Vasculogenesis: A process of vessel formation and its role during Ewing's sarcoma development

Vasculogenesis is the process by which Endothelial Precursor Cells (EPCs) form a vasculature. This process has been traditionally regarded as an embryological process of vessel formation. However, as early as in the 60's the concept of postnatal vasculogenesis was introduced, with a strong resurface of this idea in recent years. Similarly, previous work on a mouse skin tumor model provided us with the grounds to consider the role of vasculogenesis during tumor formation. ^ We examined the contribution of donor bone marrow (BM)-derived cells to neovascularization in recipient nude mice with Ewing's sarcoma. Ewing's sarcoma is a primitive neuroectodermal tumor that most often affects children and young adults between 5 and 30 years of age. Despite multiple attempts to improve the efficacy of chemotherapy for the disease, the 2-year metastases-free survival rate for patients with Ewing's sarcoma has not improved over the past 15 years. New therapeutic approaches are therefore needed to reduce the mortality rate. ^ The contribution of BM endothelial precursor cells in the development of Ewing's sarcoma was examined using different strategies to track the donor-derived cells. Using a BMT model that takes advantage of MHC differences between donor and recipient mice, we have found that donor BM cells were involved in the formation of Ewing's sarcoma vasculature. ^ Cells responsible for this vasculogenesis activity may be located within the stem cell population of the murine BM. These stem cells would not only generate the hematopoietic lineage but they would also generate ECs. Bone marrow SP (Side Population) cells pertain to a subpopulation that can be identified using flow cytometric analysis of Hoechst 33342-stained BM. This population of cells has HSC activity. We have tested the ability of BM SP cells to contribute to vasculogenesis in Ewing's sarcoma using our MHC mismatched transplant model. Mice transplanted with SP cells developed tumor neovessels that were derived from the donor SP cells. Thus, SP cells not only replenished the hematopoietic system of the lethally irradiated mice, but also differentiated into a non-hematopoietic cell lineage and contributed to the formation of the tumor vasculature. ^ In summary, we have demonstrated that BM-derived cells are involved in the generation of the new vasculature during the growth of Ewing's sarcoma. The finding that vasculogenesis plays a role in Ewing's sarcoma development opens the possibility of using genetically modified BM-derived cells for the treatment of Ewing's sarcomas. ^

Defining barriers in caring for seriously-ill children in a resource-limited setting: An observational study of 2 children's hospitals in Haiti

Background. According to the WHO 2007 country report, Haiti lags behind the Millennium Development Goal of reducing child mortality and maintains the highest under-5 mortality rate in the Western hemisphere. 3 Overall, few studies exist that seek to better grasp barriers in caring for a seriously ill child in a resource-limited setting and only a handful propose sustainable, effective interventions. ^ Objectives. The objectives of this study are to describe the prevalence of serious illnesses among children hospitalized at 2 children's hospitals in Port au Prince, to determine the barriers faced when caring for seriously ill children, and to report hospital outcomes of children admitted with serious illnesses. ^ Methods. Data were gathered from 2 major children's hospitals in Port au Prince, Haiti (Grace Children's Hospital [GCH] and Hopital d l'Universite d'Etat d'Haiti [HUEH]) using a triangulated approach of focus group discussions, physician questionnaires, and retrospective chart review. 23 pediatric physicians participated in focus group discussions and completed a self-administered questionnaire evaluating healthcare provider knowledge, self-efficacy, and perceived barriers relating to the care of seriously ill children in a resource-limited setting. A sample of 240 patient charts meeting eligibility criteria was abstracted for pertinent elements including sociodemographics, documentation, treatment strategies, and outcomes. Factors associated with mortality were analyzed using χ2 test and Fisher exact test [Minitab v.15]. ^ Results. The most common primary diagnoses at admission were gastroenteritis with moderate dehydration (35.5%), severe malnutrition (25.8%), and pneumonia (19.3%) for GCH, and severe malnutrition (32.6%), sepsis (24.7%), and severe respiratory distress (18%) for HUEH. Overall, 12.9% and 27% of seriously ill patients presented with shock to GCH and HUEH, respectively. ^ Shortage of necessary materials and equipment represented the most commonly reported limitation (18/23 respondents). According to chart data, 9.4% of children presenting with shock did not receive a fluid bolus, and only 8% of patients presenting with altered mental status or seizures received a glucose check. 65% of patients with meningitis did not receive a lumbar puncture due to lack of materials. ^ Hospital mortality rates did not differ by gender or by institution. Children who died were more likely to have a history of prematurity (OR 4.97 [95% CI 1.32-18.80]), an incomplete vaccination record (OR 4.05 [95% CI 1.68-9.74]), or a weight for age ≤3rd percentile (OR 6.1 [95% CI 2.49-14.93]. Case-fatality rates were significantly higher among those who presented with signs of shock compared with those who did not (23.1% vs. 10.7%, RR=2.16, p=0.03). Caregivers did not achieve shock reversal in 21% of patients and did not document shock reversal in 50% of patients. ^ Conclusions. Many challenges face those who seek to optimize care for seriously ill children in resource-limited settings. Specifically, in Haiti, qualitative and quantitative data suggest major issues with lack of supplies, pre-hospital factors, including malnutrition as a comorbidity, and early recognition and management of shock. A tailored intervention designed to address these issues is needed in order to prospectively evaluate improvements in child mortality in a high-risk population.^

