Cellular uptake, cytotoxicity and DNA-binding studies of the novel imidazoacridinone antineoplastic agent C1311

C1311 is a novel therapeutic agent with potent activity against experimental colorectal cancer that has been selected for entry into clinical trial. The compound has previously been shown to have DNA-binding properties and to inhibit the catalytic activity of topoisomerase II. In this study, cellular uptake and mechanisms by which C1311 interacts with DNA and exerts cytotoxic effects in intact colon carcinoma cells were investigated. The HT29 colon cancer cell line was chosen to follow cellular distribution of C1311 over a time course of 24 h at drug concentrations that just inhibited cell proliferation by 50% or 100%. Nuclear uptake of C1311 and co-localization with lysosomal or mitochondrial dyes was examined by fluorescence microscopy and effects on these cellular compartments were determined by measurement of acid phosphatase levels, rhodamine 123 release or DNA-binding behaviour. The strength and mode of DNA binding was established by thermal melting stabilization, direct titration and viscometric studies of host duplex length. The onset of apoptosis was followed using a TUNEL assay and DNA-fragmentation to determine a causal relationship of cell death. Growth inhibition of HT29 cells by C1311 was concomitant with rapid drug accumulation in nuclei and in this context we showed that the compound binds to duplex DNA by intercalation, with likely A/T sequence-preferential binding. Drug uptake was also seen in lysosomes, leading to lysosomal rupture and a marked increase of acid phosphatase activity 8 h after exposure to C1311 concentrations that effect total growth inhibition. Moreover, at these concentrations lysosomal swelling and breakdown preceded apoptosis, which was not evident up to 24 h after exposure to drug. Thus, the lysosomotropic effect of C1311 appears to be a novel feature of this anticancer agent. As it is unlikely that C1311-induced DNA damage alone would be sufficient for cytotoxic activity, lysosomal rupture may be a critical component for therapeutic efficacy. © 1999 Cancer Research Campaig

The Relative Role of Perceived Partner Risks in Promoting Condom Use in a Three-City Sample of High-Risk, Low-Income Women

We examined the effect of women’s perceptions of sexual partner risks on condom use. Women from three US cities (n = 1,967) were recruited to provide data on HIV risks. In univariate models, increased odds of condom use were associated with perceiving that partners had concurrent partners and being unaware of partners': (a) HIV status, (b) bisexuality, (c) concurrency; and/or (d) injection drug use. In multivariate models, neither being unaware of the four partner risk factors nor perceiving a partner as being high risk was associated with condom use. Contextual factors associated with decreased odds of condom use were having sex with a main partner, homelessness in the past year, alcohol use during sex, and crack use in the past 30 days. Awareness of a partner’s risks may not be sufficient for increasing condom use. Contextual factors, sex with a main partner in particular, decrease condom use despite awareness of partner risk factors

Citizenship beyond politics:the importance of political, civil and social rights and responsibilities among women and men

Previous research has suggested that men are more engaged as citizens than are women.Yet, little is known about gender cleavages across a variety of citizenship norms. To what extent do men and women define citizenship differently? To address that question, this study examines the importance men and women assign various citizenship rights and responsibilities using 2004 ISSP data from 18 Western, industrialized nations. Using a disaggregated approach to understanding definitions of citizenship, we examine political, civil, and social rights and responsibilities. After controlling for a variety of demographic and attitudinal influences, we find that men and women are not different in their views regarding the importance of political responsibilities. However, women do view political rights as significantly more important than do men. Further, in comparison to men, women view both civil and social responsibilities and rights domains as significantly more important

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Image Alive - Using Theatre-Based Techniques to Foster Dialogue About Identity and Oppression

