Prolonged exposure to lower LDL-C beginning early in life is associated with a substantially greater reduction in the risk of CHD than the current practice of lowering LDL-C beginning later in life.

Acute chorioamnionitis (ACA) is a well-established lesion of the placenta in cases with intra-amniotic infection. In contrast, the clinicopathologic significance of chronic chorioamnionitis (CCA) is unclear. This study was conducted to determine the frequency and severity of CCA in normal pregnancy and various pregnancy complications. Placentas from the following patient groups were studied: 1) term not in labor (TNL; n=100), 2) term in labor (TIL; n=100), 3) preterm labor (PTL; n=100), 4) preterm prelabor rupture of the membranes (PPROM; n=100), 5) preeclampsia at term (TPE; n=100), 6) preterm preeclampsia (PPE; n=100), and 7) small-for-gestational-age at term (SGA; n=100). Amniotic fluid CXCL10 concentration was measured in 64 patients. CXCL9, CXCL10, and CXCL11 mRNA expressions in the chorioamniotic membranes were assessed by real-time quantitative RT-PCR. The frequency of CCA in PTL and PPROM groups was 34% and 39%, respectively, which was higher than those of normal term placentas (TNL 19%, TIL 8%; p<0.05 each). The frequency of CCA in TPE, PPE and SGA groups was 23%, 16%, and 13%, respectively. Concomitant villitis of unknown etiology (VUE) was found in 38.2% and 35.9% of PTL and PPROM cases with CCA, respectively. Interestingly, the median gestational age of preterm CCA cases was higher than that of ACA cases (p<0.05). The median amniotic fluid CXCL10 concentration was higher in cases with CCA than in those without, in both PTL and PPROM groups (p<0.05 and p<0.01, respectively). CXCL9, CXCL10, and CXCL11 mRNA expression in the chorioamniotic membranes was also higher in CCA cases than in those without CCA (p<0.05). We propose that CCA defines a common placental pathologic lesion among the PTL and PPROM groups, especially in cases of late preterm birth. Its association with VUE and the chemokine profile in amniotic fluid suggests an immunological origin, akin to transplantation rejection and graft-versus-host disease in the chorioamniotic membranes.

BackgroundChronic chorioamnionitis is found in more than one-third of spontaneous preterm births. Chronic chorioamnionitis and villitis of unknown etiology represent maternal anti-fetal cellular rejection. Antibody-mediated rejection is another type of transplantation rejection. We investigated whether there was evidence for antibody-mediated rejection against the fetus in spontaneous preterm birth.Methods and FindingsThis cross-sectional study included women with (1) normal pregnancy and term delivery (n = 140) and (2) spontaneous preterm delivery (n = 140). We analyzed maternal and fetal sera for panel-reactive anti-HLA class I and class II antibodies, and determined C4d deposition on umbilical vein endothelium by immunohistochemistry. Maternal anti-HLA class I seropositivity in spontaneous preterm births was higher than in normal term births (48.6% vs. 32.1%, p = 0.005). Chronic chorioamnionitis was associated with a higher maternal anti-HLA class I seropositivity (p<0.01), significant in preterm and term birth. Villitis of unknown etiology was associated with increased maternal and fetal anti-HLA class I and II seropositivity (p<0.05, for each). Fetal anti-HLA seropositivity was closely related to maternal anti-HLA seropositivity in both groups (p<0.01, for each). C4d deposition on umbilical vein endothelium was more frequent in preterm labor than term labor (77.1% vs. 11.4%, p<0.001). Logistic regression analysis revealed that chronic chorioamnionitis (OR = 6.10, 95% CI 1.29–28.83), maternal anti-HLA class I seropositivity (OR = 5.90, 95% CI 1.60–21.83), and C4d deposition on umbilical vein endothelium (OR = 36.19, 95% CI 11.42–114.66) were associated with preterm labor and delivery.ConclusionsA major subset of spontaneous preterm births has a signature of maternal anti-fetal cellular and antibody-mediated rejections with links to fetal graft-versus-host disease and alloimmune reactions.

Background Emerging evidence suggests that ‘adaptive’ induction of autophagy (the cellular process responsible for the degradation and recycling of proteins and organelles) may confer a cardioprotective phenotype and represent a novel strategy to limit ischemia-reperfusion injury. Our aim was to test this paradigm in a clinically relevant, large animal model of acute myocardial infarction. Methods and Results Anesthetized pigs underwent 45 min of coronary artery occlusion and 3 hours of reperfusion. In the first component of the study, pigs received chloramphenicol succinate (CAPS: an agent that purportedly up-regulates autophagy; 20 mg/kg) or saline at 10 min before ischemia. Infarct size was delineated by tetrazolium staining and expressed as a % of the at-risk myocardium. In separate animals, myocardial samples were harvested at baseline and 10 min following CAPS treatment and assayed (by immunoblotting) for two proteins involved in autophagomsome formation: Beclin-1 and light chain (LC) 3B-II. To investigate whether the efficacy of CAPS was maintained with ‘delayed’ treatment, additional pigs received CAPS (20 mg/kg) at 30 min post-occlusion. Expression of Beclin-1 and LC3B-II, as well as infarct size, were assessed at end-reperfusion. CAPS was cardioprotective: infarct size was 25±5% and 41±4% in the CAPS-pretreated and CAPS-delayed treatment groups versus 56±5% in saline-controls (p<0.01 and p<0.05 versus control). Moreover, administration of CAPS was associated with increased expression of both proteins. Conclusion Our results demonstrate attenuation of ischemia-reperfusion injury with CAPS, and are consistent with the concept that induction of autophagy may provide a novel strategy to confer cardioprotection.

