991 resultados para Biology, Genetics|Health Sciences, Pathology|Health Sciences, Public Health
Resumo:
This thesis explores adolescent pregnancy in San Jose, Costa Rica and examines a school-based pregnancy prevention intervention. The relationships between school, gender and risk of adolescent pregnancy are also analyzed, and recommendations are made for effective pregnancy prevention programming. The Purral region of Guadalupe on the outskirts of San Jose, Costa Rica, suffers a higher rate of adolescent pregnancy compared to the rest of the country. In response to this problem, the International Health Central American Institute (IHCAI) implemented a sexual health education program in two local secondary schools in 2006. Very little information about the program is available. It is known that the program was initially evaluated through assessments of the participants’ knowledge before and after the educational sessions. There was no evaluation of the youth attitudes or behaviors, adolescent pregnancies, or long-term impact. The author worked with IHCAI in San Jose, Costa Rica to perform an assessment of the longer term effects of this sexual health education program. They developed a questionnaire to evaluate the knowledge, attitudes, and behaviors surrounding sexual health of youth in the Purral community. Researchers at IHCAI later used this survey to collect data from adolescents who had participated in the educational intervention and those who had not. This thesis analyzes the data collected by IHCAI to assess the effectiveness of the - 2 - educational intervention and the influence of other factors on the knowledge, attitudes, and behaviors of adolescents in the Purral region. The thesis begins with an overview of adolescent pregnancy, Costa Rica and the Purral region, and a description of the education intervention implemented by IHCAI. The research goal, logic model, and methods are then described. The results are reported, and the thesis then concludes with discussion of the results as well as study limitations and recommendations for future research and intervention. This thesis will be used to guide IHCAI’s continuation and expansion of adolescent pregnancy prevention programming.
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The purpose of this study was to determine whether depression is a factor in explaining the difference in sex behaviors among adolescents with different ethnic backgrounds, family and school contexts. We hypothesize that adolescents with a higher number of depressive symptoms are more likely to engage in sexual risk behaviors than adolescents with fewer depressive symptoms. Further, adolescent depression and sexual behaviors are mediated or moderated by individual characteristics, family and school contexts. ^ Background. large ethnic disparities exist in adolescent engagement in risky sexual behaviors, yet, there is little in the literature that explains these disparities. Studies of sexual behavior of youths abound; yet, there is little literature on the prevalence and correlates of depression or the association between depression and sexual behaviors among different ethnic groups. Objectives. (1) To determine ethnic differences in the prevalence of depressive symptoms using data collected through the National Longitudinal Study of Adolescent Health (Add Health). (2) To determine predictors of sex risk behaviors among adolescents, including the role of depression. (3) To identify predictors of depression among these adolescents. Methods. Add Health data from wave 1 and wave 2 interviews of 7th–12th graders were analyzed using multivariate models constructed with both depression and sexual behavior as outcome variables. Logistic regression models determined whether and to what extent the independent variables, including depression, sex behaviors, demographic factors, individual and family characteristics, and school context were related to the probability of engaging in risky sexual behaviors. Results. Ethnic differences in depressive symptoms did not persist after demographic and contextual variables were included in the model. Sex behaviors all shared the hypothesized relationship with depressive symptoms. The odds of risky sex behaviors increased as number of depressive symptoms increased. Depression was predicted by marijuana use and having a serious argument with father for males at Wave 1 and by age and future orientation for females. Wave 2 depression was predicted by Wave 1 depression. ^
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Repeated treatment with psychostimulants produces behavioral sensitization that results in increased locomotor responses so that lower drug doses are required to obtain the same effect and cross-sensitization with other stimulants. Methylphenidate (MPD; Ritalin) is most frequently prescribed to treat children having attention deficit hyperactivity disorder (ADHD), a syndrome with onset in childhood characterized by high levels of inattention, hyperactivity, and impulsivity. Little is known of the consequences involving the long-term use of MPD as treatment for ADHD. This study investigates if there are age, genetic/strain, and sex differences in the prolonged exposure to MPD and cross-sensitization with amphetamine. The objective is to