Increased inferior vena cava wall thickness as a sign of extensive venous inflammation in Behçet's Disease.

INTRODUCTION/OBJECTIVES: Behçet's disease (BD) affects both arterial and venous vessels. We have previously shown that common femoral vein wall thickness (WT) is increased in BD and can be used as a diagnostic test. However, there is limited data assessing large veins. Therefore, this study seeks to assess inferior vena cava wall thickness (IVC) by transthoracic echocardiography (TTE) in BD compared to healthy controls (HC). METHODS: Age- and gender-matched 70 BD patients and 51 HC were included. IVC wall thickness and common femoral vein WT were measured by TTE and Doppler ultrasonography, respectively. All examinations were performed on the same day as the clinical assessment. RESULTS: The mean IVC wall thickness of BD patients was significantly higher than HC (2.9 mm (0.3) vs 2.6 mm (0.3), p < 0.001). Patients with mucocutaneous involvement (2.8 mm (0.3)) and major organ involvement (2.9 mm (0.3)) had significantly thicker walls compared to HC (p = 0.003, p < 0.001, respectively). IVC wall thickness was higher in patients with vascular involvement compared to those with nonvascular major organ involvement (3.1 mm (0.3) vs 2.8 mm (0.2), p = 0.04). There was a moderate correlation between IVC and common femoral vein WT (r = 0.49 for the right, r = 0.43 for the left, p = 0.01 for both). CONCLUSION: This study shows that venous wall inflammation is not limited to lower extremity veins and is also present in IVC walls of BD patients regardless of IVC involvement. Vascular wall inflammation is probably a widespread vascular event of all venous walls in BD. Key Points • Venous wall inflammation is not limited to lower extremity veins and is present also in IVC wall in Behçet's disease. • Extensive venous wall inflammation in Behçet's disease includes large venous structures despite not being clinically involved.

Evaluation of Arterial Stiffness Parameters and the Growth Differentiation Factor-15 Level in Patients with Premature Myocardial Infarction.

BACKGROUND: Myocardial infarction (MI) is increasing at a younger age. Growth differentiation factor-15 (GDF-15) has been implicated in several key mechanisms of atherogenesis. Arterial stiffness parameters, including pulse wave velocity (PWV) and the augmentation index (AIx), can indicate the presence or progression of atherosclerosis. The aim of this study is to evaluate the GDF-15 level and arterial stiffness parameters in patients with premature MI. METHOD: Thirty patients aged ≤45 years (mean age: 39 ± 5 years, 23 male) who recovered from a MI and 15 age and sex-matched subjects were consecutively included. The serum GDF-15 concentration levels and arterial stiffness parameters of the patients and controls were measured. RESULTS: GDF-15 levels were significantly higher in patients with premature MI, while there were no significant differences in PWV and AIx between the groups. The GDF-15 level was correlated negatively with high-density lipoprotein (HDL) cholesterol and positively with uric acid levels. Both GDF-15 (p = 0.046, odds ratio: 1.092, 95% confidence interval: 1.003-1.196) and HDL cholesterol (p = 0.037, odds ratio: 0.925, 95% confidence interval: 0.859-0.995) were found as independent factors associated with premature MI. CONCLUSIONS: GDF-15 could be a risk factor for premature MI. Further studies are needed to elucidate the central role of GDF-15 in the pathophysiology of early atherosclerosis and MI in the young population.

Evaluation of Arterial Stiffness and Subfoveal Choroidal Thickness in Patients with Coronary Slow Flow.

Background: Coronary slow flow may not only affect the coronary arteries, but it may also be a vascular problem affecting the rest of the arterial system. Objective: The aim of this study was to determine peripheral arterial stiffness and the thickness of the choroid layer in patients with slow coronary flow. Methods: Fifty consecutive patients (age, 54.3 ± 11.4 years, 38 male) with coronary slow flow and 25 consecutive patients (age, 50.5 ± 9.9 years, 16 male) with normal coronary arteries both documented by coronary angiography were included. Arterial stiffness parameters were measured noninvasively using a Mobil-O-Graph arteriography system. The choroidal thickness was assessed using the enhanced depth imaging optical coherence tomography method. Results: The patients with coronary slow flow had significantly higher peripheral systolic blood pressure, peripheral pulse pressure, central pulse pressure, and pulse wave velocity (PWV) and significantly thinner choroidal thickness compared to the controls. Thrombolysis in myocardial infarction frame count was positively correlated with PWV (r: 0.237, p = 0.041) and negatively correlated with choroidal thickness (r: -0.249, p = 0.031). There was also a negative correlation between PWV and mean choroidal thickness (r: -0.565, p < 0.001). Linear regression analysis showed that coronary slow flow was an independent predictor of both PWV and choroidal thickness when adjusted by age and sex. Conclusions: The acceleration of average peripheral arterial PWV with a thinning of choroidal thickness in patients with coronary slow flow may support the idea that this phenomenon may be a coronary presentation of a systemic microvascular disorder.