Jodi Beckwith, Co-Founder and Director, Impact Interactive, LLC Jodi Beckwith is an experienced educator, actor, director and facilitator who has been designing and implementing theatre-based training for over 20 years. She has provided professional development, conducted residencies, and trained professionals in education, medicine, and law enforcement. In 1996, Ms. Beckwith created the Education Through Drama Program at Planned Parenthood of Rochester, using interactive drama to help young people problem-solve around health and sexuality issues. She also performs locally in commercials, videos, and on many Rochester stages. She has a BS in human development and family studies from Cornell University, and an MA in educational theatre from NYU. Allison Roberts, Co-Founder and Director, Impact Interactive, LLC Allison Roberts has 15 years of experience working as a trainer, teaching artist, performance educator, and co-facilitator, covering topics such as diversity, sexual harassment, and workplace conflict for both corporate and not-for-profit organizations. She has taught visual arts, improv, acting, and job readiness skills to at-risk youth and students with special needs. She is also an accomplished actor, visual artist and writer. Ms. Roberts performs in local theater productions, short films and commercials, and is the founder, producer and a script-writer for the comedy troupe, EstroFest, which has been running in Rochester for over 15 years.Intersectionality is a complex issue that provokes strong emotions. Through participation in theatre-based activities, participants will learn how interactive theatre can be used to raise awareness, engage diverse perspectives, promote empathy, and foster respectful dialogue about identity and oppression. Participants will reflect on their own thoughts, feelings, and experiences and will leave with a visceral understanding of how these techniques work to create unique opportunities for honest conversation and alliance-building. GOAL/OUTCOME #1 Participants will learn how theatre-based techniques can be used to raise awareness and engage diverse perspectives GOAL/OUTCOME #2 Participants will learn how theatre-based techniques can be used to promote empathy and build alliances between individuals both from and within diverse groups GOAL/OUTCOME #3 Participants will engage in several theatre-based activities and will leave with step-by-step instructions for how to lead them with groups of their ownSUNY BrockportBrockport’s Annual Diversity Conferenc

Image Alive―Using Theatre-Based Techniques to Foster Dialogue About Identity and Oppression

Intersectionality is a complex issue that provokes strong emotions. Through participation in theatre-based activities, participants will learn how interactive theatre can be used to raise awareness, engage diverse perspectives, promote empathy, and foster respectful dialogue about identity and oppression. Participants will reflect on their own thoughts, feelings, and experiences and will leave with a visceral understanding of how these techniques work to create unique opportunities for honest conversation and alliance-building. GOAL/OUTCOME #1 Participants will learn how theatre-based techniques can be used to raise awareness and engage diverse perspectives GOAL/OUTCOME #2 Participants will learn how theatre-based techniques can be used to promote empathy and build alliances between individuals both from and within diverse groups GOAL/OUTCOME #3 Participants will engage in several theatre-based activities and will leave with step-by-step instructions for how to lead them with groups of their ow

Image Alive - Using Theatre-Based Techniques to Foster Dialogue About Diversity and Identity

Jodi Beckwith, Co-Founder and Director, Impact Interactive, LLC Jodi Beckwith is an experienced educator, actor, director and facilitator who has been designing and implementing theatre-based training for over 20 years. She has provided professional development, conducted residencies, and trained professionals in education, medicine, and law enforcement. In 1996, Ms. Beckwith created the Education Through Drama Program at Planned Parenthood of Rochester, using interactive drama to help young people problem-solve around health and sexuality issues. She also performs locally in commercials, videos, and on many Rochester stages. She has a BS in human development and family studies from Cornell University, and an MA in educational theatre from NYU. Allison Roberts, Co-Founder and Director, Impact Interactive, LLC Allison Roberts has 15 years of experience working as a trainer, teaching artist, performance educator, and co-facilitator, covering topics such as diversity, sexual harassment, and workplace conflict for both corporate and not-for-profit organizations. She has taught visual arts, improv, acting, and job readiness skills to at-risk youth and students with special needs. She is also an accomplished actor, visual artist and writer. Ms. Roberts performs in local theater productions, short films and commercials, and is the founder, producer and a script-writer for the comedy troupe, EstroFest, which has been running in Rochester for over 15 years.Intersectionality is a complex issue that provokes strong emotions. Through participation in theatre-based activities, participants will learn how interactive theatre can be used to raise awareness, engage diverse perspectives, promote empathy, and foster respectful dialogue about identity and oppression. Participants will reflect on their own thoughts, feelings, and experiences and will leave with a visceral understanding of how these techniques work to create unique opportunities for honest conversation and alliance-building. GOAL/OUTCOME #1 Participants will learn how theatre-based techniques can be used to raise awareness and engage diverse perspectives GOAL/OUTCOME #2 Participants will learn how theatre-based techniques can be used to promote empathy and build alliances between individuals both from and within diverse groups GOAL/OUTCOME #3 Participants will engage in several theatre-based activities and will leave with step-by-step instructions for how to lead them with groups of their ownSUNY BrockportBrockport’s Annual Diversity Conferenc