The burden of parainfluenza virus infection in patients with hematological malignancy and hematopoietic stem cell transplant (HSCT) recipients in the absence of active immunization and approved therapy: The role of infection control

Background. Community respiratory viruses, mainly RSV and influenza, are significant causes of morbidity and mortality in patients with leukemia and HSCT recipients. The data on impact of PIV infections in these patients is lacking. Methods. We reviewed the records of patients with leukemia and HSCT recipients who developed PIV infection from Oct'02–Nov'07 to determine the outcome of such infections. Results. We identified 200 patients with PIV infections including 80(40%) patients with leukemia and 120 (60%) recipients of HSCT. Median age was 55 y (17-84 y). As compared to HSCT recipients, patients with leukemia had higher APACHE II score (14 vs. 10, p<0.0001); were more likely to have ANC<500 (48% vs. 10%, p<0.0001) and ALC<200 (45% vs. 23.5%, p=0.02). PIV type III was the commonest isolate (172/200, 86%). Most patients 141/200 (70%) had upper respiratory infection (URI), and 59/200 (30%) had pneumonia at presentation. Patients in leukemia group were more likely to require hospitalization due to PIV infection (77% vs. 36% p=0.0001) and were more likely to progress to pneumonia (61% vs. 39%, p=0.002). Fifty five patients received aerosolized ribavirin and/or IVIG. There were no significant differences in the duration of symptoms, length of hospitalization, progression to pneumonia or mortality between the treated verses untreated group. The clinical outcome was unknown in 13 (6%) patients. Complete resolution of symptoms was noted in 91% (171/187) patients and 9% (16/187) patients died. Mortality rate was 17% (16/95) among patients who had PIV pneumonia, with no significant difference between leukemia and HSCT group (16% vs. 17%). The cause of death was acute respiratory failure and/or multi-organ failure in (13, 81%) patients. Conclusions. Patients with leukemia and HSCT could be at high risk for serious PIV infections including PIV pneumonia. Treatment with aerosolized ribavirin and/or IVIG may not have significant effect on the outcome of PIV infection.^

Early stage breast cancer and comorbidities: Their impact on breast cancer disease-free survival differences by ethnicity