determine whether (a) early exposure to MPD in adolescent rats increases their sensitivity to the drug when they are adult rats, (b) there are strain and sex differences in the response to MPD, and (c) treatment with MPD in adolescent and adult Wistar-Kyoto (WKY), spontaneously hyperactive/hypertensive rat (SHR), and Sprague-Dawley (SD) rat results in cross-sensitization with amphetamine. The hypotheses are that (1) early exposure to MPD in adolescent rats increases their sensitivity to the drug when they reach adulthood, and that this hypersensitivity is dose-, strain-, and sex-dependent and (2) adult rats treated with MPD as adolescents will show a greater cross-sensitization to amphetamine than those adult rats treated with saline as adolescents, and that this cross-sensitization is dose-, strain-, and sex-dependent. The study consists of recording and evaluating locomotor activity of female and male WKY, SHR, and SD rats before and after acute and repeated MPD administration when these rats are young and as adults follows by an amphetamine treatment. Results showed that repeated treatment with MPD elicited behavioral sensitization and cross-sensitization with amphetamine in these animals. The study also found that strain and sex play a crucial role in the differentiated sensitivity to the acute and chronic effects of MPD. The development of behavioral sensitization and cross-sensitization are also dependent on the dose of MPD and the age of the rat. ^
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Purpose of the study. The purpose of this randomized controlled clinical trial was to determine if a brief intervention would improve foot self-care behaviors in adult patients with Type 2 diabetes who presented to the emergency department for non-emergent care in a predominantly Hispanic southwestern border community. ^ Methods. A pre-post-test, three-group design was used to compare the foot self-care behaviors of patients who received usual care to those who received lower extremity amputation (LEA) risk assessment and to those who received LEA risk assessment plus a brief foot self-care intervention. After being randomized into 3 groups (N = 167), baseline assessments of demographics, diabetes history, acculturation, and the Summary of Diabetes Self Care Activities (SDSCA) questionnaire and Modified Insulin Management Diabetes Self Efficacy Scale (MIMDSES) were completed in English or Spanish. At one-month, 144 (84%) participants were available for follow-up by the research assistant masked to group assignment. ^ Results. At baseline, significant differences in foot self-care behaviors and self monitoring blood glucose were noted based on ethnicity and gender. Men had significantly lower confidence in their ability to manage their diabetes overall. There was a significant difference between baseline and follow up self reported foot self-care behaviors within the intervention group (t (47) = −4.32, p < .01) and the control group (t (46) = −2.06, p < .05). There were no significant differences between groups for self-reported foot self-care behaviors. There was a significant difference in observed foot self-care behaviors between groups (F(2,135) = 2.99, p < .05). Self-efficacy scores were positively correlated with self-reported self-care behaviors. ^ Conclusions. This predominantly Hispanic population with type 2 diabetes reported performing diabetes self-care behaviors less than five days a week. There were within group changes, but no significant between group changes in reported self-care behaviors. However, at the one month follow up, there were significant differences between groups in observed foot self-care behaviors with the intervention group demonstrating the most accurate behaviors. Differences based on gender and ethnicity emphasize the need to individualize diabetes education. Priorities for culturally competent diabetes education, approaches to increasing self-efficacy and future research directions are suggested. ^
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ErbB2 is an excellent target for cancer therapies because its overexpression was found in about 30% of breast cancers and correlated with poor prognosis of the patients. Unfortunately, current therapies for ErbB2-positive breast cancers remain unsatisfying due to side effects and resistance, and new therapies for ErbB2 overexpressing breast cancers are needed. Peptide/protein therapy using cell-penetrating peptides (CPPs) as carriers is promising because the internalization is highly efficient and the cargos can be bioactive. The major obstacle in using CPPs for therapy is their lack of specificity. We sought to develop a peptide carrier specifically introducing therapeutics to ErbB2-overexpressing breast cancer cells. By modifying the TAT-derived CPP, and attaching anti-HER2/neu peptide mimetic (AHNP), we developed the peptide carrier (P3-AHNP) specifically targeted ErbB2-overexpressing breast cancers in vitro and in vivo. A STAT3 SH2 domain-binding peptide conjugated to this peptide carrier (P3-AHNP-STAT3BP) was delivered preferentially into ErbB2-overexpressing breast cancer cells in vitro and in vivo. P3-AHNP-STAT3BP inhibited growth and induced apoptosis in vitro, with ErbB2-overexpressing 435.eB cells being more sensitive than the