Endothelial function,regulation of angiogenesis and embryonic central hemodynamics in ART-conceived pregnancies

Abstract

This study was undertaken to compare the concentrations of pro- and anti-angiogenic growth factors, nitric oxide (NO) stable metabolites in maternal serum and embryonic left ventricular (LV) isovolumic relaxation time (IRT, ms) during the first trimester in two groups of women: with pregnancy conceived by assisted reproductive technologies (ART, n?=?39) and normally conceived (control group, n?=?68) pregnancy. The concentration of vasoconstrictor endothelin 1 was 45.5 times more in ART than in control group. On the contrary, the concentrations of NO stable metabolites in ART were 1.9 times less than in control women. The assessment of angiogenic suppressors in ART women demonstrates the decrease in s-endoglin concentration was 1.6 times and in soluble receptor to vascular endothelial growth factor concentration was 2.0 times in comparison with control group. There was a significant increase in LV IRT in ART embryos in comparison to control ones. These data suggest significant changes in pro- anti-angiogenic factors balance and increase in vascular impedance in ART-conceived embryos.     

Glioma-Induced Disruption of Resting-State Functional Connectivity and Amplitude of Low-Frequency Fluctuations in the Salience Network

BACKGROUND AND PURPOSE:Cognitive challenges are prevalent in survivors of glioma, but their neurobiology is incompletely understood. The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on resting-state functional connectivity and amplitude of low-frequency fluctuations of the salience network, a key neural network associated with cognition.MATERIALS AND METHODS:Sixty-nine patients with glioma (mean age, 48.74 [SD, 14.32] years) who underwent resting-state fMRI were compared with 31 healthy controls (mean age, 49.68 [SD, 15.54] years). We identified 4 salience network ROIs: left/right dorsal anterior cingulate cortex and left/right anterior insula. Average salience network resting-state functional connectivity and amplitude of low-frequency fluctuations within the 4 salience network ROIs were computed.RESULTS:Patients with gliomas showed decreased overall salience network resting-state functional connectivity (P = .001) and increased amplitude of low-frequency fluctuations in all salience network ROIs (P < .01) except in the left dorsal anterior cingulate cortex. Compared with controls, patients with left-sided gliomas showed increased amplitude of low-frequency fluctuations in the right dorsal anterior cingulate cortex (P = .002) and right anterior insula (P < .001), and patients with right-sided gliomas showed increased amplitude of low-frequency fluctuations in the left anterior insula (P = .002). Anterior tumors were associated with decreased salience network resting-state functional connectivity (P < .001) and increased amplitude of low-frequency fluctuations in the right anterior insula, left anterior insula, and right dorsal anterior cingulate cortex. Patients with high-grade gliomas had decreased salience network resting-state functional connectivity compared with healthy controls (P < .05). The right anterior insula showed increased amplitude of low-frequency fluctuations in patients with grade II and IV gliomas compared with controls (P < .01).CONCLUSIONS:By demonstrating decreased resting-state functional connectivity and an increased amplitude of low-frequency fluctuations related to the salience network in patients with glioma, this study adds to our understanding of the neurobiology underpinning observable cognitive deficits in these patients. In addition to more conventional functional connectivity, amplitude of low-frequency fluctuations is a promising functional-imaging biomarker of tumor-induced vascular and neural pathology.

Detrimental effects of cancer on cognitive function and, consequently, on the quality of life are emerging as a key focus of cancer survivorship both in research and clinical practice.^1,2 Brain tumors have been shown to affect memory, processing, and attention in patients; however, their underlying neurobiology is incompletely understood.³ Using resting-state functional MR imaging (rsfMRI) to evaluate changes in cognitive resting-state networks may provide a better understanding of the pathology underlying the observable cognitive disruptions in gliomas, the most common primary brain tumor in adults.A “triple network model” of neurocognitive pathology has been proposed, which encompasses the default mode network, involved in mind wandering; the central executive network, involved in decision-making; and the salience network (SN), implicated in modulating activation of the default mode network and central executive network by detecting the presence of salient stimuli.^4-8 While previous rsfMRI research has largely focused on tumor-induced changes in the default mode network,^9,10 our study examined the less-studied SN, a network rooted in the anterior insula and the dorsal anterior cingulate cortex.⁶Prior studies evaluating gliomas and SN resting-state functional connectivity (RSFC) provided conflicting results in small patient samples: Maesawa et al¹⁰ found no significant differences in the SN in 12 patients, while Liu et al¹¹ more recently found decreased SN connectivity in 13 patients. Gliomas impact the integrity of the neurovascular unit to varying degrees, resulting in neurovascular uncoupling that has been reported to confound fMRI interpretations in patients with brain tumors.^12-14 Additionally, research has reported neuronal plasticity manifested by structural reorganization and functional remodeling of neural networks in patients with gliomas with possible alterations in clinically observable cognitive manifestations.^15-17 An rsfMRI metric, the amplitude of low-frequency fluctuations (ALFF), has recently shown promise as a biomarker for brain plasticity and hemodynamic characterization, including neurovascular uncoupling in patients with gliomas.^15-19The purpose of this study was to investigate the effect of glioma presence and tumor characteristics on overall RSFC and regional normalized ALFF within the SN in a large patient population. We hypothesized that there would be decreased average SN RSFC and altered ALFF in patients with gliomas compared with healthy controls. Recent studies have acknowledged that gliomas have variable effects on network integrity based on lesion location and proximity to network ROIs,^20-22 and unilateral gliomas can be associated with plasticity in both the ipsilateral and contralateral hemispheres.^11,17 Research also supports differences in resting-state network reorganization in aggressive high-grade gliomas compared with slower-growing low-grade gliomas.^20,23 Therefore, we also hypothesized that there would be differences in average SN RSFC and regional ALFF in patients based on the anterior-versus-posterior location, hemispheric side, and grade of glioma.     

