Pre-eclampsia in American Indians/Alaska Natives and Whites: The Significance of Body Mass Index.

Introduction The prevalence of pre-eclampsia, a major cause of maternal morbidity, varies by race, being greater in African Americans, and lower in Asians and Hispanics than in White women. Little is known about its prevalence in American Indians/Alaska Natives (AI/ANs). We estimated pre-eclampsia risk in AI/ANs compared to Whites, with consideration of the potential effect of obesity, a major risk factor for pre-eclampsia, and a condition disproportionately affecting AI/AN women. Methods This retrospective cohort study of linked birth-hospital discharge data from Washington State (2003-2013) included all AI/AN women and a sample of White first-time mothers with singleton deliveries. Logistic regression was used to estimate odds ratio (OR) and 95 % confidence intervals (CI) for pre-eclampsia risk in AI/ANs compared to Whites, first controlling for several important risk factors, and subsequently with additional adjustment for pre-pregnancy body mass index (BMI). Results AI/ANs had an increased risk of pre-eclampsia compared to Whites after controlling for all covariates except BMI (OR 1.17, 95 % CI 1.06-1.29). After further adjustment for BMI, the racial disparity in pre-eclampsia risk was greatly attenuated (OR 1.05, 95 % CI 0.95-1.16). Discussion This population-based study suggests that any increased risk in AI/ANs relative to Whites may be at least partly due to differences in BMI.

Synthesis and Investigation of Novel Spiro-isoxazolines as Anti-Cancer Agents.

A series of structurally diverse 4-bromo spiro-isoxazolines possessing a variety of aromatic and aliphatic substituents at the 3 position, were synthesized through a 1,3-dipolar cycloaddition followed by intramolecular cyclization of a pendant hydroxyl or carboxylic acid group. The biochemical antiproliferative activity was evaluated in vitro by using two breast cancer cell lines (MCF-7 and MDA-MB-231) and two prostate cancer cell lines (PC-3 and DU-145) using the MTT viability assay, and the IC50 values were obtained. Spiro-isoxazoline derivatives bearing a p-chloro or an o-dichloro aromatic substituent at the 3-position of the isoxazoline showed considerable antitumor activities in all four cell lines with IC50 value ranging from 43µM to 56µM.

Thermally targeted p21 peptide enhances bortezomib cytotoxicity in androgen-independent prostate cancer cell lines.

Prostate cancer remains one of the most common malignancies in men. Besides surgical resection, treatments for prostate cancer include hormone therapy, chemotherapy, and radiation therapy. Advancement of prostate cancer to an androgen-independent state limits the potential of conventional therapeutic approaches. Bortezomib, an FDA-approved proteosomal inhibitor for the treatment of myeloid leukemia, has been shown to have a positive effect on the inhibition of prostate cancer growth. Unfortunately, bortezomib has a very narrow therapeutic window, which can lead to severe side effects. Elastin-like polypeptide (ELP) is a genetically engineered, thermally responsive macromolecular carrier that enables a targeted delivery of the bound molecule because of its soluble property under normal physiologic conditions. In addition, ELP aggregates in response to mild hyperthermia. Using ELP as a carrier, it is possible to improve the pharmacological properties of the therapeutic drug as well as reduce toxicity in normal tissues. In this work, we have investigated the combination treatment of androgen-independent prostate cancer cells with bortezomib and the C-terminal part of the p21(WAF1/CIP1) protein bound to the ELP carrier. We have found that combination treatment with bortezomib and ELP-bound p21(WAF1/CIP1) protein leads to increased cell cycle arrest as well as apoptosis with respect to single treatments. We believe that this approach represents a promising direction for the treatment of androgen-independent prostate cancer.

Adolescence as a critical stage in the MCH Life Course Model: commentary for the Leadership Education in Adolescent Health (LEAH) interdisciplinary training program projects.

The Life Course Perspective (LCP), or Model, is now a guiding framework in Maternal and Child Health (MCH) activities, including training, supported by the Health Resources and Services Administration's Maternal and Child Health Bureau. As generally applied, the LCP tends to focus on pre- through post-natal stages, infancy and early childhood, with less attention paid to adolescents as either the "maternal" or "child" elements of MCH discourse. Adolescence is a distinct developmental period with unique opportunities for the development of health, competence and capacity and not merely a transitional phase between childhood and adulthood. Adequately addressing adolescents' emergent and ongoing health needs requires well-trained and specialized professionals who recognize the unique role of this developmental period in the LCP.

