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Fibroid explants reveal a higher sensitivity against MDM2 inhibitor nutlin-3 than matching myometrium
Background:
Spontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets. Methods: We have analyzed uterine leiomyomas and matching normal tissue for the expression of p14Arf and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's t test. Results: An in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14Arf in the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of BAX as well as of p21, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers BAX and p21. Because as a rule fibroids express much higher levels of p14Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium. Conclusions: The results show that uterine fibroids represent a cell population of advanced cellular age compared to matching myometrium. Moreover, the data point to members of the p53-network as to potential novel therapeutic targets for the treatment of uterine fibroids.
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Factors associated with treatment of women with osteoporosis or osteopenia from a national survey
Background:
Health outcomes could be improved if women at high risk for osteoporotic fracture were matched to effective treatment. This study determined the extent to which treatment for osteoporosis/osteopenia corresponded to the presence of specific risk factors for osteoporotic fracture.
Methods:
This retrospective analysis of the United States 2007 National Health and Wellness Survey included women age 40+ years who reported having a diagnosis of osteoporosis (69% of 3276) or osteopenia (31% of 3276). Patients were stratified by whether they were or were not taking prescription treatment for osteoporosis/osteopenia. Using 34 patient characteristics as covariates, logistic regression was used to determine factors associated with treatment.
Results:
Current prescription treatment was reported by 1800 of 3276 (54.9%) women with osteoporosis/osteopenia. The following factors were associated with receiving prescription treatment: patient-reported diagnosis of osteoporosis (versus osteopenia); previous bone mineral density test; 2+ fractures since age 50; older age; lower body mass index; better physical functioning; postmenopausal status; family history of osteoporosis; fewer comorbidities; prescription insurance coverage; higher total prescription count; higher ratio of prescription costs to monthly income; higher income; single status; previous visit to a rheumatologist or gynecologist; and 1 or 2 outpatient visits to healthcare provider (vs. none) in the prior 6 months. Glucocorticoid, tobacco, and daily alcohol use were risk factors for fracture that were not associated with treatment.
Conclusions:
There is a mismatch between those women who could benefit from treatment for osteoporosis and those who are actually treated. For example, self-reported use of glucocorticoids, tobacco, and alcohol were not associated with prescription treatment of osteoporosis. Other clinical and socioeconomic factors were associated with treatment (e.g. prescription drug coverage and higher income) or not (e.g. comorbid osteoarthritis and anxiety) and could be opportunities to improve care.
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Traumatic physical health consequences of intimate partner violence against women: what is the role of community-level factors?
Background:
Intimate partner violence (IPV) against women is a serious public health issue with recognizable direct health consequences. This study assessed the association between IPV and traumatic physical health consequences on women in Nigeria, given that communities exert significant influence on the individuals that are embedded within them, with the nature of influence varying between communities.
Methods:
Cross-sectional nationally-representative data of women aged 15 - 49 years in the 2008 Nigeria Demographic and Health Survey was used in this study. Multilevel logistic regression analysis was used to assess the association between IPV and several forms of physical health consequences.
Results:
Bruises were the most common form of traumatic physical health consequences. In the adjusted models, the likelihood of sustaining bruises (OR = 1.91, 95% CI = 1.05 - 3.46), wounds (OR = 2.54, 95% CI = 1.31 - 4.95), and severe burns (OR = 3.20, 95% CI = 1.63 - 6.28) was significantly higher for women exposed to IPV compared to those not exposed to IPV. However, after adjusting for individual- and community-level factors, women with husbands/partners with controlling behavior, those with primary or no education, and those resident in communities with high tolerance for wife beating had a higher likelihood of experiencing IPV, whilst mean community-level education and women 24 years or younger were at lower likelihood of experiencing IPV.
Conclusions:
Evidence from this study shows that exposure to IPV is associated with increased likelihood of traumatic physical consequences for women in Nigeria. Education and justification of wife beating were significant community-level factors associated with traumatic physical consequences, suggesting the importance of increasing women's levels of education and changing community norms that justify controlling behavior and IPV.