Premature Ticagrelor Discontinuation in Secondary Prevention of Atherosclerotic CVD: JACC Review Topic of the Week

Ticagrelor is a cornerstone of modern antithrombotic therapy alongside aspirin in patients with acute coronary syndrome and after percutaneous coronary intervention. Adverse effects such as bleeding and dyspnea have been associated with premature ticagrelor discontinuation, which may limit any potential advantage of ticagrelor over clopidogrel. The randomized trials of ticagrelor captured adverse events, offering the opportunity to more precisely quantify these effects across studies. Therefore, a meta-analysis of 4 randomized clinical trials of ticagrelor conducted between January 2007 and June 2017 was performed to quantify the incidence and causes of premature ticagrelor discontinuation. Among 66,870 patients followed for a median 18 months, premature ticagrelor discontinuation was seen in 25%; bleeding was the most common cause of discontinuation followed by dyspnea. Versus the comparators, the relative risk of dyspnea-related discontinuation during follow-up was 6.4-fold higher, the relative risk of bleeding was 3.2-fold higher, and the relative risk of discontinuation due to any adverse event was 59% higher for patients receiving ticagrelor. Understanding these potential barriers to adherence to ticagrelor is crucial for informed patient-physician decision making and can inform future efforts to improve ticagrelor adherence. This review discusses the incidence, causes, and biological mechanisms of ticagrelor-related adverse effects and offers strategies to improve adherence to ticagrelor.     

Ultrasound-Assist Extrusion Methods for the Fabrication of Polymer Nanocomposites Based on Polypropylene/Multi-Wall Carbon Nanotubes

Isotactic polypropylenes (iPP) with different melt flow indexes (MFI) were used to fabricate nanocomposites (NCs) with 10 wt % loadings of multi-wall carbon nanotubes (MWCNTs) using ultrasound-assisted extrusion methods to determine their effect on the morphology, melt flow, and electrical properties of the NCs. Three different types of iPPs were used with MFIs of 2.5, 34 and 1200 g/10 min. Four different NC fabrication methods based on melt extrusion were used. In the first method melt extrusion fabrication without ultrasound assistance was used. In the second and third methods, an ultrasound probe attached to a hot chamber located at the exit of the die was used to subject the sample to fixed frequency and variable frequency, respectively. The fourth method is similar to the first method, with the difference being that the carbon nanotubes were treated in a fluidized air-bed with an ultrasound probe before being used in the fabrication of the NCs with no ultrasound assistance during extrusion. The samples were characterized by MFI, Optical microscopy (OM), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), electrical surface resistivity, and electric charge. MFI decreases in all cases with addition of MWCNTs with the largest decrease observed for samples with the highest MFI. The surface resistivity, which ranged from 10¹³ to 10⁵ Ω/sq, and electric charge, were observed to depend on the ultrasound-assisted fabrication method as well as on the melt flow index of the iPP. A relationship between agglomerate size and area ratio with electric charge was found. Several trends in the overall data were identified and are discussed in terms of MFI and the different fabrication methods.     

Synthesis,Antimicrobial Activity,and Behavioral Response Effects of N-Substituted 4-Aryl-2-Hydroxy-4-Oxobut-2-Enoic Acid Hydrazides and Their Metal Complexes

Pharmaceutical Chemistry Journal - N-Substituted 4-aryl-2-hydroxy-4-oxobut-2-enoic acid hydrazides and their complexes with Ni(II), Mn(II), Co(II), Cu(II), and Zn(II) were prepared. Their...     

Interpersonal Counseling in the Treatment of Adolescent Depression: A Randomized Controlled Effectiveness and Feasibility Study in School Health and Welfare Services

In order to offer early and accessible treatment for adolescents with depression, brief and effective treatments in adolescents’ everyday surroundings are needed. This randomized controlled trial studied the preliminary effectiveness, feasibility, and acceptability of interpersonal counseling (IPC) and brief psychosocial support (BPS) in school health and welfare services. The study was conducted in the 28 lower secondary schools of a large city in Southern Finland, randomized to provide either IPC or BPS. Help-seeking 12–16-year-old adolescents with mild-to-moderate depression, with and without comorbid anxiety, were included in the study. Fifty-five adolescents received either 6 weekly sessions of IPC or BPS and two follow-up sessions. Outcome measures included self- and clinician-rated measures of depression, global functioning, and psychological distress/well-being. To assess feasibility and acceptability of the treatments, adolescents’ and counselors’ treatment compliance and satisfaction with treatment were assessed. Both treatments were effective in reducing depressive disorders and improving adolescents’ overall functioning and well-being. At post-treatment, in both groups, over 50% of adolescents achieved recovery based on self-report and over 70% based on observer report. Effect sizes for change were medium or large in both groups at post-treatment and increased at 6-month follow-up. A trend indicating greater baseline symptom severity among adolescents treated in the IPC-providing schools was observed. Adolescents and counselors in both groups were satisfied with the treatment, and 89% of the adolescents completed the treatments and follow-ups. This trial suggests that both IPC and BPS are feasible, acceptable, and effective treatments for mild-to-moderate depression in the school setting. In addition, IPC seems effective even if comorbid anxiety exists. Our study shows that brief, structured interventions, such as IPC and BPS, are beneficial in treating mild-to-moderate depression in school settings and can be administered by professionals working at school.

Trial registrationhttp://www.clinicaltrials.gov. Unique identifier: NCT03001245.