Reactive Oxygen Species via Redox Signaling to PI3K/AKT Pathway Contribute to the Malignant Growth of 4-Hydroxy Estradiol-Transformed Mammary Epithelial Cells

The purpose of this study was to investigate the effects of 17-β-estradiol (E2)-induced reactive oxygen species (ROS) on the induction of mammary tumorigenesis. We found that ROS-induced by repeated exposures to 4-hydroxy-estradiol (4-OH-E2), a predominant catechol metabolite of E2, caused transformation of normal human mammary epithelial MCF-10A cells with malignant growth in nude mice. This was evident from inhibition of estrogen-induced breast tumor formation in the xenograft model by both overexpression of catalase as well as by co-treatment with Ebselen. To understand how 4-OH-E2 induces this malignant phenotype through ROS, we investigated the effects of 4-OH-E2 on redox-sensitive signal transduction pathways. During the malignant transformation process we observed that 4-OH-E2 treatment increased AKT phosphorylation through PI3K activation. The PI3K-mediated phosphorylation of AKT in 4-OH-E2-treated cells was inhibited by ROS modifiers as well as by silencing of AKT expression. RNA interference of AKT markedly inhibited 4-OH-E2-induced in vitro tumor formation. The expression of cell cycle genes, cdc2, PRC1 and PCNA and one of transcription factors that control the expression of these genes – nuclear respiratory factor-1 (NRF-1) was significantly up-regulated during the 4-OH-E2-mediated malignant transformation process. The increased expression of these genes was inhibited by ROS modifiers as well as by silencing of AKT expression. These results indicate that 4-OH-E2-induced cell transformation may be mediated, in part, through redox-sensitive AKT signal transduction pathways by up-regulating the expression of cell cycle genes cdc2, PRC1 and PCNA, and the transcription factor – NRF-1. In summary, our study has demonstrated that: (i) 4-OH-E2 is one of the main estrogen metabolites that induce mammary tumorigenesis and (ii) ROS-mediated signaling leading to the activation of PI3K/AKT pathway plays an important role in the generation of 4-OH-E2-induced malignant phenotype of breast epithelial cells. In conclusion, ROS are important signaling molecules in the development of estrogen-induced malignant breast lesions.

Genomic variation of HIV-1 and its effects on drug resistance and molecular epidemiology analyses

In the first part of this study human immunodeficiency virus type 1 (HIV-1) proviral DNA sequences derived from 201 clones of the C2-V3 env region and the first exon of the tat gene were obtained from six MV-1 infected heterosexual couples. These molecular data were used to confirm the epidemiological relationships. The ability of the molecular data to draw such conclusions was also tested with multiple phylogenetic analyses. The tat region was much more useful in establishing epidemiological relationships than the commonly used C2-V3.^ Subsequently, using nucleotide sequences from the first exon of the Tat gene, we tested the hypothesis that a Florida dentist (a common source) infected five of his patients in the course of dental procedures, against the null hypothesis that the dentist and each individual of the dental group independently acquired the virus within the local community. Multiple phylogenetic analyses demonstrated that the sequences of the five patients were significantly more related to each other than to sequences of the controls. Our results using Tat sequences, combined with envelope sequence data, strongly support a common phylogenetic epidemiological relationship among these five patients.^ A third study is presented, which deals with the effects of genomic variations in drug resistance. HIV-1 reverse transcriptase (RT) mutations were detected in DNA from peripheral blood mononuclear cells from 11 of 12 HIV-infected children after 11-20 months of zidovudine monotherapy. The codon 41/215 mutant combination was associated with general decline in health status. Patients developing the codon 70 mutation tended to have a better health status. ^

Safety habits promoted by Hispanic parents for school-aged and adolescent children

Accidents are the leading cause of death among children. Compliance with safety measures have been shown to reduce morbidity and mortality in children. However, Hispanic parents and children have not been adequately studied in the literature in regard to trauma and safety habits utilized. In this exploratory-descriptive study, a convenience sample of 48 Hispanic parents were questioned about their child's activities. The purpose was to determine what safety equipment was used during these activities and how often they were used. Responses to an English/Spanish questionnaire were summarized by frequencies and percentages. Findings suggested that these Hispanic children were at risk for injury due to a low percentage of children wearing the necessary protective equipment. Therefore, education must stress consistent use of safety equipment if injuries are to be prevented. ^

Health beliefs and health care options of disparate black communities in the United States

