Lee J, Romero R, Dong Z, Xu Y, Qureshi F, Jacques S, Yoo W, Chaiworapongsa T, Mittal P, Hassan S S & Kim C J (2011) Histopathology 59, 928–938
Unexplained fetal death has a biological signature of ...maternal anti‐fetal rejection: chronic chorioamnionitis and alloimmune anti‐human leucocyte antigen antibodies
Aims: Chronic chorioamnionitis is a histological manifestation of maternal anti‐fetal cellular rejection. As failure of graft survival is the most catastrophic event in organ transplantation, we hypothesized that fetal death could be a consequence of maternal rejection. The aim of this study was to assess whether there is evidence of cellular and antibody‐mediated rejection in fetal death.
Methods and results: Placental histology was reviewed for the presence of chronic chorioamnionitis in unexplained preterm fetal death (n = 30) and preterm live birth (n = 103). Amniotic fluid CXCL10 concentrations were measured with a specific immunoassay. Chronic chorioamnionitis was more frequent in fetal death than in live birth (60.0% versus 37.9%; P < 0.05) and fetal death had a higher median amniotic fluid CXCL10 concentration than live birth (2.0 versus 1.8 ng/ml, P < 0.05), after adjusting for gestational age at amniocentesis. Maternal anti‐human leucocyte antigen class II panel‐reactive seropositivity determined by flow cytometry was higher in fetal death compared to live birth (35.7% versus 10.9%; P < 0.05).
Conclusions: Chronic chorioamnionitis is a common pathologic feature in unexplained preterm fetal death. This novel finding suggests that cellular and antibody‐mediated anti‐fetal rejection of the mother is associated with fetal death (graft failure) in human pregnancy.
Methods We conducted a meta-regression analysis of statin trials to estimate the effect of statin therapy on the risk of MCE per mmol/L change in LDL-C, high-density lipoprotein cholesterol (HDL-C) ...and triglycerides (TG).
Problem
Maternal anti‐fetal rejection is a mechanism of disease in spontaneous preterm labor. The objective of this study was to determine whether the presence of human leukocyte antigen (HLA) ...panel‐reactive antibodies (PRA) during the second trimester increases the risk of spontaneous preterm delivery.
Methods of study
This longitudinal case‐control study included pregnant women with spontaneous preterm deliveries (n = 310) and control patients with normal term pregnancies (n = 620), matched for maternal age and gravidity. Maternal plasma samples obtained at 14–16, 16–20, 20–24, and 24–28 weeks of gestation were analyzed for HLA class I and class II PRA positivity using flow cytometry. The fetal HLA genotype and maternal HLA alloantibody epitope were determined for a subset of patients with positive HLA PRA.
Results
(i) Patients with spontaneous preterm delivery were more likely to exhibit HLA class I (adjusted OR = 2.54, P < 0.0001) and class II (adjusted OR = 1.98, P = 0.002) PRA positivity than those delivering at term; (ii) HLA class I PRA positivity for patients with spontaneous preterm delivery between 28 and 34 weeks (adjusted OR = 2.88; P = 0.001) and after 34 weeks of gestation (adjusted OR = 2.53; P < 0.0001) was higher than for those delivering at term; (iii) HLA class II PRA positivity for patients with spontaneous preterm delivery after 34 weeks of gestation was higher than for those delivering at term (adjusted OR = 2.04; P = 0.002); (iv) multiparous women were at a higher risk for HLA class I PRA positivity than nulliparous women (adjusted OR = 0.097, P < 0.0001 for nulliparity); (v) nulliparous women had a higher rate of HLA class I PRA positivity with advancing gestational age (P = 0.001); and (vi) 78% of women whose fetuses were genotyped had alloantibodies specific against fetal HLA class I antigens.
Conclusion
Pregnant women with positive HLA class I or class II PRA during the second trimester are at an increased risk of spontaneous preterm delivery due to antibody‐mediated maternal anti‐fetal rejection.
To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based ...cases (n = 504) included women aged 18–74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2005. Population-based controls (n = 527) were identified through random digit dialing and matched on race and age. Eleven SNPs in 10 different genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1 Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser, GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual SNPs was seen for GSTP1 A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04–3.27 and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01–2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18–104) in black women smokers. White women smokers carrying two risk genotypes at the following loci were at increased risk of lung cancer compared with individuals not carrying risk alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1 and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of lung cancer risk in white smoking women included age, family history of lung cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the need for continued study of estrogen in relation to lung cancer risk. Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair pathways will be useful in developing more predictive models of individual risk.
Rapid growth of mobile technologies has resulted in a proliferation of lifestyle-oriented mobile phone apps. However, most do not have a theoretical framework and few have been developed using a ...community-based participatory research approach. A community academic team will develop a theory-based, culturally tailored, mobile-enabled, Web-based app-the Mobile Cancer Prevention App (mCPA)-to promote adherence to dietary and physical activity guidelines.
The aim of this study is to develop mCPA content with input from breast cancer survivors.