"Main Vessel-Oriented" Treatment Strategy Versus "Open Side Branch" Treatment Strategy in Acute Coronary Syndrome Patients With Culprit Bifurcation Lesions.

Percutaneous coronary intervention of bifurcation lesions is associated with an increased risk of complications in patients with acute coronary syndrome (ACS). The study aimed to evaluate the in-hospital outcomes of patients with ACS with culprit bifurcation lesions who were treated with either a "main vessel-oriented" (MVO) treatment strategy or an "open side branch" (OSB) treatment strategy. This retrospective study included 575 consecutive patients with ACS. "MVO" and "OSB" treatment strategies were defined as primary/urgent percutaneous coronary intervention procedures performed by either totally ignoring the side branch (SB) or trying to maintain both main vessel and SB open with thrombolysis in myocardial infarction 3 flow. Procedural success and major cardiac/cerebrovascular events during hospitalization were noted. MVO and OSB treatment strategies were performed on 384 and 191 patients, respectively. The procedural success rate was significantly higher in the OSB treatment strategy whereas major cardiac/cerebrovascular events rates were similar except for the contrast-induced nephropathy rate being slightly higher in OSB treatment strategy. Subgroup analysis revealed a significantly higher procedural success rate in OSB treatment strategy if the SB was located within the bifurcation core, especially in those where the diameter of SB was ≥2 mm. In conclusion, our results suggest a better procedural result with SB protection attempts in patients with ACS with a culprit bifurcation lesion if the SB is originating within the bifurcation core and its diameter is ≥2 mm. MVO treatment strategy may be preferred in most cases with minor SBs located distant to the bifurcation core because of the similar procedural success.

Programmable, Structure-Switching RhoBAST for Hybridization-Mediated mRNA Imaging in Living Cells.

The development of fluorescent probes for visualizing endogenous RNAs in living cells is crucial to understand their complex biochemical roles. Recently, we developed RhoBAST, one of the most photostable and brightest fluorescence light-up aptamers (FLAPs), as a genetically encoded tag for imaging messenger RNAs (mRNAs). Here, we describe programmable RhoBAST sequences flanked by target-binding hybridization arms that light up only when bound to the untagged target RNA in trans. As part of the hybridization arm, we introduced a modular transducer sequence that switches the secondary structure of RhoBAST and renders it incapable of binding to its fluorogenic ligand TMR-DN. Only the specific binding of the hybridization arms to the target RNA triggers the correct folding of RhoBAST and fluorescence light-up after binding to TMR-DN. We characterized the structural switching of programmable RhoBAST sequences extensively in vitro and applied them to visualize untagged mRNAs in live bacteria.

Fast-exchanging spirocyclic rhodamine probes for aptamer-based super-resolution RNA imaging.

Live-cell RNA imaging with high spatial and temporal resolution remains a major challenge. Here we report the development of RhoBAST:SpyRho, a fluorescent light-up aptamer (FLAP) system ideally suited for visualizing RNAs in live or fixed cells with various advanced fluorescence microscopy modalities. Overcoming problems associated with low cell permeability, brightness, fluorogenicity, and signal-to-background ratio of previous fluorophores, we design a novel probe, SpyRho (Spirocyclic Rhodamine), which tightly binds to the RhoBAST aptamer. High brightness and fluorogenicity is achieved by shifting the equilibrium between spirolactam and quinoid. With its high affinity and fast ligand exchange, RhoBAST:SpyRho is a superb system for both super-resolution SMLM and STED imaging. Its excellent performance in SMLM and the first reported super-resolved STED images of specifically labeled RNA in live mammalian cells represent significant advances over other FLAPs. The versatility of RhoBAST:SpyRho is further demonstrated by imaging endogenous chromosomal loci and proteins.