The retrospective cohort study examined the association between the presence of comorbidities and breast cancer disease-free survival rates among racial/ethnic groups. The study population consisted of 2389 women with stage I and II invasive breast cancer who were diagnosed and treated at the M.D. Anderson Cancer Center between 1985 and 2000. It has been suggested that as the number of comorbidities increases, breast cancer mortality increases. It is known that African Americans and Hispanics are considered to be at a higher risk for comorbid conditions such as hypertension and diabetes compared to Caucasian women (23) (10). When compared to Caucasian women, African American women also have a higher breast cancer mortality rate (1). As a result, the study also examined whether comorbid conditions contribute to racial differences in breast cancer disease-free survival. Among the study population, 24% suffered from breast cancer recurrence, 6% died from breast cancer and 24% died from all causes. The mean age was 56 with 41% of the population being women between the ages of 40-55. One or more comorbidities were reported in 84 (36%) African Americans (OR 1.57; 95% CI 1.19-2.10), 58 (31%) Hispanics (OR 1.25; 95% CI 0.90-1.74) compared to the reference group of 531 (27%) Caucasians. Additionally, African American women were significantly more likely to suffer from either a breast cancer recurrence or breast cancer death (OR 1.5; 95% CI 0.70-1.41) when compared to Caucasian women. Multivariate analysis found hypertension (HR 1.22; 95% CI 0.99-1.49; p<0.05) to be statistically significant and a potential prognostic tool for disease-free survival with African American women (OR 2.96; 95% 2.25-3.90) more likely to suffer from hypertension when compared to Caucasian women. When compared to Caucasian women, Hispanics were also more likely to suffer from hypertension (OR 1.33; 95% CI 0.96-1.83). This suggests that comorbid conditions like hypertension could account for the racial disparities that exist when comparing breast cancer survival rates. Future studies should investigate this relationship further.^

Non-staphylococcal infections of cardiac implantable electronic devices

Background. The number of infections of cardiac implantable electronic devices (CIED) continues to escalate out of proportion to the increase rate of device implantation. Staphylococcal organisms account for 70% to 90% of all CIED infections. However, little is known about non-staphylococcal infections, which have been described only in case reports, small case series or combined in larger studies with staphylococcal CIED infections, thereby diluting their individual impact. ^ Methods. A retrospective review of hospital records of patients admitted with a CIED-related infections were identified within four academic hospitals in Houston, Texas between 2002 and 2009. ^ Results. Of the 504 identified patients with CIED-related infection, 80 (16%) had a non-staphylococcal infection and were the focus of this study. Although the demographics and comorbities of subjects were comparable to other reports, our study illustrates many key points: (a) the microbiologic diversity of non-staphylococcal infections was rather extensive, as it included other Gram-positive bacteria like streptococci and enterococci, a variety of Gram-negative bacteria, atypical bacteria including Nocardia and Mycobacteria, and fungi like Candida and Aspergillus; (b) the duration of CIED insertion prior to non-staphylococcal infection was relatively prolong (mean, 109 ± 27 weeks), of these 44% had their device previously manipulated within a mean of 29.5 ± 6 weeks; (c) non-staphylococcal organisms appear to be less virulent, cause prolonged clinical symptoms prior to admission (mean, 48 ± 12.8 days), and are associated with a lower mortality (4%) than staphylococcal organisms; (d) thirteen patients (16%) presented with CIED-related endocarditis; (e) although not described in prior reports, we identified 3 definite and 2 suspected cases of secondary Gram-negative bacteremia seeding of the CIED; and (f) inappropriate antimicrobial coverage was provided in approximately 50% of patients with non-staphylococcal infections for a mean period of 2.1 days. ^ Conclusions. Non-staphylococcal CIED-related infections are prevalent and diverse with a relatively low virulence and mortality rate. Since non-staphylococcal organisms are capable of secondarily seeding the CIED, a high suspicion for CIED-related infection is warranted in patients with bloodstream infection. Additionally, in patients with suspected CIED infection, adequate Gram positive and -negative antibacterial coverage should be administered until microbiologic data become available.^

Factors affecting prenatal care use and pregnancy outcome in Texas: A comparative study among and within Black, Anglo, and Hispanic populations