ErbB2-lowexpressing MDA-MB-435 cells. P3-AHNP-STAT3BP preferentially accumulated and inhibited growth in 435.eB xenografts, comparing with MDA-MB-435 xenografts or normal tissues with low levels of ErbB2. This ErbB2-targeting peptide delivery system provided the basis for future development of novel cancer target-specific treatments with low toxicity to normal cells. ^ Another urgent issue in treating ErbB2-positive breast cancers is trastuzumab resistance. Trastuzumab is the only FDA-approved ErbB2-targeting antibody for treatment of metastatic breast cancers overexpressing ErbB2, and has remarkable therapeutic efficacy in certain patients. The overall trastuzumab response rate, however, is limited, and understanding the mechanisms of trastuzumab resistance is needed to overcome this problem. We report that PTEN activation contributes to trastuzumab's anti-tumor activity. Trastuzumab treatment quickly inactivated Src, which reduced PTEN tyrosine phosphorylation, increased PTEN membrane localization and its phosphatase activity in cancer cells. Reducing PTEN expression in breast cancer cells by antisense oligonucleotides conferred trastuzumab resistance in vitro and in vivo. Importantly, PI3K inhibitors sensitized PTEN-deficient breast cancers to the growth inhibition by trastuzumab in vitro and in vivo, suggesting that combination therapies with PI3K inhibitors plus trastuzumab could overcome trastuzumab resistance. ^
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Bortezomib (VELCADE™, formerly known as PS-341) is a selective and potent inhibitor of the proteasome that was recently FDA-approved for the treatment of multiple myeloma. Despite its success in multiple myeloma and progression into clinical trials for other malignancies, bortezomib's exact mechanism of action remains undefined. The major objective of this study was to evaluate the anticancer activity of this drug using in vitro and in vivo pancreatic cancer models and determine whether bortezomib-induced apoptosis occurs via induction of endoplasmic reticular (ER) stress. The investigation revealed that bortezomib inhibited tumor cell proliferation via abrogation of cdk activity and induced apoptosis in pancreatic cancer cell lines. I hypothesized that bortezomib-induced apoptosis was triggered by a large accumulation ubiquitin-conjugated proteins that resulted in ER stress. My data demonstrated that bortezomib induced a unique type of ER stress in that it inhibited PKR-like ER kinase (PERK) and subsequent phosphorylation of eukaryotic initiation factor 2α (eif2α), a key event in translational suppression. The combined effects of proteasome inhibition and the failure to attenuate translation resulted in an accumulation of aggregated proteins (proteotoxicity), JNK activation, cytochrome c release, caspase-3 activation, and DNA fragmentation. Bortezomib also enhanced apoptosis induced by other agents that stimulated the unfolded protein response (UPR), demonstrating that translational suppression is a critical cytoprotective mechanism during ER stress. Tumor cells attempt to survive bortezomib-induced ER stress by sequestering aggregated proteins into large structures, termed aggresomes. Since histone deacetylase 6 (HDAC6) is essential for aggresome formation, tumor cells may be sensitized to bortezomib-induced apoptosis by blocking HDAC function. My results demonstrated that HDAC inhibitors disrupted aggresome formation and synergized with bortezomib to induce apoptosis in pancreatic cancer or multiple myeloma cells in vitro and in orthotopic pancreatic tumors in vivo. Taken together, my data establish a mechanistic link between bortezomib-induced aggresome formation, ER stress, and apoptosis and identify a novel therapeutic strategy for the treatment of pancreatic cancer and other hematologic and solid malignancies. ^
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A retrospective cohort study was conducted among 1542 patients diagnosed with CLL between 1970 and 2001 at the M. D. Anderson Cancer Center (MDACC). Changes in clinical characteristics and the impact of CLL on life expectancy were assessed across three decades (1970–2001) and the role of clinical factors on prognosis of CLL were evaluated among patients diagnosed between 1985 and 2001 using Kaplan-Meier and Cox proportional hazards method. Among 1485 CLL patients diagnosed from 1970 to 2001, patients in the recent cohort (1985–2001) were diagnosed at a younger age and an earlier stage compared to the earliest cohort (1970–1984). There was a 44% reduction in mortality among patients diagnosed in 1985–1995 compared to those diagnosed in 1970–1984 after adjusting for age, sex and Rai stage among patients who ever received treatment. There was an overall 11 years (5 years for stage 0) loss of life expectancy among 1485 patients compared with the expected life expectancy based on the age-, sex- and race-matched US general population, with a 43% decrease in the 10-year survival rate. Abnormal cytogenetics was associated with shorter progression-free (PF) survival after adjusting for age, sex, Rai stage and beta-2 microglobulin (beta-2M); whereas, older age, abnormal cytogenetics and a higher beta-2M level were adverse predictors for overall survival. No increased risk of second cancer overall was observed, however, patients who received treatment for CLL had an elevated risk of developing AML and HD. Two out of three patients who developed AML were treated with alkylating agents. In conclusion, CLL patients had improved survival over time. The identification of clinical predictors of PF/overall survival has important clinical significance. Close surveillance of the development of second cancer is critical to improve the quality of life of long-term survivors. ^