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"Its almost expected": rural Australian Aboriginal women's reflections on smoking initiation and maintenance: a qualitative study
Background:
Despite declining smoking rates among the general Australian population, rates among Indigenous Australians remain high, with 47% of the Indigenous population reporting daily smoking - twice that of other Australians. Among women, smoking rates are highest in younger age groups, with more than half of Aboriginal women smoking during pregnancy. A lack of research focused on understanding the social context of smoking by Aboriginal women in rural Australia limits our ability to reduce these rates. This study aimed to explore the factors contributing to smoking initiation among rural Aboriginal women and girls and the social context within which smoking behaviour occurs.
Methods:
We conducted three focus groups with 14 Aboriginal women and service providers and 22 individual interviews with Aboriginal women from four rural communities to explore their perceptions of the factors contributing to smoking initiation among Aboriginal girls.
Results:
Four inter-related factors were considered important to understanding the social context in which girls start smoking: colonisation and the introduction of tobacco; normalization of smoking within separate Aboriginal social networks; disadvantage and stressful lives; and the importance of maintaining relationships within extended family and community networks. Within this context, young girls use smoking to attain status and as a way of asserting Aboriginal identity and group membership, a way of belonging, not of rebelling. Family and social structures were seen as providing strong support, but limited the capacity of parents to influence children not to smoke. Marginalization was perceived to contribute to limited aspirations and opportunities, leading to pleasure-seeking in the present rather than having goals for the future.
Conclusions:
The results support the importance of addressing contextual factors in any strategies aimed at preventing smoking initiation or supporting cessation among Aboriginal girls and women. It is critical to acknowledge Aboriginal identity and culture as a source of empowerment; and to recognise the role of persistent marginalization in contributing to the high prevalence and initiation of smoking.
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Validation of a susceptibility, benefits, and barriers scale for mammography screening among Peruvian women: a cross-sectional study
Background:
Perceived beliefs about breast cancer and breast cancer screening are important predictors for mammography utilization. This study adapted and validated the Champion's scale in Peru. This scale measures perceived susceptibility for breast cancer and perceived benefits and barriers for mammography.
Methods:
A cross-sectional study was conducted among women ages 40 to 65 attending outpatient gynecology services in a public hospital in Peru. A group of experts developed and pre-tested a Spanish version of the Champion's scale to assess its comprehensibility (N = 20). Factor analysis, internal consistency, and test-retest reliability analyses were performed (N = 285). Concurrent validity compared scores from participants who had a mammogram and those who did not have it in the previous 15 months. T-test and multiple regression analysis adjusting for socio-demographic factors, mammography knowledge and other preventive behaviors were performed.
Results:
The construct validity and reliability were optimal. Cronbach-Alpha coefficients were 0.75 (susceptibility), 0.72 (benefits) and 0.86 (barriers). Concurrent validity analysis showed an association between barriers and mammography screening use in bivariate (22.3 ± 6.7 vs. 30.2 ± 7.6; p < 0.001) and multiple regression analysis (OR = 0.28, 95% CI = 0.18-0.43). Ages 50-60 years (OR = 2.35, 95% CI = 1.19-4.65), history of prior Papanicolaou test (OR = 3.69, 95% CI = 1.84-7.40), and knowledge about breast cancer and mammography (OR = 3.69, 95% CI = 1.84-7.40) were also independently associated with mammography screening use.
Conclusion:
Concurrent validity analysis showed that the Champion's scale has important limitations for assessing perceived susceptibility for breast cancer and perceived benefits for mammography among Peruvian women. There is still a need for developing valid and reliable instruments for measuring perceived beliefs about breast cancer and mammography screening among Peruvian women.
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The facilitating factors and barriers encountered in the adoption of a humanized birth care approach in a highly specialized university affiliated hospital
Background:
Considering the fact that a significant proportion of high-risk pregnancies are currently referred to tertiary level hospitals; and that a large proportion of low obstetric risk women still seek care in highly specialized hospitals, it is crucial to explore the factors that influence the childbirth experience in such institutions. The aim of this study was to explore the organizational and cultural factors, which act as barriers or facilitators in the provision of humanized obstetrical care in a highly specialized, university-affiliated hospital, in Montreal, in Canada.MethodA single case study design was chosen. The study sample included 17 professionals and administrators from different disciplines, and 157 women who gave birth in the hospital during the study. The data was collected through semi-structured interviews, field notes, participant observations, a self-administered questionnaire, documents, and archives. Both descriptive and qualitative deductive content analyses were performed, and ethical considerations were respected.