This research project is a study in the field of public health to test the relationships of demographic, socioeconomic, behavioral, and biological factors with (1) prenatal care use and (2) pregnancy outcome, measured by birth weight. It has been postulated that demographic, socioeconomic, and behavioral factors are associated with differences in the use of prenatal care services. It has also been postulated that differences in demographic, socioeconomic, behavioral, and biological factors result in differences in birth weight. This research attempts to test these two basic conceptual frameworks. At the same time, an attempt is made to determine the population groups and subgroups that are at increased risk (1) of using fewer prenatal care visits, and (2) of displaying a higher incidence of low birth weight babies. An understanding of these relationships of the demographic, socioeconomic, behavioral, and biological factors in the use of prenatal care visits and pregnancy outcome, measured by birth weight, will potentially offer guidance in the planning and policy development of maternal and child health services. The research considers four major components of maternal characteristics: (1) Demographic factors. Ethnicity, household size, maternal parity, and maternal age; (2) Socioeconomic factors. Maternal education, family income, maternal employment, health insurance coverage, and household dwelling; (3) Behavioral factors. Maternal smoking, attendance at child development classes, mother's first prenatal care visit, total number of prenatal care visits, and adequacy of care; and, (4) Biological factors. Maternal weight gain during pregnancy.^ The research considers 16 independent variables and two dependent variables.^ It was concluded that: (1) Generally, differences in demographic, socioeconomic, and behavioral factors were associated with differences in the average number of prenatal care visits between and within population groups and subgroups. The Hispanic mothers were the lowest users of prenatal care services. (2) In some cases, differences in demographic, socioeconomic, behavioral, and biological factors demonstrated differences in the average birth weight of infants between and within population groups and subgroups. (3) Differences in demographic, socioeconomic, behavioral, and biological factors resulted in differences in the rates of low birth weight babies between and within population groups and subgroups. The Black mothers delivered the highest incidence of low birth weight infants.^ These findings could provide guidance in the formulation of public health policies such as MCH services, an increase in the use of prenatal care services by prospective mothers, resulting in reduction of the incidence of low birth weight babies, and consequently aid in reducing the rates of infant mortality. ^

Sickle cell disease: Its signs, symptoms and varied manifestations

Seventy-five sickle cell patients, age 3-36 years from Houston, Texas, participated in the research study to investigate sickle cell manifestations, conducted between November 1989 and August 1990. All the participants were blacks. There were 35 females and 39 males among the participants in this research study. One of the participants did not document the gender.^ The sickle cell history questionnaire was administered to the participants. Data collected from this study were statistically analyzed using frequencies, percentages, crosstabulations and chi-squares.^ Regular source of health care influences the time of diagnosis of sickle cell disease. Early diagnosis of sickle cell disease with proper care and management will reduce the morbidity and mortality rate of the disease.^ Fevers, bacterial infection, pneumoniae, anemiae, pains, ulcers and cardiovascular problems are common causes of hospitalizations. The average length of stay in the hospital on admission were higher among the sickle cell patients than their family members who themselves did not have sickle cell disease. ^

Percutaneous transluminal coronary angioplasty and coronary events in a biethnic Texas community, 1985--1990

The relationship between change in myocardial infarction (MI) mortality rate (ICD codes 410, 411) and change in use of percutaneous transluminal coronary angioplasty (PTCA), adjusted for change in hospitalization rates for MI, and for change in use of aortocoronary bypass surgery (ACBS) from 1985 through 1990 at private hospitals was examined in the biethnic community of Nueces County, Texas, site of the Corpus Christi Heart Project, a major coronary heart disease (CHD) surveillance program. Age-adjusted rates (per 100,000 persons) were calculated for each of these CHD events for the population aged 25 through 74 years and for each of the four major sex-ethnic groups: Mexican-American and Non-Hispanic White women and men. Over this six year period, there were 541 MI deaths, 2358 MI hospitalizations, 816 PTCA hospitalizations, and 920 ACBS hospitalizations among Mexican-American and Non-Hispanic White Nueces County residents. Acute MI mortality decreased from 24.7 in the first quarter of 1985 to 12.1 in the fourth quarter of 1990, a 51.2% decrease. All three hospitalization rates increased: The MI hospitalization rates increased from 44.1 to 61.3, a 38.9% increase, PTCA use increased from 7.1 to 23.2, a 228.0% increase, and ACBS use increased from 18.8 to 29.5, a 56.6% increase. In linear regression analyses, the change in MI mortality rate was negatively associated with the change in PTCA use (beta = $-$.266 $\pm$.103, p = 0.017) but was not associated with the changes in MI hospitalization rate and in ACBS use. The results of this ecologic research support the idea that the increasing use of PTCA, but not ACBS, has been associated with decreases in MI mortality. The contrast in associations between these two revascularization procedures and MI mortality highlights the need for research aimed at clarifying the proper roles of these procedures in the treatment of patients with CHD. The association between change in PTCA use and change in MI mortality supports the idea that some changes in medical treatment may be partially responsible for trends in CHD mortality. Differences in the use of therapies such as PTCA may be related to differences between geographical sites in CHD rates and trends. ^