The Impact of Cystic Fibrosis- and Noncystic Fibrosis-Bronchiectasis on Pulmonary Artery Wall Thickness and Right Heart Functions Assessed by Speckle-Tracking Echocardiography.

BACKGROUND: Right heart functions are affected in patients with bronchiectasis as a result of pulmonary hypertension induced by chronic hypoxemia. Pulmonary artery wall thickness has recently been introduced as a sign of intensive and prolonged inflammation. The aim of this study was to analyze right ventricular and right atrial functions and to mea-sure pulmonary artery wall thickness in patients with cystic fibrosis-bronch iecta sis in comparison to those with noncystic fibrosis-bronchiectasis and healthy individuals. METHODS: We studied 36 patients with cystic fibrosis-bronchiectasis, 34 patients with noncystic fibrosis-bronchiectasis, and 32 age- and sex-matched control subjects. Lung function tests were performed. All subjects underwent comprehensive echocardiographic evaluation including conventional, tissue Doppler, speckle-tracking, and pulmonary artery wall thickness measurements. RESULTS: Right ventricular global longitudinal strain and global longitudinal right atrial strain during ventricular systole decreased in cystic fibrosis-bronchiectasis group compared with noncystic fibrosis-bronchiectasis and control groups (P <.001, both). Conversely, pulmonary artery wall thickness was increased in cystic fibrosis-bronchiectasis group in comparison to other groups (P <.001). Moreover, right ventricular global longitudinal strain was lower and pulmonary artery wall thickness was higher in patients with airflow obstruction (P <.001 and P =.025, respectively) than in those without. Only right ventricular global longitudinal strain was significantly correlated with pulmonary function test parameters. The negative effect of cystic fibrosis on right ventricular and right atrial functions was independent of age, gender, and disease duration. CONCLUSION: Our study showed that right ventricular and right atrial functions were deteriorated and pulmonary artery wall was thickened in cystic fibrosis-bronchiectasis patients more than noncystic fibrosis-bronchiectasis patients. Right ventricular global longitudinal strain detected subclinical right ventricular dysfunction and was associated with the severity of pulmonary disease.

Avidity-based bright and photostable light-up aptamers for single-molecule mRNA imaging.

Fluorescent light-up aptamers (FLAPs) have emerged as valuable tools to visualize RNAs, but are mostly limited by their poor brightness, low photostability, and high fluorescence background in live cells. Exploiting the avidity concept, here we present two of the brightest FLAPs with the strongest aptamer-dye interaction, high fluorogenicity, and remarkable photostability. They consist of dimeric fluorophore-binding aptamers (biRhoBAST and biSiRA) embedded in an RNA scaffold and their bivalent fluorophore ligands (bivalent tetramethylrhodamine TMR2 and silicon rhodamine SiR2). Red fluorescent biRhoBAST-TMR2 and near-infrared fluorescent biSiRA-SiR2 are orthogonal to each other, facilitating simultaneous visualization of two different RNA species in live cells. One copy of biRhoBAST allows for simple and robust mRNA imaging with strikingly higher signal-to-background ratios than other FLAPs. Moreover, eight biRhoBAST repeats enable single-molecule mRNA imaging and tracking with minimal perturbation of their localization, translation, and degradation, demonstrating the potential of avidity-enhanced FLAPs for imaging RNA dynamics.

Pulmonary arterial wall thickness increased in Behçet's disease patients with major organ involvement: Is it a sign of severity?

