Many LINE1 elements contribute to the transcriptome of human somatic cells

Over 600 LINE 1 elements are shown to be transcribed in humans; 400 of these are full-length elements in the reference genome

Gene regulation of neurokinin B and its receptor NK3 in late pregnancy and pre-eclampsia

Elevated circulating levels of the tachykinin, neurokinin B (NKB), have been observed in women with pre-eclampsia during the third trimester of pregnancy. Currently, the molecular mechanisms responsible for these increased levels remain unknown. To understand the molecular regulation, we have compared the differences in gene expression of the tachykinins and their receptors in control and pre-eclamptic placentae and the responses of the TAC3 gene encoding NKB to proposed physiological triggers of pre-eclampsia including hypoxia and oxidative stress using real-time quantitative PCR. We have determined the placenta to be the main site of TAC3 expression with levels 2.6-fold higher than the brain. TAC3 expression was found to be significantly higher in pre-eclamptic placenta (1.7-fold, P < 0.05) than in normal controls. No evidence was found that hypoxia and oxidative stress were responsible for increases in TAC3 expression. In rat placenta, a longitudinal study in normal late pregnancy was associated with a significant down-regulation of the NKB/NK3 ligand-receptor pair (P < 0.05). The present data suggest that the increased placental expression of TAC3 is part of the mechanism leading to the increased circulating levels of NKB in pre-eclampsia

Effects of Timing on In-hospital and One-year Outcomes after TransCarotid Artery Revascularization.

OBJECTIVE: Current recommendations are to perform carotid endarterectomy (CEA) within two weeks of symptoms due to superior long-term stroke prevention, although urgent CEA within 48-hours has been associated with increased perioperative stroke. With the development and rapid adoption of TransCarotid Artery Revascularization (TCAR), we aim to study the impact of timing on outcomes after TCAR. METHODS: Symptomatic patients undergoing TCAR in the Vascular Quality Initiative between September 2016 and November 2019 were stratified by time to procedure: urgent (TCAR within 48-hours), early (TCAR between 3-14 days after symptoms), and late (TCAR greater than 14 days after symptoms). Primary outcome was in-hospital rates of stroke/death and evaluated using logistic regression. Secondary outcome was one-year rate of recurrent ipsilateral stroke and mortality, analyzed using Kaplan Meier Survival Analysis. RESULTS: A total of 2608 symptomatic patients undergoing TCAR were included: 144 urgent (5.52%), 928 early (35.58%), and 1536 (58.90%) late. Patients undergoing urgent intervention had increased risk of in-hospital stroke/death that was driven primarily by increased risk of stroke. No differences were seen in in-hospital death. On adjusted analysis, urgent intervention had a 3-fold increased odds of stroke [OR:2.8, 95%CI:1.3-6.2, p=0.01] and a 3-fold increased odds of stroke/death [OR:2.9, 95%CI:1.3-6.4, p=0.01] when compared to late intervention. Patients undergoing early intervention had comparable risks of stroke [OR:1.3, 95%CI:0.7-2.3, p=0.40] and stroke/death [OR:1.2, 9%CI:0.7-2.1, p=0.48] when compared to late intervention. On subset analysis, the type of presenting symptoms was an effect modifier. Both patients presenting with stroke and patients presenting with transient ischemic attacks (TIA) or amaurosis fugax (AF) had increased risk of stroke/death when undergoing urgent compared to late TCAR: [OR:2.7, 95%CI:1.1-6.6, p=0.04] and [OR:4.1, 95%CI:1.1-15.0, p=0.03] respectively. However only patients presenting with TIA or AF had experienced increased risk of stroke when undergoing urgent compared to late TCAR: [OR:5.0, 95%CI:1.4-17.5, p CONCLUSION: TCAR has a reduced incidence of stroke when performed 48-hours after onset of symptoms. Urgent TCAR within 48 hours of onset of stroke is associated with a three-fold increased risk of in-hospital stroke/death with no added benefit up to one year after the intervention. Further studies are needed on long-term outcomes of TCAR stratified by timing of the procedure

Effects of timing on in-hospital and one-year outcomes after transcarotid artery revascularization