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BackgroundAlthough black women experienced greater cervical cancer incidence and mortality rate reduction in recent years, they continue to have higher incidence rates than whites. Great variations also exist among geographic regions of the US, with the South having both the highest incidence and mortality rates compared to other regions. The present study explores the question of whether living in the South is associated with greater racial disparity in cervical cancer incidence and mortality by examining race- and region-specific rates and the trend between 2000 and 2012.MethodsThe Surveillance, Epidemiology, and End Results (SEER) 18 Program data was used. Cervical cancer incidence and mortality rates, annual percent changes, and disparity ratios were calculated using SEER*Stat software and Joinpoint regression for four groups: US14-Non-Hispanic White (NHW), US14-Non-Hispanic Black (NHB), South-NHW, and South-NHB, where South included 4 registries from Georgia and Louisiana and US14 were 14 US registries except the four South registries.ResultsThe average age-adjusted cervical cancer incidence rate was the highest among South-NHBs (11.1) and mortality rate was the highest among US14-NHBs (5.4). In 2012, the degree of racial disparities between South-NHBs and South-NHWs was greater in terms of mortality rates (NHB:NHW = 1.80:1.35) than incidence rates (NHB:NHW = 1.45:1.15). While mortality disparity ratios decreased from 2000–2012 for US14-NHB (APC: -1.9(-2.3,-1.4), mortality disparity ratios for South-NHWs (although lower than NHBs) increased compared to US14-NHW. Incidence rates for NHBs continued to increase with increasing age, whereas rates for NHWs decreased after age 40. Mortality rates for NHBs dramatically increased at age 65 compared to a relatively stable trend for NHWs. The increasing racial disparity with increasing age in terms of cervical cancer incidence rates became more pronounced when corrected for hysterectomy prevalence.ConclusionsBlack race and South region were associated with higher cervical cancer incidence and mortality. Cervical cancer rates uncorrected for hysterectomy may underestimate regional and racial disparities. Increasing incidence rates for older NHBs compared to NHWs warrant further research to determine whether screening should continue for NHBs over age 65.

Background Myeloproliferative neoplasm (MPN) patients often report high symptom burden that persists despite the best available pharmacologic therapy. Meditation has gained popularity in recent decades as a way to manage cancer patient symptoms. Objective The aim of this study was to examine the feasibility of 2 different consumer-based meditation smartphone apps in MPN patients and to examine the limited efficacy of smartphone-based meditation on symptoms compared with an educational control group. Methods Patients (n=128) were recruited nationally through organizational partners and social media. Eligible and consented patients were enrolled into 1 of 4 groups, 2 of which received varying orders of 2 consumer-based apps (10% Happier and Calm ) and 2 that received one of the apps alone for the second 4 weeks of the 8-week intervention after an educational control condition. Participants were asked to perform 10 min of meditation per day irrespective of the app and the order in which they received the apps. Feasibility outcomes were measured at weeks 5 and 9 with a Web-based survey. Feasibility outcomes were acceptability, demand, and limited efficacy for depression, anxiety, pain intensity, sleep disturbance, sexual function, quality of life, global health, and total symptom burden. Results A total of 128 patients were enrolled across all 4 groups, with 73.4% (94/128) patients completing the intervention. Of the participants who completed the 10% Happier app, 61% (46/76) enjoyed it, 66% (50/76) were satisfied with the content, and 77% (59/76) would recommend to others. Of those who completed the Calm app, 83% (56/68) enjoyed it, 84% (57/68) were satisfied with the content, and 97% (66/68) would recommend to others. Of those who completed the educational control, 91% (56/61) read it, 87% (53/61) enjoyed it, and 71% (43/61) learned something. Participants who completed the 10% Happier app averaged 31 (SD 33) min/week; patients completing the Calm app averaged 71 (SD 74) min/week. 10% Happier app participants saw small effects on anxiety ( P <.001 d =−0.43), depression ( P =.02; d =−0.38), sleep disturbance ( P =.01; d =−0.40), total symptom burden ( P =.13; d =−0.27), and fatigue ( P =.06; d =−0.30), and moderate effects on physical health ( P <.001; d =0.52). Calm app participants saw small effects on anxiety ( P =.29; d =−0.22...