemias such as blast crisis chronic myeloid leukemia and acute myeloid leukemia remain highly lethal. Here we report a genome-wide in vivo CRISPR screen to identify new dependencies in this disease. Among these, RNA-binding proteins (RBPs) in general, and the double-stranded RBP Staufen2 (Stau2) in particular, emerged as critical regulators of myeloid leukemia. In a newly developed knockout mouse, loss of Stau2 led to a profound decrease in leukemia growth and improved survival in mouse models of the disease. Further, Stau2 was required for growth of primary human blast crisis chronic myeloid leukemia and acute myeloid leukemia. Finally, integrated analysis of CRISPR, eCLIP and RNA-sequencing identified Stau2 as a regulator of chromatin-binding factors, driving global alterations in histone methylation. Collectively, these data show that in vivo CRISPR screening is an effective tool for defining new regulators of myeloid leukemia progression and identify the double-stranded RBP Stau2 as a critical dependency of myeloid malignancies., Competing Interests: Competing interests G.W.Y. is co-founder, member of the Board of Directors, on the SAB, equity holder and paid consultant for Locana and Eclipse BioInnovations. G.W.Y. is also a visiting professor at the National University of Singapore and receives travel reimbursement. E.L.V.N. is co-founder, member of the Board of Directors, on the SAB, equity holder and paid consultant for Eclipse BioInnovations. G.W.Y.’s and E.L.V.N.’s interests have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies.
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- 2020
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23. Determinants of Postponed Dental Visits Due to Costs: Evidence from the Survey of Health, Ageing, and Retirement in Germany.
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Aarabi G, Valdez R, Spinler K, Walther C, Seedorf U, Heydecke G, König HH, and Hajek A
- Subjects
- Aged, Aged, 80 and over, Appointments and Schedules, Female, Germany, Humans, Male, Middle Aged, Retirement, Socioeconomic Factors, Surveys and Questionnaires, Dental Health Services economics, Treatment Adherence and Compliance
- Abstract
High costs are an important reason patients postpone dental visits, which can lead to serious medical consequences. However, little is known about the determinants of postponing visits due to financial constraints longitudinally. Thus, the purpose of this study was to examine the determinants of postponing dental visits due to costs in older adults in Germany longitudinally. Data from wave 5 and 6 of the Survey of Health, Ageing, and Retirement in Europe was used. The occurrence of postponed dental visits due to costs in the last 12 months served as the outcome measure. Socioeconomic and health-related explanatory variables were included. Conditional fixed effects logistic regression models were used (n = 362). Regressions showed that the likelihood of postponing dental visits due to costs increased with lower age, less chronic disease, and lower income. The outcome measure was neither associated with marital status nor self-rated health. Identifying the factors associated with postponed dental visits due to costs might help to mitigate this challenge. In the long term, this might help to maintain the well-being of older individuals.
- Published
- 2019
- Full Text
- View/download PDF
24. Cross-linked matrix rigidity and soluble retinoids synergize in nuclear lamina regulation of stem cell differentiation.
- Author
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Ivanovska IL, Swift J, Spinler K, Dingal D, Cho S, and Discher DE
- Subjects
- Animals, Bone and Bones metabolism, Cell Culture Techniques, Cell Differentiation, Cell Movement, Cells, Cultured, Collagen metabolism, Extracellular Matrix physiology, Humans, Induced Pluripotent Stem Cells cytology, Lamin Type A metabolism, Mesenchymal Stem Cells cytology, Nuclear Lamina metabolism, Osteogenesis, Rats, Receptors, Retinoic Acid, Retinoids, Transcription Factors, Extracellular Matrix metabolism, Induced Pluripotent Stem Cells metabolism, Mesenchymal Stem Cells metabolism
- Abstract
Synergistic cues from extracellular matrix and soluble factors are often obscure in differentiation. Here the rigidity of cross-linked collagen synergizes with retinoids in the osteogenesis of human marrow mesenchymal stem cells (MSCs). Collagen nanofilms serve as a model matrix that MSCs can easily deform unless the film is enzymatically cross-linked, which promotes the spreading of cells and the stiffening of nuclei as both actomyosin assembly and nucleoskeletal lamin-A increase. Expression of lamin-A is known to be controlled by retinoic acid receptor (RAR) transcription factors, but soft matrix prevents any response to any retinoids. Rigid matrix is needed to induce rapid nuclear accumulation of the RARG isoform and for RARG-specific antagonist to increase or maintain expression of lamin-A as well as for RARG-agonist to repress expression. A progerin allele of lamin-A is regulated in the same manner in iPSC-derived MSCs. Rigid matrices are further required for eventual expression of osteogenic markers, and RARG-antagonist strongly drives lamin-A-dependent osteogenesis on rigid substrates, with pretreated xenografts calcifying in vivo to a similar extent as native bone. Proteomics-detected targets of mechanosensitive lamin-A and retinoids underscore the convergent synergy of insoluble and soluble cues in differentiation., (© 2017 Ivanovska et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)
- Published
- 2017
- Full Text
- View/download PDF
25. Dynamic domains in polymersomes: mixtures of polyanionic and neutral diblocks respond more rapidly to changes in calcium than to pH.
- Author
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Spinler K, Tian A, Christian DA, Pantano DA, Baumgart T, and Discher DE
- Subjects
- Anions, Edetic Acid chemistry, Calcium chemistry, Hydrogen-Ion Concentration, Polymers chemistry
- Abstract
Chemical triggering of membrane domain dynamics is of broad relevance to cell signaling through lipid bilayers and might also be exploited in application of phase-separated vesicles. Here we describe the morphodynamics and remixing kinetics of spotted polymersomes made with mixtures of polyanionic and neutral amphiphiles plus calcium. Addition of the calcium chelator EDTA to vesicle dispersions produced a decrease in domain size within minutes, whereas increasing the pH with NaOH led to the viscous fingering of domains and decreased domain size over hours. Although the latter suggests that the charge of the polyanion contributes to domain formation, the remixing of more negative chains at high pH is surprising. Domain roughening at high pH is also accelerated by EDTA, which highlights the dominance of cross-bridging. Importantly, even though vesicles were perturbed only externally, the inner and outer leaflets remain coupled throughout, consistent with molecular dynamics simulations and suggestive of an order-disorder transition that underlies the remixing kinetics.
- Published
- 2013
- Full Text
- View/download PDF
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