Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

[Q]: Context: Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.", 'Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6x vs 1.5x, respectively at 10 muM), while fenofibrate did not induce changes in either.
Answer: These results suggest that in vivo (1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments.
[A]: Are plasma PCSK9 levels significantly modified by statins and fibrates in humans?


[Q]: Context: Brain structures underlying posttraumatic stress disorder (PTSD) have been a focus of imaging studies, but associations between treatment outcome and alterations in brain structures remain largely unexamined. We longitudinally examined the relation of structural changes in the rostral anterior cingulate cortex (rACC), a previously identified key region in the PTSD fear network, to outcome of prolonged exposure (PE) treatment.', 'The sample included 78 adults (53 women): 41 patients with PTSD and 37 trauma-exposed healthy volunteers (TE-HCs). Patients underwent a 10-week course of PE treatment and completed pre- and posttreatment assessments and magnetic resonance imaging (MRI) structural scans. TE-HCs also underwent assessment and MRI at baseline and 10 weeks later. PE remitters (n\xa0=\xa011), nonremitters (n\xa0=\xa014), and TE-HCs, were compared at baseline on demographic and clinical characteristics and ACC structure. Remitters, nonremitters, and TE-HCs were compared for pre- to posttreatment clinical and structural ACC change, controlling for potential confounding variables.', 'There were no baseline differences in structure between PTSD and TE-HCs or remitters and nonremitters. Following treatment, PTSD remitters exhibited cortical thinning and volume decrease in the left rACC compared with PTSD nonremitters and TE-HCs.
Answer: These results, while in need of replication, suggest that PE treatment for PTSD, by extinguishing maladaptive trauma associations, may promote synaptic plasticity and structure change in rACC. Future research should explore possible underlying mechanisms.
[A]: Does pTSD REMISSION AFTER PROLONGED EXPOSURE TREATMENT be ASSOCIATED WITH ANTERIOR CINGULATE CORTEX THINNING AND VOLUME REDUCTION?


[Q]: Context: Our purpose was to study the incidence and location of histologic evidence of intrauterine bleeding in preterm and term placentas.', "A total of 462 consecutive placentas delivered at < 32 weeks' gestation, from which cases of placenta previa, stillbirth, and multiple gestation were excluded, were compared with 108 consecutive term placentas (with similar exclusion criteria) in regard to the presence of hemosiderin in decidua of basal plate or placental membranes. Of the 462 preterm cases, 448 charts made specific reference to the presence or absence of vaginal bleeding. Bloody show alone was not considered bleeding. The blinded scoring of lesions (including acute ascending infection, uteroplacental vascular pathologic processes and related ischemic damage, chronic inflammation, and coagulation related lesions) was analyzed by contingency tables (p < 0.05 significant).", 'A total of 196 of 462 (43%) preterm placentas had any decidual hemosiderin compared with one of 108 (0.8%) at term (p < 0.00001). Among the preterm cases, hemosiderin was significantly more common in preeclampsia (45/76, 60%) and in cases clinically diagnosed as nonhypertensive abruptio placentae (21/33, 64%) than in premature membrane rupture (72/192, 37.5%) and preterm labor (58/161, 36%, p < 0.003). The incidence of placental lesions in preterm cases with extraplacental membrane hemosiderin was not different than it was in cases without hemosiderin. Placental lesions related to basal-plate decidual hemosiderin in the preterm cases were villous infarct (p < 0.0001), uteroplacental vessels with absence of physiologic change (p < 0.003) and increased numbers of circulating nucleated erythrocytes (p < 0.0007), uteroplacental thrombosis (p < 0.0001), and villous fibrosis (p < 0.0001) and hypovascularity (p < 0.0001). Among the preterm cases, 23 of 48 (48%) with first-trimester bleeding, 33 of 66 (50%) with second-trimester bleeding, and 31 of 64 (48%) with multiple episodes of bleeding had decidual hemosiderin (p < 0.0001). A clinical history of gestational bleeding was significantly less common in cases of preterm preeclampsia with histologic evidence of bleeding (four of 73, 5.5%) than in nonhypertensive abruptio placentae (18/31, 58%), premature rupture of membranes (52/183, 28%), or preterm labor (31/161, 19%, p < 0.0001). Hemosiderin was not related to clinical bleeding < 72 hours of delivery (p > 0.20).
Answer: Decidual bleeding is common in all clinical types of preterm birth and is most common in preterm preeclampsia and nonhypertensive abruption placentae. A clinical history of bleeding is not correlated with the presence of decidual hemosiderin. Bleeding in the basal plate is related to histologic evidence of chronic uteroplacental vascular pathologic processes, which in cases of spontaneous prematurity (premature rupture of membranes, preterm labor, nonhypertensive abruptio placentae) may be associated with decidual bleeding which occasionally may be clinically manifested as gestational bleeding.
[A]:
Is histologic evidence of old intrauterine bleeding more frequent in prematurity?