OBJECTIVES: Behçet's disease (BD) is a unique systemic vasculitis mainly involving veins, in contrast to other vasculitides. Prior studies have shown that pulmonary arteries (PAs) have a similar structure to systemic veins. In this study we aimed to assess PA wall thickness by transthoracic echocardiography (TTE) in BD patients compared with healthy controls (HCs) and patients with non-inflammatory pulmonary embolism (NIPE). METHODS: Patients with BD (n = 77) and NIPE (n = 33) and HCs (n = 57) were studied. PA wall thickness was measured from the mid-portion of the main PA with TTE by two cardiologists blinded to cases. RESULTS: PA wall thickness was significantly lower in HCs [3.6 mm (s.d. 0.3)] compared with NIPE [4.4 mm (s.d. 0.5)] and BD [4.4 mm (s.d. 0.6)] (P < 0.001 for both). PA wall thickness was similar between BD and NIPE (P = 0.6). Among patients with BD, PA wall thickness was significantly higher in patients with major organ involvement compared with mucocutaneous limited disease [4.7 mm (s.d. 0.4) vs 3.7 (0.4), P < 0.001], HCs and NIPE (P < 0.001 and P = 0.006, respectively). PA wall thickness was comparable between patients with vascular and non-vascular major organ involvement [4.6 mm (s.d. 0.5) vs 4.7 (0.3), P = 0.3]. CONCLUSION: We observed that PA wall thickness was significantly higher in BD with major organ involvement compared with patients with only mucocutaneous limited disease, HCs and NIPE. These results suggest that increased PA wall thickness may be a sign of severe disease with major organ involvement in BD.

Neurogenic stunned myocardium in acute ischemic stroke.

BACKGROUND AND PURPOSE: Neurogenic myocardial injury occurs as a result of dysregulation of autonomic nervous system. The aim of this study was to explore the frequency of elevated troponin and dynamic ST segment/T wave changes and their relation with left ventricular (LV) systolic functions in acute ischemic stroke patients. METHODS: One hundred and twenty-five patients (mean age: 65.1±15.2years, 76 male) presenting with acute ischemic stroke were consecutively included. 12-lead electrocardiogram was taken to assess dynamic ST segment/T wave changes, conventional transthoracic echocardiography to determine LV ejection fraction (LVEF). High-sensitive cardiac troponin I (hs-cTnI) level>0.04ng/mL was accepted as elevated. RESULTS: Twenty-seven patients (21.6%) had elevated hs-cTnI and 60 patients (48%) had dynamic ST segment/T wave changes. The stroke patients with elevated hs-cTnI had significantly higher NT-proBNP values (2302±3450pg/mL vs 799±2075pg/mL p<0.001) and higher frequency of ST segment/T wave changes (85.2% vs 37.8% p<0.001), and lower LVEF (52.2±13.6% vs 61.0±8.5% p=0.002) compared to patients with normal troponin levels. The patients with ST segment/T wave changes had significantly higher frequencies of hyper-lipidemia (31.7% vs 15.4% p=0.031) and coronary artery disease (CAD) (43.3% vs 13.8% p<0.001), hs-cTnI (0.19±0.55ng/mL vs 0.02±0.01ng/mL p<0.001) and NT-proBNP levels (1430±2564pg/mL vs 842±2425pg/mL p=0.016), and lower LVEF (56.1±11.7% vs 61.9±8.3% p=0.009). Linear regression analysis revealed presence of CAD, but not ST segment/T wave changes as an independent predictor of hs-cTnI (p=0.034). LVEF was independently associated with hs-cTnI (p=0.003) and presence of CAD (p=0.009) when adjusted by age, sex and presence of ST segment/T wave changes. CONCLUSION: Troponin elevation and ST segment/T wave changes occurring in patients suffering acute ischemic stroke, especially in those with CAD, may be a sign of neurogenic stunned myocardium.

Is there any relation between arterial stiffness and insomnia? A challenging question.

PURPOSE: Insomnia is a common sleep disorder which has high comorbidity with a number of cardiovascular diseases (CVD). As a possible risk factor for the CVDs, arterial stiffness may be assessed non-invasively by pulse wave velocity (PWV) and augmentation index (AI). The aim of this study was to evaluate any relation between insomnia and arterial stiffness. METHODS: Patients with insomnia were included in the study after the exclusion of other sleep disorders by polysomnography. Sleep quality and the degree of insomnia symptoms were evaluated by the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI), respectively. PWV and AI were assessed by Mobil-O-Graph arteriograph system. RESULTS: Consecutive patients with insomnia (n = 72, 56 women, mean age 55.8 ± 9.1 years) were included. Patients were grouped as those with severe ISI scores (22-28) and those with mild to moderate ISI scores (8-21). Despite no significant difference in characteristics and clinical data, patients with severe ISI scores had significantly higher total PSQI scores and NREM-2 with significantly lower REM duration. They also had significantly higher systolic blood pressure, mean blood pressure, pulse pressure, PWV, and AI compared to patients with mild and moderate ISI scores. Correlation analysis revealed that PWV and AI were significantly correlated with the ISI score and PSQI score. CONCLUSION: There is a close relation between arterial stiffness and insomnia suggesting a risk for CVD in patients with insomnia.