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In the last thirty years, increasing efforts have been made to reduce the prevalence of adolescent tobacco use in the United States. Although the prevalence has declined dramatically over the past decade, there are still sharp differences in adolescent smoking-initiation rates across racial/ethnic groups. Large-scale surveys frequently assess smoking-related attitudes, self-efficacy, and intentions to explain the differences in smoking rates between African Americans and Whites. However, there is little agreement about which constructs are significant. Moreover, the psychometric properties of smoking-related attitude, self-efficacy, and intention constructs have not been fully examined. More studies are needed to understand existing patterns of tobacco use and to validate and fully exploit the constructs' relationship to adolescent smoking initiation across racial/ethnic groups. ^ This dissertation reports on a secondary analysis of data from a large multi-ethnic convenience sample of sixth- through eighth-grade students in 22 schools in East Texas and the city of Houston. The specific aims of this dissertation were to (1) describe smoking and alternate tobacco product use rates by race/ethnicity, gender, age, and grade level (Article 1); (2) test the factorial validity of smoking-related attitudes, self-efficacy, and intentions using confirmatory factor analysis techniques (Article 2); and (3) test the factorial invariance of smoking-related attitudes, self-efficacy, and intentions between African Americans and Whites (Article 3). ^ The prevalence findings confirm the disparities in tobacco use among African American, Hispanic, and White adolescents that other surveys have reported (Article 1). This study also demonstrates the usefulness of examining use patterns of not only cigarettes but also alternative tobacco products in younger multiethnic populations, as well as of providing epidemiological data estimates about different phases of smoking. The confirmatory factor analysis provides evidence of construct validity of attitude, self-efficacy, and intention scales for the multiethnic sample (Article 2). Finally, the factorial invariance analyses indicates that some measures representing smoking-related attitudes, self-efficacy, and intentions may not be appropriate for use among both African Americans and Whites (Article 3). Additional research is needed to further our understanding of the patterns and predictors of youth tobacco use initiation. ^
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In the United States, approximately 4,000 pregnancies each year are affected by the two most common birth defects, spina bifida and anencephaly. Studies have shown that exposure to environmental chemicals before and after conception may adversely affect reproduction by inducing cell death or dysfunction, which leads to infertility, fetal loss, lowered weight at birth, or birth anomalies in the offspring. The objective of the study was to evaluate the relationship between Neural Tube Defect births and residence at conception in proximity to hazardous waste sites in the Texas-Mexico border region between 1993 and 2000. ^ The study design was a nested matched case-control and utilized secondary data from a project, “The role of chemical and biological factors in the etiology of neural tube birth defects births along the Texas-Mexico Border” (Irina Cech, Principal Investigator). Geographic Information Systems (GIS) database methods were used to compare Neural Tube Defects cases to controls on status of conception residence occurring within a one-mile radius from hazardous waste sites, as compared to conception residence further away. Information on the exposures was obtained from the OnTarget Database and Environment Protection Agency website. Conditional logistic regression was used for the matched case-control study to investigate the relationship between an outcome of being a case or a control and proximity to hazardous waste sites. ^ The result of the study showed a 36 percent non-significant increased risk of having an NTD birth associated with maternal proximity to abandoned hazardous waste sites (95% CI = 0.62–3.02). In addition, there was a 24% non-significant elevated risk of having an NTD birth when living in proximity to air pollutant sites than when living further away (95% CI = 0.67–2.32). Although this study did not find statistically significant associations, it will expand on the existing knowledge of the relationship between NTD and proximity to hazardous waste sites. ^