Joint effects of pulmonary function and aerobic power on survival in a cohort of healthy adults

Objective measurements of physical fitness and pulmonary function are related individually to long-term survival, both in healthy people and in those who are ill. These factors are furthermore known to be related to one another physiologically in people with pulmonary disease, because advanced pulmonary disease causes ventilatory limitation to exercise. Healthy people do not have ventilatory limitation to exercise, but rather have ventilatory reserve. The relationship between pulmonary function and exercise performance in healthy people is minimal. Exercise performance has been shown to modify the effect of pulmonary function on mortality in people with chronic obstructive pulmonary disease, but the relationship between these factors in healthy people has not been studied and is not known. The purpose of this study is to quantify the joint effects of pulmonary function and exercise performance as these bear on mortality in a cohort of healthy adults. This investigation is an historical cohort study over 20 years of follow-up of 29,624 adults who had complete preventive medicine, spirometry and treadmill stress examinations at the Cooper Clinic in Dallas, Texas.^ In 20 years of follow-up, there were 738 evaluable deaths. Forced expiratory volume in one second (FEV$\sb1$) percent of predicted, treadmill time in minutes percent of predicted, age, gender, body mass index, baseline smoking status, serum glucose and serum total cholesterol were all significant, independent predictors of mortality risk. There were no frank interactions, although age had an important increasing effect on the risk associated with smoking when other covariates were controlled for in a proportional-hazards model. There was no confounding effect of exercise performance on pulmonary function. In agreement with the pertinent literature on independent effects, each unit increase in FEV$\sb1$ percent predicted was associated with about eight tenths of a percent reduction in adjusted mortality rate. The concept of physiologic reserve is useful in interpretation of the findings. Since pulmonary function does not limit exercise tolerance in healthy adults, it is reasonable to expect that exercise tolerance would not modify the effect of pulmonary function on mortality. Epidemiologic techniques are useful for elucidating physiological correlates of mortality risk. ^

AN ATTEMPT TO MEASURE FOOD SAFETY STATUS

The main objective of this study was to attempt to develop some indicators for measuring the food safety status of a country. A conceptual model was put forth by the investigator. The assumption was that food safety status was multifactorily influenced by medico-health levels, food-nutrition programs, and consumer protection activities. However, all these in turn depended upon socio-economic status of the country.^ Twenty-six indicators were reviewed and examined. Seventeen were first screened and three were finally selected, by the stepwise multiple regression analysis, to reflect the food safety status. Sixty-one countries/areas were included in this study.^ The three indicators were life expectancy at birth with multiple correlation coefficient (R2 = 34.62%), adult literacy rate (R2 = 29.66%), and child mortality rate for ages 1-4 (R2 = 9.99%). They showed a cumulative R2 of 57.79%. ^

