6,469 research outputs found

    Sodium arsenite and hyperthermia modulate cisplatin-DNA damage responses and enhance platinum accumulation in murine metastatic ovarian cancer xenograft after hyperthermic intraperitoneal chemotherapy (HIPEC)

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    <p>Abstract</p> <p>Background</p> <p>Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer death in the USA. Recurrence rates are high after front-line therapy and most patients eventually die from platinum (Pt) - resistant disease. Cisplatin resistance is associated with increased nucleotide excision repair (NER), decreased mismatch repair (MMR) and decreased platinum uptake. The objective of this study is to investigate how a novel combination of sodium arsenite (NaAsO<sub>2</sub>) and hyperthermia (43°C) affect mechanisms of cisplatin resistance in ovarian cancer.</p> <p>Methods</p> <p>We established a murine model of metastatic EOC by intraperitoneal injection of A2780/CP70 human ovarian cancer cells into nude mice. We developed a murine hyperthermic intraperitoneal chemotherapy model to treat the mice. Mice with peritoneal metastasis were perfused for 1 h with 3 mg/kg cisplatin ± 26 mg/kg NaAsO<sub>2 </sub>at 37 or 43°C. Tumors and tissues were collected at 0 and 24 h after treatment.</p> <p>Results</p> <p>Western blot analysis of p53 and key NER proteins (ERCC1, XPC and XPA) and MMR protein (MSH2) suggested that cisplatin induced p53, XPC and XPA and suppressed MSH2 consistent with resistant phenotype. Hyperthermia suppressed cisplatin-induced XPC and prevented the induction of XPA by cisplatin, but it had no effect on Pt uptake or retention in tumors. NaAsO<sub>2 </sub>prevented XPC induction by cisplatin; it maintained higher levels of MSH2 in tumors and enhanced initial accumulation of Pt in tumors. Combined NaAsO<sub>2 </sub>and hyperthermia decreased cisplatin-induced XPC 24 h after perfusion, maintained higher levels of MSH2 in tumors and significantly increased initial accumulation of Pt in tumors. ERCC1 levels were generally low except for NaAsO<sub>2 </sub>co-treatment with cisplatin. Systemic Pt and arsenic accumulation for all treatment conditions were in the order: kidney > liver = spleen > heart > brain and liver > kidney = spleen > heart > brain respectively. Metal levels generally decreased in systemic tissues within 24 h after treatment.</p> <p>Conclusion</p> <p>NaAsO<sub>2 </sub>and/or hyperthermia have the potential to sensitize tumors to cisplatin by inhibiting NER, maintaining functional MMR and enhancing tumor platinum uptake.</p

    The 68th Tank Battalion in combat

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    This will be the record of the 68th Tank Battalion\u27s participation in successive campaigns from the historic breakthrough in Normandy to VE Day in the heart of Germany. Before beginning this narrative, however, there are some remarks we must make. Firstly, this history was made possible by the heroically spent blood and sweat of American men, who gave their best for their country. They did well, these men, and though some of them are no longer with us, their deeds will never be forgotten.https://digicom.bpl.lib.me.us/ww_reg_his/1003/thumbnail.jp

    Generalized Phase Space Representation of Operators

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    Introducing asymmetry into the Weyl representation of operators leads to a variety of phase space representations and new symbols. Specific generalizations of the Husimi and the Glauber-Sudarshan symbols are explicitly derivedComment: latex, 8 pages, expanded version accepted by J. Phys.

    Demographic, socioeconomic, and health correlates of unmet need for mental health treatment in the United States, 2002–16: evidence from the national surveys on drug use and health