ObjectiveThe current recommendations are to perform carotid endarterectomy within 2&nbsp;weeks of symptoms for maximum long-term stroke prevention, although urgent carotid endarterectomy within 48&nbsp;hours has been associated with increased perioperative stroke. With the development and rapid adoption of transcarotid artery revascularization (TCAR), we decided to study the effect of timing on the outcomes after TCAR.MethodsThe Vascular Quality Initiative database was searched for symptomatic patients who had undergone TCAR from September 2016 to November 2019. These patients were stratified by the interval to TCAR after symptom onset: urgent, within 48&nbsp;hours; early, 3 to 14&nbsp;days; and late, &gt;14&nbsp;days. The primary outcome was the in-hospital rate of combined stroke and death (stroke/death), evaluated using logistic regression analysis. The secondary outcome was the 1-year rate of recurrent ipsilateral stroke and mortality, evaluated using Kaplan-Meier survival analysis.ResultsA total of 2608 symptomatic patients who had undergone TCAR were included. The timing was urgent for 144 patients (5.52%), early for 928 patients (35.58%), and late for 1536 patients (58.90%). Patients undergoing urgent intervention had an increased risk of in-hospital stroke/death, which was driven primarily by an increased risk of stroke. No differences were seen for in-hospital death. On adjusted analysis, urgent intervention resulted in a threefold increased risk of stroke (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.3-6.2; P&nbsp;= .01) and a threefold increased risk of stroke/death (OR, 2.9; 95% CI, 1.3-6.4; P&nbsp;= .01) compared with late intervention. Patients undergoing early intervention had comparable risks of stroke (OR, 1.3; 95% CI, 0.7-2.3; P&nbsp;= .40) and stroke/death (OR, 1.2; 95% CI, 0.7-2.1; P&nbsp;= .48) compared with late intervention. On subset analysis, the type of presenting symptoms was an effect modifier. Patients presenting with stroke and those presenting with transient ischemic attack or amaurosis fugax both had an increased risk of stroke/death when undergoing urgent compared with late TCAR (OR, 2.7; 95% CI, 1.1-6.6; P&nbsp;= .04; and OR, 4.1; 95% CI, 1.1-15.0; P&nbsp;= .03, respectively). However only patients presenting with transient ischemic attack or amaurosis fugax had experienced an increased risk of stroke with urgent compared with late TCAR (OR, 5.0; 95% CI, 1.4-17.5; P&nbsp;&lt; .01). At 1&nbsp;year of follow-up, no differences were seen in the incidence of recurrent ipsilateral stroke (urgent, 0.7%; early, 0.2%; late, 0.1%; P&nbsp;= .13) or postdischarge mortality (urgent, 0.7%; early, 1.6%; late, 1.8%; P&nbsp;= .71).ConclusionsWe found that TCAR had a reduced incidence of stroke when performed 48&nbsp;hours after symptom onset. Urgent TCAR within 48&nbsp;hours of the onset of stroke was associated with a threefold increased risk of in-hospital stroke/death, with no added benefit for ≤1&nbsp;year after intervention. Further studies are needed on long-term outcomes of TCAR stratified by the timing of the procedure

The impact of age on in-hospital outcomes after transcarotid artery revascularization, transfemoral carotid artery stenting, and carotid endarterectomy.

OBJECTIVE: Previous data showed superior outcomes of carotid endarterectomy (CEA) compared with transfemoral carotid artery stenting (TFCAS) in elderly patients because of an increased stroke risk in TFCAS-treated patients. Transcarotid artery revascularization (TCAR) with flow reversal was developed to mitigate the maneuvers at highest risk for causing stroke during TFCAS, such as manipulation of a diseased aortic arch and crossing of the carotid lesion before deployment of an embolic protection device. This study aimed to compare the association between age and outcomes after TCAR, TFCAS, and CEA. METHODS: All patients undergoing carotid procedures in the Society for Vascular Surgery Vascular Quality Initiative database between 2015 and November 2018 were included. Patients were divided into three different age groups (≤70 years, 71-79 years, and ≥80 years). In-hospital outcomes after TCAR vs TFCAS and after TCAR vs CEA were compared in each age group by introducing an interaction term between treatment type and age in the logistic regression analysis after adjustment for patients\u27 preoperative characteristics. RESULTS: The study cohort included 3152 TCAR, 10,381 TFCAS, and 61,650 CEA cases. The absolute and adjusted in-hospital outcomes after TCAR did not change across the different age groups. The rates of in-hospital stroke/death after TCAR were 1.4% in patients ≤70 years vs 1.9% in patients 71 to 79 years and 1.5% in patients ≥80 years (P = .55). Comparison of TCAR to CEA across different age groups showed no significant differences in outcomes, and no interaction was noted between treatment and age in predicting in-hospital stroke/death (P = .80). In contrast, TCAR was associated with a 72% reduction in stroke risk (4.7% vs 1%; odds ratio [OR], 0.28; 95% confidence interval [CI], 0.12-0.65; P \u3c .01), 65% reduction in risk of stroke/death (4.6% vs 1.5%; OR, 0.35; 95% CI, 0.20-0.62; P \u3c .001), and 76% reduction in the risk of stroke/death/myocardial infarction (5.3% vs 2.5%; OR, 0.24; 95% CI, 0.12-0.47; P \u3c .001) compared with TFCAS in patients ≥80 years. Moreover, compared with TCAR, the odds of stroke/death after TFCAS doubled at 77 years (OR, 2.0; 95% CI, 1.4-3.0; P \u3c .01) and tripled at 90 years (OR, 3.0; 95% CI, 1.6-5.8; P \u3c .01; P value for the interaction = .08). CONCLUSIONS: TCAR is a relatively safe procedure regardless of the patient\u27s age. The advantages of TCAR become more pronounced in elderly patients, with significant reductions in in-hospital stroke compared with TFCAS in patients ≥77 years old, independent of symptomatic status and other medical comorbidities. These findings suggest that TCAR should be preferred to TFCAS in elderly patients who are at high surgical risk