A DESCRIPTION AND EVALUATION OF EDUCATIONAL PROGRAMS FOR HEALTH MANPOWER IN NIGERIA

A descriptive study of the current educational programs of selected health personnel in Nigeria was made in 1986. Data on the content of educational programs was obtained from personal communication with the Heads of the various institutions and from their published materials (catalogs, course outlines and program descriptions). Adequacy of these programs was judged in the light of current health problems and needs of the population. Evaluation was based on the following criteria: (a) Selection of students to maximize their usefulness in the provision of health care. (b) Relevance of the curriculum to the tasks the trainee will be called upon to perform. (c) Types of courses that focus on community health needs. Using official reports, the health situation in the country was described to give a relative priority of health services.^ Findings indicate the following: (1) Health conditions in Nigeria are related to a high prevalence of illness and disease, unsanitary living conditions, a high ratio of infant mortality and a shortage of public health services. Priority needs for improvement call for attitudinal and environmental changes. (2) All health training programs have improved the relevance of education to community health needs by strengthening practical field experience, and teaching those courses which focus on disease prevention. (3) Prospective nurses and community health workers are selected on the basis of a number of personal and intellectual characteristics, but academic performance alone is the criterion for medical students. (4) The curriculum in the medical school needs to be restructured to cut back on time devoted to enriching the medical "background". Basic sciences need better integration with hospital work. (5) Managerial and organization courses have been well incorporated into the nursing and community health workers' curricula. (6) There is a marked overlap in the tasks the community health workers are expected to perform. This causes some redundancy in having four separate categories of these health personnel. ^

STRATEGIES FOR THE TRANSFER OF APPROPRIATE TECHNOLOGY TO DEVELOPING COUNTRIES: THE IMPLEMENTATION AND DEVELOPMENT OF ENVIRONMENTAL HEALTH PROGRAMS IN TUNISIA

This dissertation focuses on Project HOPE, an American medical aid agency, and its work in Tunisia. More specifically this is a study of the implementation strategies of those HOPE sponsored projects and programs designed to solve the problems of high morbidity and infant mortality rates due to environmentally related diarrheal and enteric diseases. Several environmental health programs and projects developed in cooperation with Tunisian counterparts are described and analyzed. These include (1) a paramedical manpower training program; (2) a national hospital sanitation and infection control program; (3) a community sewage disposal project; (4) a well reconstruction project; and (5) a solid-waste disposal project for a hospital.^ After independence, Tunisia, like many developing countries, encountered several difficulties which hindered progress toward solving basic environmental health problems and prompted a request for aid. This study discusses the need for all who work in development programs to recognize and assess those difficulties or constraints which affect the program planning process, including those latent cultural and political constraints which not only exist within the host country but within the aid agency as well. For example, failure to recognize cultural differences may adversely affect the attitudes of the host staff towards their work and towards the aid agency and its task. These factors, therefore, play a significant role in influencing program development decisions and must be taken into account in order to maximize the probability of successful outcomes.^ In 1969 Project HOPE was asked by the Tunisian government to assist the Ministry of Health in solving its health manpower problems. HOPE responded with several programs, one of which concerned the training of public health nurses, sanitary technicians, and aids at Tunisia's school of public health in Nabeul. The outcome of that program as well as the strategies used in its development are analyzed. Also, certain questions are addressed such as, what should the indicators of success be, and when is the time right to phase out?^ Another HOPE program analyzed involved hospital sanitation and infection control. Certain generic aspects of basic hospital sanitation procedures were documented and presented in the form of a process model which was later used as a "microplan" in setting up similar programs in other Tunisian hospitals. In this study the details of the "microplan" are discussed. The development of a nation-wide program without any further need of external assistance illustrated the success of HOPE's implementation strategies.^ Finally, although it is known that the high incidence of enteric disease in developing countries is due to poor environmental sanitation and poor hygiene practices, efforts by aid agencies to correct these conditions have often resulted in failure. Project HOPE's strategy was to maximize limited resources by using a systems approach to program development and by becoming actively involved in the design and implementation of environmental health projects utilizing "appropriate" technology. Three innovative projects and their implementation strategies (including technical specifications) are described.^ It is advocated that if aid agencies are to make any progress in helping developing countries basic sanitation problems, they must take an interdisciplinary approach to progrm development and play an active role in helping counterparts seek and identify appropriate technologies which are socially and economically acceptable. ^