Myocardial involvement in Behçet's disease may be higher in patients with Neuro-Behçet's disease: a speckle tracking echocardiographic study.

BACKGROUND: Behcet's disease (BD) may present with life threating complications including neurological and cardiovascular involvement. Neuro-Behcet's disease (NBD) is one of the most important causes of morbidity and mortality in patients with BD. The aim of the present study is to investigate whether patients with NBD are different than BD patients with other manifestations in terms of subclinical myocardial dysfunction. METHODS: Forty patients with NBD (23 female, mean age: 42.4 ± 9.4 years), 40 patients with BD (9 female, mean age: 39.7 ± 9.0 years) and 40 controls (20 male, mean age: 41.8 ± 6.5 years) were consecutively included in the study. All subjects underwent a transthoracic echocardiography for evaluation of left ventricular (LV) and atrial (LA) functions with two-dimensional (2D) speckle tracking echocardiography (STE). RESULTS: Baseline characteristics, clinical data, LV dimensions, systolic and diastolic functions were all in normal range among the groups. LV global longitudinal strain (LV-GLS) was significantly lower in patients with NBD and BD patients without neurologic involvement compared to controls. LA conduit strain was significantly lower in patients with NBD compared to controls. Patients with both parenchymal NBD and vascular NBD manifestations had significantly lower LV-GLS and LA conduit strain compared to controls. Linear regression analysis demonstrated that among cardiovascular risk factors only presence of NBD was the independent predictor of LV-GLS. CONCLUSIONS: BD is associated with impaired LV and LA functions. LV-GLS and LA conduit strains of the patients with NBD were lower. NBD was an independent predictor of LV-GLS, suggesting a link between neurological manifestations and cardiac dysfunction in BD patients.

Bleeding risk with concomitant use of tirofiban and third-generation P2Y12 receptor antagonists in patients with acute myocardial infarction: A real-life data.

OBJECTIVE: Combination of dual antiplatelet therapy (DAPT) with glycoprotein (GP) IIb/IIIa inhibitors can increase bleeding risk. In this study, we aimed to investigate bleeding complications of different DAPTs with concomitant tirofiban use in patients with acute coronary syndrome (ACS). METHODS: This retrospective study included 224 consecutive ACS patients (mean age 56.6±11.1 years, 193 men) who were given conventional dose of tirofiban (25 µg/kg per 3 minutes followed by an infusion of 0.15 µg/kg/min for 24 hours) in addition to DAPT (300 mg aspirin followed by 100 mg/day + 600 mg clopidogrel followed by 75 mg/day or 180 mg ticagrelor followed by 90 mg twice daily or 60 mg prasugrel followed by 10 mg/day). Any intra-hospital bleeding complications were noted. RESULTS: Of the 224 patients, 115 were given ticagrelor and 32 were given prasugrel. Mean hemoglobin fall was similar between the patients taking ticagrelor/prasugrel and those taking clopidogrel. Ten patients taking ticagrelor and one patient taking prasugrel had hemoglobin fall ≥3 g/dL versus two patients in clopidogrel group (p=0.228). Gastrointestinal bleeding (two patients taking ticagrelor), hematoma at access site (three patients taking ticagrelor), and cardiac tamponade (two patients taking ticagrelor) rates were also similar. Creatinine levels were associated with hemoglobin fall ≥3 g/dL (p=0.032, Odds ratio 2.189, 95% confidence interval 1.070-4.479). There was no relation between hemoglobin fall ≥3 g/dL and antiplatelet agent, age, sex, hypertension, or diabetes. CONCLUSION: Tirofiban may be given to patients receiving ticagrelor or prasugrel with a bleeding rate similar to clopidogrel. Close monitoring for bleeding risk is recommended, especially in patients with higher creatinine levels.