Results:
Both external and internal dimensions of a highly specialized hospital can facilitate or be a barrier to the humanization of birth care practices in such institutions, whether independently, or altogether. The greatest facilitating factors found were caring and family- centered model of care, professionals' ambient for the provision of humanized birth care besides the medical interventions, the care which is tailored to the specific needs of women in order to improve safety, assurance, and comfort for them, facilities to provide a pain-free birth, flexible companionship and visiting rules, deal with the patients' spiritual and religious beliefs. The most cited barriers were the shortage of health care professionals leading lack of choice for women, the lack of sufficient communication among the professionals, the stakeholders' desire for specialization rather than humanization of care, over estimation of medical performance, finally the training environment of the hospital and the presence of too many health care professionals, and consequently, a lack of privacy and continuity of care.
Conclusion:
The argument of medical intervention and technology at birth being an opposing factor to the humanization of birth was not seen to be an issue in the studied highly specialized university affiliated hospital.
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Behind the Silence of Harmony: Risk Factors for Physical and Sexual Violence among Women in Rural Indonesia
Background:
Indonesia has the fourth largest population in the world. Few studies have identified the risk factors of Indonesian women for domestic violence. Such research will be useful for the development of prevention programs aiming at reducing domestic violence. Our study examines associations between physical and sexual violence among rural Javanese Indonesian women and sociodemographic factors, husband's psychosocial and behavioral characteristics and attitudes toward violence and gender roles.
Methods:
A cohort of pregnant women within the Demographic Surveillance Site (DSS) in Purworejo district, Central Java, Indonesia, was enrolled in a longitudinal study between 1996 and 1998. In the following year (1999), a cross-sectional domestic violence household survey was conducted with 765 consenting women from that cohort. Female field workers, trained using the WHO Multi-Country study instrument on domestic violence, conducted interviews. Crude and adjusted odds ratios at 95% CI were applied for analysis.
Results:
Lifetime exposure to sexual and physical violence was 22% and 11%. Sexual violence was associated with husbands' demographic characteristics (less than 35 years and educated less than 9 years) and women's economic independence. Exposure to physical violence among a small group of women (2-6%) was strongly associated with husbands' personal characteristics; being unfaithful, using alcohol, fighting with other men and having witnessed domestic violence as a child. The attitudes and norms expressed by the women confirm that unequal gender relationships are more common among women living in the highlands and being married to poorly educated men. Slightly more than half of the women (59%) considered it justifiable to refuse coercive sex. This attitude was also more common among financially independent women (71%), who also had a higher risk of exposure to sexual violence.
Conclusions:
Women who did not support the right of women to refuse sex were more likely to experience physical violence, while those who justified hitting for some reasons were more likely to experience sexual violence. Our study suggests that Javanese women live in a high degree of gender-based subordination within marriage relationships, maintained and reinforced through physical and sexual violence. Our findings indicate that women's risk of physical and sexual violence is related to traditional gender norms.
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Baropodometry on women suffering from chronic pelvic pain - a cross-sectional study
Background:
Previous studies have associated chronic pelvic pain with a stereotyped pattern of movement and posture, lack of normal body sensations, a characteristic pain distribution. We aimed at evaluating if these postural changes are detectable in baropodometry results in patients with chronic pelvic pain.
Methods:
We performed a prospective study in a university hospital. We selected 32 patients suffering from chronic pelvic pain (study group) and 30 women without this pathology (regular gynecological work out - control group). Pain scores and baropodometric analysis were performed.
Results:
As expected, study group presented higher pain scores than control group. Study and control groups presented similar averages for the maximum pressures to the left and right soles as well as soles supports in the forefeet and hind feet. Women suffering from chronic pelvic pain did not present differences in baropodometric analysis when compared to healthy controls.
Conclusions:
This data demonstrates that postural abnormalities resulting from CPP could not be demonstrated by baropodometric evaluation. Other postural measures should be addressed to evaluate pelvic pain patients.