Attitudes, experience, and anticipation of sex among 5th graders in an urban setting: does gender matter?

To identify gender differences in correlates of anticipation and initiation of sexual activity in the baseline survey of 562 African-American 5th grade students prior to initiation of a school-based pregnancy prevention intervention curriculum. Students from 16 elementary schools were administered the baseline questionnaire during classroom periods. Using these data, binary and ordered logistic regression models were used to analyze the factors affecting virginity and anticipation of sexual activity separately by gender, and tests of interaction between each factor and gender were conducted on the combined sample. More boys than girls had already had sex (18% vs. 5%) and anticipated having sexual intercourse in the next 12 months (56% vs. 22%). Boys and girls also differed in the factors that affected these outcomes. The perception that their neighborhood was safe reduced the odds that boys anticipated sexual activity but was not associated with this outcome among girls. Pubertal knowledge increased the odds of anticipation, but only among boys. Attitudes favoring abstinence decreased anticipation of sex among both genders, but slightly more among girls than boys. Having more frequent parent-child communication about sex was associated with increased anticipation among girls but decreased anticipation among boys. Curriculum based approaches to adolescent pregnancy prevention are appropriate for 5th grade elementary students who may already be anticipating sexual activity in communities with disproportionate rates of teen pregnancy. The design of the interventions should consider the differences in motivating factors by gender.

Relationships of Pubertal Development Among Early Adolescents to Sexual and Nonsexual Risk Behaviors and Caregivers' Parenting Behaviors.

Using a school-based sample of Washington, DC, fifth graders (mean age 10.38, SD = 0.66) and their parents (N = 408), we examined associations of pubertal development with early adolescents' sexual and nonsexual risk behaviors and their caregivers' parenting behaviors; and of these risk behaviors with parenting behaviors. Youths reporting signs of pubertal development were more likely to engage in these risk behaviors than students reporting no signs. Pubertal development was not related to parenting behaviors; however, parents of youths who reported multiple nonsexual risk behaviors reported more parent-child communication about sexual topics. These results highlight the need to begin risk prevention efforts early, prior to pubertal development. Research is needed to understand how parents can help youths better cope with pubertal development to avoid involvement in sexual and nonsexual risk behaviors.

Association of multiple behavioral risk factors with adolescents' willingness to engage in eHealth promotion.

OBJECTIVE: This study examines adolescents' willingness to use the internet and other forms of technology for health promotion purposes (i.e., "eHealth promotion" willingness) and determines if a relationship exists between adolescents' behavioral risks and their eHealth promotion willingness. METHODS: A total of 332 adolescents provided data at a routine medical check-up, including assessments of technology access, eHealth promotion willingness, and multiple behavioral risk factors for child- and adult-onset disease (body mass index, physical activity, smoking, sun protection, depression). RESULTS: The level of access to technology among the sample was high, with moderate willingness to engage in eHealth promotion. After adjusting for adolescents' access to technology, the presence of multiple behavioral risk factors was positively associated with willingness to use technology for health promotion purposes (beta =.12, p =.03). CONCLUSIONS: Adolescents with both single and multiple behavioral risk factors are in need of health promotion to prevent the onset of disease later in life. eHealth appears to be an acceptable and promising intervention approach with this population.

Adolescent medical providers' willingness to recommend genetic susceptibility testing for nicotine addiction and lung cancer risk to adolescents.

OBJECTIVE: To examine the influences of disease, lifestyle, and other factors on adolescent medical providers' willingness to recommend genetic susceptibility testing (GST). METHOD: Providers attending a national conference completed a self-report survey (n = 232) about their willingness to recommend hypothetical GSTs, differentiated by disease (nicotine addiction/lung cancer), patient lifestyle (nonsmoker/smoker), and other contextual factors. RESULTS: Compared to recommending GST unconditionally, providers were more willing to recommend GST with parental/patient consent/assent, and in the presence of a preexisting illness and substance abuse history. Compared to offering nicotine addiction GST to a nonsmoker, providers were more willing to offer this type of testing to a smoker and were more willing to offer GST for lung cancer regardless of patient lifestyle. CONCLUSIONS: Providers' willingness to recommend GSTs is sensitive to many factors. Efforts to integrate GST into adolescent preventive care likely will need to address these and other influences on provider behavior.