Predictors of Concomitant Coronary Artery Disease and Major Cardiovascular Events in Patients with Acute Ischemic Stroke.

BACKGROUND: Coronary artery disease (CAD) and ischemic stroke share the same risk factors. OBJECTIVE: The aim of the study was to explore the prevalence and predictors of concomitant CAD in acute ischemic stroke patients. METHODS: One hundred and five patients (64.3 ± 15.0 years, 61 male) presenting with acute ischemic stroke documented by neuroimaging were consecutively included. All patients were carefully evaluated to determine their cardiovascular disease risk scores. The patients who had been previously shown to have ≥50% stenosis in at least one of the major coronary arteries by coronary angiography were grouped as CAD patients. RESULTS: Of the 105 stroke patients, 27 patients had documented concomitant CAD. The stroke patients with CAD had higher cardiovascular risk scores and troponin I levels and carotid plaques were more prevalent. ROC analysis determined cut-off values as ≥22% for Framingham Heart Study Risk Score, ≥0.05 ng/mL for Troponin I, and ≥0.80 mm for carotid artery intima-media thickness to predict concomitant CAD. During 6 months of follow-up, among the 78 stroke patients without documented CAD, 16 patients had experienced major cardiovascular events including myocardial infarction, recurrent stroke, or cardiovascular death. These patients had higher Framingham Heart Study Risk Score and high-sensitive C reactive protein levels. CONCLUSION: Our study suggests stroke patients with higher Framingham Heart Study Risk Score and troponin I levels and carotid plaques be further investigated for the presence of concomitant CAD.

The evaluation of right ventricle dyssynchrony by speckle tracking echocardiography in systemic sclerosis patients.

PURPOSE: Systemic sclerosis (SSc) is associated with right ventricle (RV) remodeling and dysfunction. The primary aim of this study was to evaluate RV dyssynchrony (RV-Dys) in SSc patients using two-dimensional speckle tracking echocardiography (2D-STE). METHODS: Fifty-five SSc patients with functional class I-II and 45 healthy controls were consecutively included and underwent 2D-STE. RV-Dys was defined as the standard deviation of time to peak strain of mid and basal segments of RV free wall and interventricular septum. SSc group was further classified according to the presence of pulmonary arterial hypertension (PAH). Patients with tricuspid regurgitant velocity >2.8 m/s with additional echocardiographic PAH signs were defined as SSc PAH (+). RESULTS: SSc patients had lower RV longitudinal strain (RV-LS) (-17.6 ± 4.6% vs. -20.8 ± 2.8%, p < 0.001) and greater RV-Dys (49.9 ± 25.4 ms vs 24.3 ± 11.8 ms, p = 0.006) than controls despite no significant difference in conventional echocardiographic variables regarding RV function. Although SSc PAH(+) patients had lower RV-LS and higher RV-Dys than SSc PAH(-) patients, the differences were not statistically significant. The only independent predictor of RV-Dys was RV-LS (ß:-0.324 [-3.89- -0.45]; p = 0.014). CONCLUSION: SSc patients had not only reduced RV-LS but also impaired RV synchronicity even as conventional echocardiographic variables were preserved.

A Color-Shifting Near-Infrared Fluorescent Aptamer-Fluorophore Module for Live-Cell RNA Imaging.

Fluorescent light-up RNA aptamers (FLAPs) have become promising tools for visualizing RNAs in living cells. Specific binding of FLAPs to their non-fluorescent cognate ligands results in a dramatic fluorescence increase, thereby allowing RNA imaging. Here, we present a color-shifting aptamer-fluorophore system, where the free dye is cyan fluorescent and the aptamer-dye complex is near-infrared (NIR) fluorescent. Unlike other reported FLAPs, this system enables ratiometric RNA imaging. To design the color-shifting system, we synthesized a series of environmentally sensitive benzopyrylium-coumarin hybrid fluorophores which exist in equilibrium between a cyan fluorescent spirocyclic form and a NIR fluorescent zwitterionic form. As an RNA tag, we evolved a 38-nucleotide aptamer that selectively binds the zwitterionic forms with nanomolar affinity. We used this system as a light-up RNA marker to image mRNAs in the NIR region and demonstrated its utility in ratiometric analysis of target RNAs expressed at different levels in single cells.