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Intimate partner violence among women with HIV infection in rural Uganda: critical implications for policy and practice
Background:
Intimate partner violence (IPV) is a major public health problem in Africa and worldwide. HIV infected women face increased IPV risk. We assessed the prevalence and factors associated with IPV among HIV infected women attending HIV care in Kabale hospital, Uganda.
Methods:
This cross-sectional study was conducted among 317 HIV infected women attending Kabale regional hospital HIV treatment centre, from March to December 2010. Participants were interviewed using an interviewer-administered questionnaire. Data was collected on socio-demographic variables, social habits, and IPV (using the abuse assessment screen and the Severity of Violence against Women Scale to identify physical, sexual and psychological violence). Characteristics of the participants who reported IPV were compared with those who did not. Multivariate logistic-regression analysis was conducted to analyze factors that were independently associated with IPV.
Results:
The mean age of 317 respondents was 29.7 years. Twenty two (6.9%) were adolescents and 233 (73.5%) were married or cohabiting. The mean age of the spouse was 33.0 years.One hundred and eleven (35.0%) were currently on antiretroviral therapy. Lifetime prevalence of IPV (physical or sexual) was 36.6%. In the preceding 12 months, IPV (any type) was reported by 93 respondents (29.3%). This was physical for 55 (17.6%), and sexual /psychological for 38 (12.1%). On multivariate multinomial logistic regression analysis, there was a significant but inverse association between education level and physical partner violence (adjusted relative risk (ARR) 0.50, confidence limits (95% CI) 0.31-0.82, p-value = 0.007). There was a significant but inverse association between education level of respondent and sexual/psychological violence (ARR 0.47 95%CI (0.25-0.87), p-value = 0.017) Likewise, there was a significant inverse association between the education level of the spouse and psychological/sexual violence (ARR 0.57, 95% CI 0.25-0.90, p-value = 0.018). Use of antiretroviral therapy was associated with increased prevalence of any type of violence (physical, sexual or psychological) with ARR 3.04 (95%CI 1.15-8.45, p-value = 0.032).
Conclusion:
Almost one in three women living with HIV had suffered intimate partner violence in the preceding 12 months. Nearly one in five HIV patients reported physical violence, and about one in every seven HIV patients reported sexual/psychological violence. Likewise, women who were taking antiretroviral drugs for HIV treatment were more likely to report any type of intimate partner violence (physical, sexual or psychological). The implication of these findings is that women living with HIV especially those on antiretroviral drugs should be routinely screened for intimate partner violence.
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"I am nothing": experiences of loss among women suffering from severe birth injuries in Tanzania
Background:
Despite the increased attention on maternal mortality during recent decades, which has resulted in maternal health being defined as a Millennium Development Goal (MDG), the disability and suffering from obstetric fistula remains a neglected issue in global health. Continuous leaking of urine and the physical, emotional and social suffering associated with it, has a profound impact on women's quality of life. This study seeks to explore the physical, cultural and psychological dimensions of living with obstetric fistula, and demonstrate how these experiences shape the identities of women affected by the condition.
Methods:
A cross-sectional study with qualitative and quantitative components was used to explore the experiences of Tanzanian women living with obstetric fistula and those of their husbands. The study was conducted at the Comprehensive Community Based Rehabilitation Tanzania hospital in Dar es Salaam, Bugando Medical Centre in Mwanza, and Mpwapwa district, in Dodoma region. Conveniently selected samples of 16 women were interviewed, and 151 additional women responded to a questionnaire. In addition, 12 women affected by obstetric fistula and six husbands of these affected women participated in a focus group discussions. Data were analysed using content data analysis framework and statistical package for the social sciences (SPSS) version 15 for Microsoft windows.
Results:
The study revealed a deep sense of loss. Loss of body control, loss of the social roles as women and wives, loss of integration in social life, and loss of dignity and self-worth were located at the core of these experiences.
Conclusion:
The women living with obstetric fistula experience a deep sense of loss that had negative impact on their identity and quality of life. Acknowledging affected women's real-life experiences is important in order to understand the occurrence and management of obstetric fistula, as well as prospects after treatment. This knowledge will help to improve women's sense of self-worth and maintain their identity as women, wives, friends and community members. Educational programmes to empower women socially and economically and counselling of families of women living with obstetric fistula may help these women receive medical and social support that is necessary.
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