According to the 1999 U.S. Census, there were approximately thirty-three million African Americans and approximately 1.8 million non-Hispanic black immigrants in the United States. The 1997 U.S. Census estimated that there were as many as 554,000 foreign-born Haitians and 505,000 foreign-born Jamaicans living in the United States, mainly residing in Florida and New York. The U.S. Census claims that blacks are one of the largest emerging ethnic groups in America constituting at least twelve percent of this country's population. Because of this increase, their specific health beliefs and health care options are increasingly nationally significant. ^ In the present intra-black and inter-ethnic study, two hundred seventy African Americans, Haitian immigrants, and Jamaican immigrants residing in South Florida were quantitatively and qualitatively surveyed in order to investigate their health beliefs and health care options. According to the reviewed literature, the three black ethnic groups researched in this study have not been compared or contrasted before in relation to these beliefs and health care choices. ^ As was discovered by the present research, differing health beliefs and health care options were the cultural products of the ethnic differences of the researched communities. It was expected that differing health beliefs among the researched black groups might indicate disparate patterns of health care utilization of either western or non-western models. Additionally, it was projected that by investigating the health beliefs and the health care options of these emerging black ethnic groups, western health care providers in the United States could become better versed in medically servicing growing ethnically-disparate black populations. The study yielded results about the researched groups that supported major findings in the reviewed literature. The data were reported and examined, and theoretical generalizations from the data were discussed. The most important of these findings was that, within a race, health beliefs and health care options were determined by specific ethno-cultural variables dependent on national origins. ^

Longitudinal effects of family factors on alcohol use and alcohol-related problems among males from pre-adolescence to adulthood

The goal of this study was to examine the longitudinal effects of five family factors on alcohol use among adolescent males. The family factors included familism (family pride, loyalty, and cohesion), parent derogation (being put down by parents), parent/child communication, family alcohol problems and family drug problems. The study focused on the effects of the family factors reported by a sample of 451 White-non-Hispanic and African American males during early and mid-adolescence on (1) the intensity of alcohol use in mid-adolescence, and (2) the number of problems associated with alcohol use during the transition to young adulthood. The study also explored racial differences in the effects of the family factors. The data for this study were derived from a two-phase longitudinal epidemiologic cohort study of male and female adolescents enrolled in middle schools in Miami, FL. Data were collected at four points between 1990 and 2001. Linear and logistical regressions were used to analyze the effects of the family variables on the dependent variables. ^ The results of the analyses indicated that all of the family variables except family drug problems were statistically significant predictors of the level of alcohol use and alcohol-related problems. Familism had a moderate influence on both of the dependent variables at all data points, while parent derogation, parent/child communication and family alcohol problems were weak predictors. While the family factors varied by race, their impact on the dependent variables did not vary substantially. ^ This study had methodological shortcomings related to measurement and design that may have contributed to the weak influence of the variables. Future studies should explore possible mediating effects of these variables, and should employ more sensitive measures that are culturally appropriate. The results suggest that, since early family factors have long-term effects on children's substance-using behaviors, the family environment should be addressed in prevention and intervention efforts. ^

The relationship of spirituality and the health promoting behaviors of diet and exercise of African -American women

Public health data show that African-Americans have not adopted health-promoting behaviors of diet and exercise. Spirituality, important in the lives of many African-American women, may be associated with health-promoting behaviors. This study was designed to determine how spirituality relates to health-promoting behaviors in African-American women. Burkhardt's theoretical framework for spirituality was adopted and measures were selected for the three elements of the framework: connectedness with self, others, and environment. ^ The study used a descriptive cross sectional correlational design to investigate the relationships of the independent variables of spirituality, sociodemographics, and BMI, to the dependent variables of diet and exercise, to answer the two primary questions: What is the role of spirituality in impacting the health-promoting behaviors of African-American women? Of the independent variables of spirituality, sociodemographics, and BMI, which are the best predictors of diet and exercise? ^ Central and South Floridian African-American women (n = 260) between 18 and 82 years of age completed several questionnaires: Rosenberg's Self-Esteem Scale, Health Promoting Lifestyle Profile II, Spiritual Perspective Scale, Brief Block Food Frequency, and socio-demographic information. ^ Hierarchical regression identified 40% of the variability of diet to be explained by socio-demographic (education) and spirituality variables (stress management and health responsibility) (p < .001). Twenty-nine percent of the variability of exercise was explained by socio-demographic (education) and spirituality variables (stress management) (p < .001). Canonical correlation analysis identified a significant pair of canonical variates which indicated individuals with good nutrition (.95), increased physical activity (.79), and healthy eating (.42) also had better stress management (.88), better health responsibility (.67), higher spiritual growth (.66), better interpersonal relations (.50), more education (.49), and higher self-esteem (.33). The set explained 57% of the variability (p < .001). ^ An understanding of the factors that influence these women's decision to utilize health-promoting strategies could provide health professionals with additional information to enable them to design culturally and spiritually related health messages for African-American women. The findings of this present study speak of the importance of focusing on stress management, health responsibility, spiritual growth, interpersonal relations and self-esteem along with diet and exercise; this will likely provide improvement in the health-promoting behaviors of African-American women. ^