Is there an increased cardiovascular risk in patients with prolactinoma? A challenging question.

PURPOSE: Epicardial adipose tissue thickness (EATT) is considered to be a surrogate for visceral fat and a novel cardiovascular risk indicator. Hyperprolactinemia has been shown to be associated with increased cardiovascular risk. The aim was to evaluate the association between EATT, carotid intima media thickness (CIMT), and cardiac functions in patients with prolactinoma. METHODS: Patients with the diagnosis of prolactinoma were included. The control group consisted of healthy age matched individuals with normal prolactin levels. Prolactin, fasting blood glucose (FBG), insulin, hemoglobin A1c (HbA1c), alanine aminotransferase (ALT), total cholesterol, triglycerides, and high (HDL) and low density lipoprotein (LDL) cholesterol were measured. EATT, CIMT, cardiac systolic, and diastolic functions were determined using echocardiography. RESULTS: We evaluated 67 patients with prolactinoma (aged 40.7 ± 11.9 years, F/M: 51/16) and 57 controls (aged 42.5 ± 7.4 years, F/M: 36/21). Of the 67 patients, 24 had normal prolactin levels. FBG level was higher in prolactinoma patients than in controls. Patients and controls had similar HbA1c, HOMA-IR, ALT, total, HDL, LDL cholesterol, and triglycerides levels, and similar cardiac systolic and diastolic functions. Prolactinoma patients had greater EATT (3.0 ± 0.5 mm vs. 2.6 ± 0.4 mm, p < 0.001) and CIMT (0.57 ± 0.08 mm vs. 0.52 ± 0.04 mm, p = 0.03) than controls. EATT was correlated with body mass index, FBG, HbA1c, and triglyceride levels. CONCLUSIONS: EATT and CIMT were greater in patients with prolactinoma, although they had normal cardiac systolic and diastolic functions.

IDO1-Targeted Therapy Does Not Control Disease Development in the Eµ-TCL1 Mouse Model of Chronic Lymphocytic Leukemia.

Indoleamine-2,3-dioxygenase 1 (IDO1), a tryptophan (Trp)-catabolizing enzyme producing metabolites such as kynurenine (Kyn), is expressed by myeloid-derived suppressor cells (MDSCs) and associated with cancer immune escape. IDO1-expressing monocytic MDSCs were shown to accumulate in patients with chronic lymphocytic leukemia (CLL) and to suppress T cell activity and induce suppressive regulatory T cells (Tregs) in vitro. In the Eµ-TCL1 mouse model of CLL, we observed a strong upregulation of IDO1 in monocytic and granulocytic MDSCs, and a significantly increased Kyn to Trp serum ratio. To explore the potential of IDO1 as a therapeutic target for CLL, we treated mice after adoptive transfer of Eµ-TCL1 leukemia cells with the IDO1 modulator 1-methyl-D-tryptophan (1-MT) which resulted in a minor reduction in leukemia development which disappeared over time. 1-MT treatment further led to a partial rescue of the immune cell changes that are induced with CLL development. Similarly, treatment of leukemic mice with the clinically investigated IDO1 inhibitor epacadostat reduced the frequency of Tregs and initially delayed CLL development slightly, an effect that was, however, lost at later time points. In sum, despite the observed upregulation of IDO1 in CLL, its inhibition is not sufficient to control leukemia development in the Eµ-TCL1 adoptive transfer model.

Aptamer-based proximity labeling guides covalent RNA modification.

We describe the development of a proximity-induced bio-orthogonal inverse electron demand Diels-Alder reaction that exploits the high-affinity interaction between a dienophile-modified RhoBAST aptamer and its tetramethyl rhodamine methyltetrazine substrate. We applied this concept for covalent RNA labeling in proof-of-principle experiments.

Super-resolution RNA imaging using a rhodamine-binding aptamer with fast exchange kinetics.

Overcoming limitations of previous fluorescent light-up RNA aptamers for super-resolution imaging, we present RhoBAST, an aptamer that binds a fluorogenic rhodamine dye with fast association and dissociation kinetics. Its intermittent fluorescence emission enables single-molecule localization microscopy with a resolution not limited by photobleaching. We use RhoBAST to image subcellular structures of RNA in live and fixed cells with about 10-nm localization precision and a high signal-to-noise ratio.