Suicidal ideation in American Indian/Alaska Native and White adolescents: The role of social isolation, exposure to suicide, and overweight.

Social isolation, exposure to suicide, and overweight increase suicidal ideation in adolescents, but no study to date has examined their relative significance in American Indian and Alaska Native (AI/AN) youth. Generalized estimating equations and path analyses were used to measure the significance and mediation of these variables in the suicidal ideation of 721 AI/ANs and 12,107 White adolescents. Social isolation, exposure to suicide, and overweight were risk factors for suicidal ideation in both races, and the associations among the variables of interest and suicidal ideation varied by race. Interventionists need to consider race in the prevention of suicidal ideation in AI/AN and White youth.

Investing in the health and well-being of young adults.

Contrary to popular perception, young adults-ages approximately 18-26 years-are surprisingly unhealthy. They are less healthy than adolescents, and they also show a worse health profile than those in their late 20s and 30s. The Affordable Care Act provisions to extend coverage for young adults are well known, and some states had already been pursuing similar efforts before the Affordable Care Act was enacted. These initiatives have resulted in important gains in young adults' heath care coverage. However, too little attention has been paid to the care that young adults receive once they are in the system. Given young adults' health problems, this is a critical omission. The Institute of Medicine and National Research Council recently released a report titled Investing in the Health and Well-Being of Young Adults. The report concludes that young adulthood is a critical developmental period and recommends that young adults ages 18-26 years be treated as a distinct subpopulation in policy, planning, programming, and research. The report also recommends action in three priority areas to improve health care for young adults: improving the transition from pediatric to adult medical and behavioral health care, enhancing preventive care for young adults, and developing evidence-based practices.

Blueprint for Action: Visioning Summit on the Future of the Workforce in Pediatrics.

The Federation of Pediatric Organizations engaged members of the pediatric community in an 18-month process to envision the future of the workforce in pediatrics, culminating in a Visioning Summit on the Future of the Workforce in Pediatrics. This article documents the planning process and methods used. Four working groups were based on the 4 domains that are likely to affect the future workforce: Child Health Research and Training, Diversity and Inclusion, Gender and Generations, and Pediatric Training Along the Continuum. These groups identified the issues and trends and prioritized their recommendations. Before the summit, 5 key megatrends cutting across all domains were identified:1. Aligning Education to the Emerging Health Needs of Children and Families 2. Promoting Future Support for Research Training and for Child Health Research 3. Striving Toward Mastery Within the Profession 4. Aligning and Optimizing Pediatric Practice in a Changing Health Care Delivery System 5. Taking Advantage of the Changing Demographics and Expertise of the Pediatric Workforce At the Visioning Summit, we assembled members of each of the working groups, the Federation of Pediatric Organizations Board of Directors, and several invited guests to discuss the 5 megatrends and develop the vision, solutions, and actions for each megatrend. Based on this discussion, we offer 10 recommendations for the field of pediatrics and its leading organizations to consider taking action.

Diversity and inclusion training in pediatric departments.

BACKGROUND AND OBJECTIVE: The diversifying US population of children necessitates assessing the diversity of the pediatric academic workforce and its level of cultural competency training. Such data are essential for workforce and educational policies. METHODS: An 8-question survey was sent to 131 US pediatric chairs to assess plans for diversity, targeted groups, departmental diversity, diversity measures, perceived success in diversity, and presence and type of cultural competency training. RESULTS: In all, 49.6% of chairs responded, and three-quarters of them reported having a plan for diversity, which targeted racial; ethnic; gender; lesbian, gay, bisexual, and transgender; disabled; and social class groups. Of the residents, 75% were women, as compared with 54% of faculty and 26% of chairs. Racial and ethnic diversity was limited among trainees, faculty, and leaders; <10% of each group was African American, Hispanic, or Native American. Asian Americans were more common among trainees (15%-33%) but were less common in faculty and leadership positions (0%-14%). Lesbian, gay, bisexual, and transgender physicians were represented in some groups. Measures of diversity included the number of trainees and faculty, promotion success, climate assessments, and exit interviews. Overall, 69% of chairs reported being successful in diversity efforts. A total of 90% reported cultural competency training for trainees, and 74% reported training for faculty and staff. Training in cultural competency included linguistic training, primarily in Spanish. CONCLUSIONS: Pipeline issues for minorities are ongoing challenges. Pediatric leadership needs more representation of racial and ethnic minorities, women, and LGBT. Suggestions for workforce and educational policies are made.