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Epidemiological evidence suggests that fruit and vegetable intake is negatively associated with the development of several chronic diseases, including heart disease, some cancers and diabetes mellitus. Inadequate consumption of milk during developmental years is associated with osteoporosis. Consumption of fruit, vegetable and milk (FVM) declines from childhood to adolescence. Adolescent eating habits persist into adulthood; thus, understanding psychosocial factors such as self-efficacy, norms and preferences, is important for developing effective interventions. Preferences, one of the most consistent correlates of fruit and vegetable consumption in children and adolescents, may mediate the relationships between self-efficacy and norms and fruit and vegetable consumption. ^ Fifth grade students from one middle school in South Texas were followed for two years. Students completed lunch food records and questionnaires assessing fruit, vegetable and milk self-efficacy and norms and fruit and vegetable preferences. Principal component analyses identified four scales: Fruit Self-Efficacy, Vegetable Self-Efficacy, Fruit and Vegetable Norms, and Milk Influences. Reliability and validity of the four scales and emerging subscales were assessed using Cronbach's alpha and consumption data, respectively. Associations between longitudinal FVM consumption and self-efficacy and norms were tested. Additionally, the influence of preferences on the relationship of self-efficacy, norms and fruit and vegetable consumption was examined. ^ Confirmatory factor analyses confirmed four scales and subscales. Internal consistency and test-retest reliabilities were acceptable. Self-efficacy and norms were related to FVM consumption and changes in fruit and high fat vegetable consumption over the two-year period. While intake over the two-year period differed statistically, eating patterns were stable. Preferences mediated the relation between fruit self-efficacy and FV norms and fruit consumption. ^ In conclusion, self-efficacy and norms about consuming FVM at school appear to influence FVM consumption. Because eating patterns were similar over the two-year period, establishing healthy eating habits in elementary school is important. While FVM self-efficacy and norms influenced FVM consumption in children, only fruit preferences mediated the relationship of fruit consumption, self-efficacy and norms. Since the influences of FVM consumption appear to differ, interventions designed to increase consumption should target these differences and consider the specificity of self-efficacy and norms. ^
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Few studies have investigated causal pathways linking psychosocial factors to each other and to screening mammography. Conflicting hypotheses exist in the theoretic literature regarding the role and importance of subjective norms, a person's perceived social pressure to perform the behavior and his/her motivation to comply. The Theory of Reasoned Action (TRA) hypothesizes that subjective norms directly affect intention; while the Transtheoretical Model (TTM) hypothesizes that attitudes mediate the influence of subjective norms on stage of change. No one has examined which hypothesis best predicts the effect of subjective norms on mammography intention and stage of change. Two statistical methods are available for testing mediation, sequential regression analysis (SRA) and latent variable structural equation modeling (LVSEM); however, software to apply LVSEM to dichotomous variables like intention has only recently become available. No one has compared the methods to determine whether or not they yield similar results for dichotomous variables. ^ Study objectives were to: (1) determine whether the effect of subjective norms on mammography intention and stage of change are mediated by pros and cons; and (2) compare mediation results from the SRA and LVSEM approaches when the outcome is dichotomous. We conducted a secondary analysis of data from a national sample of women veterans enrolled in Project H.O.M.E. (H&barbelow;ealthy O&barbelow;utlook on the M&barbelow;ammography E&barbelow;xperience), a behavioral intervention trial. ^ Results showed that the TTM model described the causal pathways better than the TRA one; however, we found support for only one of the TTM causal mechanisms. Cons was the sole mediator. The mediated effect of subjective norms on intention and stage of change by cons was very small. These findings suggest that interventionists focus their efforts on reducing negative attitudes toward mammography when resources are limited. ^ Both the SRA and LVSEM methods provided evidence for complete mediation, and the direction, magnitude, and standard errors of the parameter estimates were very similar. Because SRA parameter estimates were not biased toward the null, we can probably assume negligible measurement error in the independent and mediator variables. Simulation studies are needed to further our understanding of how these two methods perform under different data conditions. ^