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    Abstract: Background: Unmet need for mental health services remains high in the United States and is disproportionately concentrated in some groups. The scale and nature of these disparities have not been fully elucidated and bear further scrutiny. As such, in this study, we examine the demographic, socioeconomic, and health correlates of unmet need for mental health treatment as well as the reasons for unmet need. Methods: We draw upon the National Survey for Drug Use and Health (NSDUH) from 2002 to 16 for adults aged 18 and over in the United States (n = 579,017). Using multivariable logistic regression, we simultaneously model the demographic, socioeconomic, and health correlates of unmet need for mental health treatment from 2002 to 16. We also analyse the reasons for unmet need expressed by these populations, reasons which include cost, perceived stigma, minimisation of symptoms, low perceived effectiveness of treatment, and structural barriers. Results: Major characteristics associated with increased odds of unmet need include past year substance abuse or dependence (other than hallucinogens and sedatives), fair, poor, or very poor health, being female, and an educational attainment of college or higher. With respect to reasons for unmet need, cost was most often cited, followed by perceived stigma, structural barriers, and minimisation. Characteristics associated with increased odds of indicating cost as a reason for unmet need include: being uninsured or aged 26–35. Minimisation and low perceived effectiveness are mentioned by high-income persons as reasons for unmet need. College-educated persons and women had higher odds of citing structural barriers as a reason for unmet need. Conclusions: The correlates and causes of unmet need highlight the intersectionality of individual health needs with implications on addressing inequities in mental health policy and practice

    Validity of the new lifestyles NL-1000 accelerometer for measuring time spent in moderate-to-vigorous physical activity in school settings

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    Current interest in promoting physical activity in the school environment necessitates an inexpensive, accurate method of measuring physical activity in such settings. Additionally, it is recognized that physical activity must be of at least moderate intensity in order to yield substantial health benefits. The purpose of the study, therefore, was to determine the validity of the New Lifestyles NL-1000 (New Lifestyles, Inc., Lee's Summit, Missouri, USA) accelerometer for measuring moderate-to-vigorous physical activity in school settings, using the Actigraph GT1M (ActiGraph, Pensacola, Florida, USA) as the criterion. Data were collected during a cross-country run (n = 12), physical education (n = 18), and classroom-based physical activities (n = 42). Significant and meaningful intraclass correlations between methods were found, and NL-1000 estimates of moderate-to-vigorous physical activity were not meaningfully different from GT1M-estimated moderate- to-vigorous physical activity. The NL-1000 therefore shows promising validity evidence as an inexpensive, convenient method of measuring moderate-to-vigorous physical activity in school settings

    Slogging and Stumbling Toward Social Justice in a Private Elementary School: The Complicated Case of St. Malachy

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    This case study examines St. Malachy, an urban Catholic elementary school primarily serving children traditionally marginalized by race, class, linguistic heritage, and disability. As a private school, St. Malachy serves the public good by recruiting and retaining such traditionally marginalized students. As empirical studies involving Catholic schools frequently juxtapose them with public schools, the author presents this examination from a different tack. Neither vilifying nor glorifying Catholic schooling, this study critically examines the pursuit of social justice in this school context. Data gathered through a 1-year study show that formal and informal leaders in St. Malachy adapted their governance, aggressively sought community resources, and focused their professional development to build the capacity to serve their increasingly pluralistic student population. The analysis confirms the deepening realization that striving toward social justice is a messy, contradictory, and complicated pursuit, and that schools in both public and private sectors are allies in this pursuit

    A comparison of the prevalence of health problems among adults with and without intellectual disability:A total administrative population study

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    Introduction There is considerable international research indicating health disparities between people with and without intellectual disabilities. It is important that comparative studies use representative population samples. This study compares a total administrative population of adults with intellectual disability to a random stratified general population sample. Methods An administrative population of 217 adults with intellectual disability and a random stratified sample of 2,350 adults without intellectual disability participated. A questionnaire using the International Classification of Diseases (ICD‐10) Chapter Headings was administered to all participants to enable a like‐for‐like comparison. Findings Unadjusted comparisons identified that adults with intellectual disability have a greater prevalence of health problems. These problems start early in adulthood and continue throughout life. However, they were less likely to experience cancers and musculoskeletal diseases. Conclusions These findings are consistent with the hypothesis that adults with intellectual disabilities have greater prevalence rates of health problems than the general population

    Bures and Statistical Distance for Squeezed Thermal States

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    We compute the Bures distance between two thermal squeezed states and deduce the Statistical Distance metric. By computing the curvature of this metric we can identify regions of parameter space most sensitive to changes in these parameters and thus lead to optimum detection statistics.Comment: 15 pages, 1 figure (not included - obtain from Author) To appear in Journal of Physics
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