Fusion of cell-penetrating peptides to thermally responsive biopolymer improves tumor accumulation of p21 peptide in a mouse model of pancreatic cancer.

Current therapies for the treatment of pancreatic cancer are limited. The limitations of this type of treatment are abundant. The majority of chemotherapeutic agents used in clinics are highly toxic to both tumor cells and normal tissues due to the lack of specificity. Resistance can develop due to overexposure of these agents. To address these issues, these agents must be made more exclusive toward the tumor site. We have developed a macromolecular carrier based on the sequence of the biopolymer elastin-like polypeptide (ELP) that is able to aggregate upon reaching the externally heated tumor environment. This carrier is specific to the tumor as it only aggregates at the heated tumor site. ELP is soluble below its transition temperature but will aggregate when the temperature is raised above its transition temperature. ELP was modified by p21, a cell cycle inhibitory peptide, and the addition of Bac, a cell-penetrating peptide with nuclear localization capabilities. In this study, p21-ELP-Bac and its control, ELP-p21, were used in cell proliferation studies using the pancreatic cancer cell lines Panc-1, MiaPaca-2, and S2013. ELP-p21 had little effect on proliferation, while the half maximal inhibitory concentration of p21-ELP-Bac was ∼30 µM. As translocation across the plasma membrane is a limiting step for delivery of macromolecules, these polypeptides were utilized in a pancreatic xenograft model to study the plasma clearance, biodistribution, tumor accumulation, and tumor reduction capabilities of the polypeptide with and without a cell-penetrating peptide.

Exposure to peers who smoke moderates the association between sports participation and cigarette smoking behavior among non-white adolescents.

Adolescent sports participants are less likely to smoke cigarettes, and sports participation may prevent young people from smoking. Research suggests that the relationship between sports participation and smoking may vary by race/ethnicity and is also possibly moderated by exposure to peer smoking. We investigated these relationships in a sample of 311 adolescents ages 13-21 presenting for well-visit medical appointments. Participants completed valid assessments of demographics, sports participation, exposure to peer smoking, and smoking behavior. The primary outcome was smoking status (never smoked, tried smoking, experimental/current smoker). Ordinal logistic regression was used separately for non-Hispanic White (n=122) and non-white (n=189; 70.4% black, 14.3% Hispanic, and 15.3% other) adolescents. Among White adolescents, sports participants had significantly lower odds of smoking than non-sports participants, independent of age, gender, and peer smoking. For non-Whites, the adjusted effect of sports participation on smoking depended upon exposure to peers who smoke. Compared with non-sport participants with no exposure to peer smoking, sports participants with no exposure to peer smoking had significantly lower odds of smoking, whereas sports participants with exposure to peer smoking had significantly higher odds of smoking. Sports appear to be protective against smoking among non-Hispanic White adolescents, but among non-White adolescents exposure to peer smoking influences this protection. Interventions incorporating sports to prevent smoking should consider these racial/ethnic differences to address disparities in smoking-related disease.

Cigarette smoking among adolescents with type 1 diabetes: strategies for behavioral prevention and intervention.

Smoking is the leading preventable cause of death in the U.S. and preventing smoking initiation among adolescents is a public health priority and a central element of comprehensive tobacco control. While cigarette smoking is harmful to all youths, those with special healthcare needs are particularly vulnerable to the negative health consequences of smoking, and adolescents with type 1 diabetes (T1D) urgently stand out as a high-risk group. Available literature suggests the prevalence and risk factors for smoking among adolescents with T1D are strikingly similar to the general population. Moreover, smoking negatively affects T1D management and increases risk for and progression of adverse health outcomes related to T1D. Adolescents with T1D are also influenced by disease-related social and behavioral factors that affect decisions about smoking. Pediatric health care providers (HCPs) are optimally-positioned to screen and counsel adolescents with T1D to avoid smoking, as they have well-established relationships with young patients and regularly scheduled visits surrounding T1D management. However, several barriers inhibit HCPs from screening/counseling adolescents with T1D for smoking on a regular basis. Well-established strategies for behavioral counseling for smoking in the healthcare setting may be effective to prevent and reduce smoking among adolescents with T1D. HCPs who care for these young patients can tailor proven counseling approaches to the context of T1D to address smoking alongside other behavioral factors that are central to disease management. Empirical research is also needed to inform the development and deployment of healthcare-based interventions and maximize their impact within this population.