Genetic variants associated with metastatic prostate cancer

Introduction. Distant metastasis remains the leading cause of death among prostate cancer patients. Several genetic susceptibility loci associated with Prostate cancer have been identified by the Genome Wide Association Studies (GWAS). To date, few studies have explored the ability of these SNPs to identify metastatic prostate cancer. Based on the identification of genetic variants as predictors of aggressive disease, a case comparison study of prostate cancer patients was designed to explore the association of 96 GWAS single nucleotide polymorphisms (SNPs) with metastatic disease. ^ Method. 1242 histologically confirmed prostate cancer patients, with and without metastatic disease, were enrolled into the study. Data were collected from personal interviews, hospital database and abstraction of medical records. Ninety six SNPs identified from GWAS studies based on their associations with prostate cancer risk were genotyped in the study population. Univariate and multivariate logistic regression analyses were used to explore the relationships of the variants with metastatic prostate cancer in Whites and African American men. ^ Results. Four SNPs showed independent associations with metastatic prostate cancer (rs721048 in EHBP1 (2p15), rs3025039 in VEGF (6p12), rs11228565 in Intergenic(11q13.2) and rs2735839 in KLK3(19q13.33)) in the White population. For SNP rs2735839 in KLK3, genotype GA was 1.71 times as likely to be associated with metastatic prostate cancer diagnosis as genotype AA after adjusting for other significant SNPs and covariates (95% CI, 1.12-2.60; p=0.012). In men of African descent, three SNPs: rs1512268 in NKX3-1(8p21.2), rs12155172 in intergenic (7p15.3) & rs10486567 in JAZF1 (7p15.2) were positively associated with metastatic disease in the multivariate analysis. The strongest SNP was rs1512268 heterozygous genotype AG in NKX3-1(8p21.2) which was associated with 3.97-fold increased risk of metastatic prostate cancer diagnosis (95% CI, 1.69-9.34; p =0.002). ^ Conclusion. Genetic variants associated with metastatic prostate cancer were different in Whites and African American men. Given the high mortality rate recorded in men diagnosed with metastatic prostate tumor, further studies are needed to validate associations and establish their clinical application.^

Prevention of birth defects in a national study

The following analyses covered two main objectives focused on the prevention of and identification of risk factors for birth defects, the leading cause of infant mortality. All analyses utilized data from the National Birth Defects Prevention Study (NBDPS), an ongoing, population-based, case-control study of major structural birth defects. ^ The first objective was to identify predictors of folic acid supplementation among women of reproductive age. To meet this objective, a previous analysis of potential predictors of periconcecptional folic acid use in the NBDPS was repeated using data from more recent years (1997-2000 versus 2001-2005). The results of these analyses were consistent with the initial analyses, indicating that folic acid use is associated with maternal race/ethnicity, age, education, pregnancy awareness, smoking status, first prenatal care visit, previous live births, and fertility treatments). In addition, data from NBDPS controls were used to identify predictors of preconceptional folic acid use, since supplementation is optimally initiated prior to pregnancy (rather than after conception). These analyses indicated that maternal race/ethnicity, education, age, nativity, employment status, income, number of dependents, smoking, and birth control are significantly associated with preconceptional folic acid supplementation. Ultimately the results of these analyses can be used to guide the development of targeted interventions for preconceptional folic acid use. ^ The second objective was to investigate the association between parental Hispanic acculturation and the risk of gastroschisis, a congenital malformation of the abdominal wall, in offspring. Significant association were not observed for mothers < 20 years of age at conception. Among mothers ≥ 20 years of age, white parents were at a decreased risk of having a child with gastroschisis as compared to Hispanic parents who were born in the United States (US) [odd ratios (ORs) ranging from 0.60 to 0.55] and Hispanics parents who predominantly spoke English (ORs ranging from 0.65 to 0.58). Compared to Hispanic mothers born in the US, the risk of gastroschisis was lower among Hispanic mothers who had lived in the US < 5 years (OR=0.36, 95% CI: 0.42, 0.81) at the time of delivery and Hispanic mothers who migrated to the US at ≥ 20 years of age (OR=0.48, 95% CI: 0.26, 0.89). The results of these analyses provide further evidence that the risk of gastroschisis in offspring is associated with parent Hispanic ethnicity and, among Hispanics, with the degree of parental acculturation. Future studies should focus on characteristic differences between less and more acculturated parents to better understand the relationship between acculturation and gastroschisis.^