Members of SISTAAH (Survivors Involving Supporters to Take Action in Advancing Health) Talk (N=12), treated for Stages I-IIIc breast cancer for less than 1 year, 75 years of age or younger, and English-speaking and writing, will be recruited to participate in the study. To develop the app content, breast cancer survivors will engage with researchers in videotaped and audiotaped sessions, including (1) didactic instructions with goals for, benefits of, and strategies to enhance dietary intake and physical activity, (2) guided discussions for setting individualized goals, monitoring progress, and providing or receiving feedback, (3) experiential nutrition education through cooking demonstrations, and (4) interactive physical activity focused on walking, yoga, and strength training. Qualitative (focus group discussions and key informant interviews) and quantitative (sensory evaluation) methods will be used to evaluate the participatory process and outcomes.
Investigators and participants anticipate development of an acceptable (frequency and duration of usage) feasible (structure, ease of use, features), and accessible mobile app available for intervention testing in early 2017.
Depending on the availability of research funding, mCPA testing, which will be initiated in Miami, will be extended to Chicago, Houston, Philadelphia, and Los Angeles.
Background: Efforts aimed at health care reform and continued advances in information technologies have prompted interest among providers and researchers in patient web portals. Patient web portals ...are password-protected online websites that offer the patients 24-hour access to personal health information from anywhere with an Internet connection. Methods: This article, which is based upon bibliographic searches in PubMed, reviews important developments in web portals for primary and secondary disease prevention, including patient web portals tethered to electronic medical records, disease-specific portals, health disparities, and health-related community web portals. Results: Although findings have not been uniformly positive, several studies of the effectiveness of health care system patient portals in chronic disease management have shown promising results with regard to patient outcomes. Patient web portals have also shown promising results in increasing adherence with screening recommendations. Racial and ethnic minorities, younger persons, and patients who are less educated or have lower health literacy have been found to be less likely to use patient portals. Conclusion: Additional studies are needed of the utility and effectiveness of different elements of web portals for different patient populations. This should include additional diseases and health topics such as smoking cessation and weight management. Keywords: chronic diseases, diabetes, electronic health record, health disparities, hypertension, health information technology, immunization, patient web portals, screening
In a previous report, we demonstrated the efficacy of an educational intervention focused on increasing colorectal cancer screening rates among African Americans. Despite participating in the ...intervention, however, nearly two-thirds of participants did not seek and receive screening. Participants were African-Americans over age 49 (N = 257) who had not been screened for colorectal cancer according to guidelines. At baseline, participants completed tests measuring fatalism, perceived stress, self-esteem, attitudes/benefits/barriers, social support, and social network diversity. Those who completed the educational intervention were followed up by telephone to learn if they had been screened. We compared the scores on the psychometric tests of the participants who had been screened against the scores of those who had not. Only the mean scores on the attitudes, benefits, and barriers scale distinguished participants who had been screened from those who had not (p = 0.0816 on bivariate testing and p = 0.0276 in the logistic regression model). Social interaction among participants or social cognitive learning may have played a role in determining which participants were screened, but we were not able to demonstrate this. The major factor distinguishing participants who were not screened was their attitude toward screening at baseline. There is a subset of African Americans who are persistently resistant to screening, and their perspective in this regard must be addressed if colorectal cancer disparities are to be reduced.
...we compared the expected clinical benefit predicted by the meta-regression equation with the observed results from the meta-analysis of HDL-C raising therapies.
Summary
Background Obesity disproportionately affects African Americans (AA) (especially women), and is linked to depressed 25‐hydroxyvitamin D (25‐OH D) and elevated parathyroid hormone (PTH). The ...relationship of 25‐OH D and PTH with body composition and size in AA is not well known.
Objective To determine the relationship of 25‐OH D and PTH levels with body composition and anthropometric measures.
Design A cross‐sectional study was conducted in 98 healthy, overweight, adult AA enrolled in an NIH/NIEHS‐sponsored weight loss/salt‐sensitivity trial.
Measurements Multivariable linear regression analyses were used to explore the relationship of 25‐OH D and PTH with body composition, determined by dual‐energy X‐ray absorptiometry, and anthropometric measures. Body composition and size were contrasted across vitamin D/PTH groups using general linear models: (i) normal (25‐OH D >50 nmol/l, PTH ≤65 pg/ml), (ii) low 25‐OH D and normal PTH and (iii) low 25‐OH D and high PTH.
Results Age, gender and season‐adjusted regression analyses showed that PTH was directly correlated with total (P = 0·02), truncal (P = 0·03) and extremity (P = 0·03) fat mass, while 25‐OH D was inversely related to truncal fat mass (P = 0·02). Total fat mass in groups 1–3, respectively, was 30·0, 34·0 and 37·4 kg (P = 0·008); truncal fat mass was 13·4, 15·9 and 17·6 kg (P = 0·006) and extremity fat mass was 15·8, 16·9 and 19·7 kg (P = 0·02). Lean mass did not differ across the three groups.
Conclusions Our findings show that lower 25‐OH D and raised PTH are both correlated, though in opposite directions, with fat mass, fat distribution and anthropometric measures in adult AA.
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