Health changes in Hispanic older adults in a Spanish arthritis self -management education program

Arthritis is the most common chronic condition affecting older people and is a major cause of limited activity. Arthritis education programs in English have demonstrated a positive impact on health but these programs have not reached the Hispanic communities where arthritis is the leading cause of disability. Minorities, such as Hispanics, have traditionally been reluctant to pursue self-help programs, and have been identified as an under-served population in terms of medical care. This study examined the effectiveness of one community health adult education program targeting Hispanic older adults with arthritis, the Spanish Arthritis Self Management Education Program (SASMEP), by evaluating changes in the participants' general health, pain, disability, self-efficacy, health perceptions, frequency of physician visits, and exercise. A pre and post control group experimental design and analyses of covariance were used to determine the pre and post differences in health status and health behaviors for a group participating in the SASMEP and a group who did not using gender and age as covariates. A repeated measures design was also used, and repeated measures analyses of variance and post hoc tests were done on health status and health behavior data collected pre, post and one-year post education to determine long-term differences. ^ Results indicated the participants' health status significantly improved in general health, significantly decreased in pain, and significantly decreased in arthritic disability immediately following the education. Self-efficacy and health perceptions increased for both groups but not significantly. The participants' health behaviors showed significantly fewer physician visits and significantly increased time spent performing stretching and strengthening exercise and time spent performing aerobic exercise. No group differences were found in the frequency of arthritis physician visits. ^ The improvements seen immediately after the SASMEP participation were not reflected in the post one-year scores. No significant differences were found for the participants' health status or health behaviors one year following the education. Health status and health behaviors did not return below baseline scores after one year suggesting the participants' health, although not improved, did not deteriorate. Therefore, the SASMEP education provided short-term health benefits for older Hispanic adults with arthritis, but not long-term health benefits. ^

The effects of age, ethnicity, sexual dysfunction, urinary incontinence, masculinity, and relationship with the partner on the quality of life of men with prostate cancer

Prostate cancer, the leading cause of cancer in men, has positive survival rates and constitutes a challenge to men with its side effects. Studies have addressed the bivaritate relationships between prostate cancer treatment side effects masculinity, partner relationship, and quality of life (QOL). However, few studies have highlighted the relationships among prostate cancer treatment side effects (i.e., sexual dysfunction, urinary incontinence), masculinity, and relationship with the partner together on QOL in men. Most studies were conducted with predominately Caucasian sample of men. Miami is a unique multiethnic setting that hosts Cuban, Columbian, Venezuelan, Haitian, other Latin American and Caribbean communities that were not represented in previous literature. The purpose of this study was to examine relative contributions of age, ethnicity, sexual dysfunction, urinary incontinence, masculinity, and perception of the relationship with the partner on the quality of life in men diagnosed with prostate cancer. Data were collected using self administered questionnaires measuring demographic variables, sexual and urinary functioning (UCLA PCI), masculinity (CMNI), partner relationship (DAS), and QOL (SF-36). A total of 117 partnered heterosexual men diagnosed with prostate cancer were recruited from four urology clinics in Miami, Florida. Men were 67.47 (SD = 8.42) years old and identified themselves to be of Hispanic origin (54.3 %, n = 63). Findings demonstrated that there was a significant moderate negative relationship between urinary and sexual functioning of men. There was a significant strong negative association between men's perceived relationship with partner and masculinity. There was a weak negative relationship between the partner relationship and QOL. Hierarchal multiple regression showed that the partner relationship (β = -.25, t (91) = -2.28, p = .03) significantly contributed overall to QOL. These findings highlight the importance of the relationship satisfaction in the QOL of men with prostate cancer. Nursing interventions to enhance QOL for these men should consider strengthening the relationship and involving the female partner as an active participant.^