In-Hospital Outcomes of Urgent, Early, or Late Revascularization for Symptomatic Carotid Artery Stenosis

Background and purposeAdvancements in carotid revascularization have produced promising outcomes in patients with symptomatic carotid artery stenosis. However, the optimal timing of revascularization procedures after symptomatic presentation remains unclear. The purpose of this study is to compare in-hospital outcomes of transcarotid artery revascularization (TCAR), transfemoral carotid stenting (TFCAS), or carotid endarterectomy (CEA) performed within different time intervals after most recent symptoms.MethodsThis is a retrospective cohort study of United States patients in the vascular quality initiative. All carotid revascularizations performed for symptomatic carotid artery stenosis between September 2016 and November 2019 were included. Procedures were categorized as urgent (0-2 days after most recent symptom), early (3-14 days), or late (15-180 days). The primary outcome of interest was in-hospital stroke and death. Secondary outcomes include in-hospital stroke, death, and transient ischemic attacks. Multivariable logistic regression was used to compare outcomes.ResultsA total of 18 643 revascularizations were included: 2006 (10.8%) urgent, 7423 (39.8%) early, and 9214 (49.42%) late. Patients with TFCAS had the highest rates of stroke/death at all timing cohorts (urgent: 4.0% CEA, 6.9% TFCAS, 6.5% TCAR, P=0.018; early: 2.5% CEA, 3.8% TFCAS, 2.9% TCAR, P=0.054; late: 1.6% CEA, 2.8% TFCAS, 2.3% TCAR, P=0.003). TFCAS also had increased odds of in-hospital stroke/death compared with CEA in all 3 groups (urgent adjusted odds ratio [aOR], 1.7 [95% CI, 1.0-2.9] P=0.03; early aOR, 1.6 [95% CI, 1.1-2.4] P=0.01; and late aOR, 1.9 [95% CI, 1.2-3.0] P=0.01). TCAR and CEA had comparable odds of in-hospital stroke/death in all 3 groups (urgent aOR, 1.9 [95% CI, 0.9-4], P=0.10), (early aOR, 1.1 [95% CI, 0.7-1.7], P=0.66), (late aOR, 1.5 [95% CI, 0.9-2.3], P=0.08).ConclusionsCEA remains the safest method of revascularization within the urgent period. Among revascularization performed outside of the 48 hours, TCAR and CEA have comparable outcomes

Identification by subtractive hybridization of a spectrum of novel and unexpected genes associated with in vitro differentiation of human cytotrophoblast cells

We have previously demonstrated that epidermal growth factor (EGF), colony stimulating factor-1 (CSF-I), and granulocyte-monocyte colony stimulating factor (GMCSF) stimulate, while transforming growth factor beta 1 (TGF beta 1) inhibits, cytotrophoblast differentiation. To identify genes mediating EGF induced differentiation, we constructed a subtracted cDNA library between undifferentiated cytotrophoblast and differentiating cytotrophoblast. We identified six novel genes and four known syncytial products alpha-human chorionic gonadotrophin (alpha hCG) pregnancy-specific beta 1-glycoprotein, 3 beta-hydroxysteroid dehydrogenase, and plasminogen activator inhibitor type 1 whose mRNAs increased during differentiation. Ten other genes were identified whose mRNAs increased during differentiation. Five of these (keratin 19, calcreticulin, heat shock protein 27, serum and glucocorticoid-regulated kinase and adrenomedullin) were not previously reported to be expressed in placenta. Five other genes known to be expressed in placenta were identified. keratin 8, fibronectin, mitochondrial ATP synthase, 1119, and cytosolic copper-zinc superoxide dismutase (SOD-1). Several of these genes may have regulatory functions in trophoblast differentiation