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Background. The rise in survival rates along with more detailed follow-up using sophisticated imaging studies among non-small lung cancer (NSCLC) patients has led to an increased risk of second primary tumors (SPT) among these cases. Population and hospital based studies of lung cancer patients treated between 1974 and 1996 have found an increasing risk over time for the development of all cancers following treatment of non-small cell lung cancer (NSCLC). During this time the primary modalities for treatment were surgery alone, radiation alone, surgery and post-operative radiation therapy, or combinations of chemotherapy and radiation (sequentially or concurrently). There is limited information in the literature about the impact of treatment modalities on the development of second primary tumors in these patients. ^ Purpose. To investigate the impact of treatment modalities on the risk of second primary tumors in patients receiving treatment with curative intent for non-metastatic (Stage I–III) non-small cell lung cancer (NSCLC). ^ Methods. The hospital records of 1,095 NSCLC patients who were diagnosed between 1980–2001 and received treatment with curative intent at M.D. Anderson Cancer Center with surgery alone, radiation alone (with a minimum total radiation dose of at least 45Gy), surgery and post-operative radiation therapy, radiation therapy in combination with chemotherapy or surgery in combination with chemotherapy and radiation were retrospectively reviewed. A second primary malignancy was be defined as any tumor histologically different from the initial cancer, or of another anatomic location, or a tumor of the same location and histology as the initial tumor having an interval between cancers of at least five years. Only primary tumors occurring after treatment for NSCLC will qualified as second primary tumors for this study. ^ Results. The incidence of second primary tumor was 3.3%/year and the rate increased over time following treatment. The type of NSCLC treatment was not found to have a striking effect upon SPT development. Increased rates were observed in the radiation only and chemotherapy plus radiation treatment groups; but, these increases did not exceed expected random variation. Higher radiation treatment dose, patient age and weight loss prior to index NSCLC treatment were associated with higher SPT development. ^
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Background. Heart disease is the leading cause of death and stroke is the third leading cause of deaths for all people in the United States. South Asian Americans have a higher risk of developing cardiovascular diseases than native United States residents. ^ Purpose. This study examines the cardiovascular risk factors in the South Asian immigrant community residing in Southwest Houston. This study also explores the level of health insurance available to the South Asian in Houston. ^ Methods. One hundred sixty-two South Asian patients aged 18 years and older received cardiovascular screening from January 1 st, 2005 to March 31st, 2005 at Ibn Sina Community Clinic; blood pressure was measured twice in both arms after resting five minutes. Height and weight were also recorded. Demographic data was collected through personal interview (questionnaire) and blood samples were drawn to collect laboratory data. ^ Results. There were 162 eligible South Asian patients, among whom 127 (78%) participated in the study. There were no significant differences between the responders and the non-responders in terms of demographics and clinical characteristics. Laboratory data revealed a mean total cholesterol of 201 ± 34 mg/dl, 54 percent had high total cholesterol above 200 mg/dl. The mean fasting glucose was 108 ± 43 mg/dl, and body mass index (BMI) was 28 ± 4 kg/m2. The prevalence of hypertension was comparable with the general U.S. population; 38 percent of the South Asian males and 29 percent of females had hypertension. The prevalence of diabetes was also compared; 21 percent of SA males (3% for white American males) and 7 percent of SA females (2% for white American females) were found to have undiagnosed diabetes. Of the sample 12 percent had both hypertension and diabetes; 21 percent had both hypertension and high BMI, and 19 percent had hypertension and high total cholesterol levels. ^ Conclusion. The present study shows that the South Asians in this sample are at greater risk of developing cardiovascular diseases than other ethnicities. The high prevalence of hypertension, type 2 diabetes, higher total cholesterol levels with overweight and obesity, and less leisure time physical activity are important cardiovascular risk factors for South Asians population. ^
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The purpose of this study, based on secondary data from attendees at a substance abuse clinic for the Kickapoo Healing Grounds in Eagle Pass, Texas, is two fold: (1) to elucidate neuro-behavioral performance of volatile substance abusers in the Kickapoo tribe and (2) to determine factors associated with their treatment completion and rehabilitation as measured by their employment at follow-up. Volatile substance abuse (VSA) is associated with a host of neurological manifestations, and secondary prevention or clinical treatment and rehabilitation remains the mainstay of control efforts. Very little is known about VSA in general, and especially among Native American populations. It is anticipated that the results will help determine and assist other tribes and non-tribal substance abuse centers with treatment planning for volatile substance abusers among Native American populations. ^