White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis

ObjectiveDespite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations.MethodsTwenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls.ResultsFocal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T₂ signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities.ConclusionWhite matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T₂ signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T₂ signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.     

Engineering of NIR fluorescent PEGylated poly(RGD) proteinoid polymers and nanoparticles for drug delivery applications in chicken embryo and mouse models

Proteinoids are non-toxic biodegradable polymers based on thermal step-growth polymerization of natural or synthetic amino acids. Hollow proteinoid nanoparticles (NPs) may then be formed via a self-assembly process of the proteinoid polymers in an aqueous solution. In the present article polymers and NPs based on d-arginine, glycine and l-aspartic acid, poly(R^DGD), were synthesized for tumor targeting, particularly due to the high affinity of the RGD motif to areas of angiogenesis. Near IR fluorescent P(R^DGD) NPs were prepared by encapsulating the fluorescent NIR dye indocyanine green (ICG) within the formed P(R^DGD) NPs. Here, we investigate the effect of the covalent conjugation of polyethylene glycol (PEG), with different molecular weights, to the surface of the near IR encapsulated P(R^DGD) NPs on the release of the dye to human serum due to bio-degradation of the proteinoid NPs and on the uptake by tumors. This work illustrates that the release of the encapsulated ICG from the non-PEGylated NPs is significantly faster than for that observed for the PEGylated NPs, and that the higher molecular weight is the bound PEG spacer the slower is the dye release profile. In addition, in a chicken embryo model, the non-PEGylated ICG-encapsulated P(R^DGD) NPs exhibited a higher uptake in the tumor region in comparison to the PEGylated ICG-encapsulated P(R^DGD) NPs. However, in a tumor xenograft mouse model, which enables a prolonged experiment, the importance of the PEG is clearly noticeable, when a high concentration of PEGylated P(R^DGD) NPs was accumulated in the area of the tumor compared to the non-PEGylated P(R^DGD). Moreover, the length of the PEG chain plays a major role in the ability to target the tumor. Hence, we can conclude that selectivity towards the tumor area of non-PEGylated and the PEGylated ICG-encapsulated P(R^DGD) NPs can be utilized for targeting to areas of angiogenesis, such as in the cases of tumors, wounds or cuts, etc.

Synthesis of NIR/ICG PEGylated poly(R^DGD) proteinoid NPs and their drug delivery towards mCherry-labeled 4T1 tumor.     

Augmentation index predicts mortality in patients with aortic stenosis: an echo-tracking study

The International Journal of Cardiovascular Imaging - Aortic valve stenosis (AS) shares similarities with the atherosclerotic process but little is known about the effect of the mechanical...     

Reliability and accuracy assessment of morphometric measurements obtained with software for three-dimensional reconstruction of brain aneurysms relative to cerebral angiography measures

ObjectiveTo analyze the reliability and accuracy of morphological measurements of software employed to three-dimensionally reconstruct aneurysms and vessels (VMTKlab, version 1.6.1,) with computed tomography angiography (CTA) as the source of images. Agreement with measurements from three-dimensional digital subtraction angiography (3 D-DSA) was evaluated.MethodsWe evaluated 40 patients presenting with aneurysmal subarachnoid hemorrhage (aSAH). We analyzed four main variables of the aneurysm morphology: absolute height (size), neck (maximum neck width), perpendicular height, and maximum width. The CTA images were uploaded to the software and then segmented to reconstruct the aneurysm. This new method was compared to the current gold standard—3D reconstruction of pretreatment cerebral angiography. We used intraclass correlation coefficient (ICC) and Bland-Altman plot analyses to evaluate the agreement between these methods.ResultsThe ICCs obtained for absolute height, neck, perpendicular height, and maximum width were 0.85, 0.57, 0.85, and 0.89, respectively. This implied good agreement except for the neck of the aneurysm (moderate agreement). Bland-Altman plots are presented for the four indexes. The average of the differences was not significant in terms of absolute height, perpendicular height, and maximum width indicating good agreement. However, it was significant for the neck of the aneurysm.ConclusionsWe report good agreement between the values generated using VMTKlab and cerebral angiography for three of the four main variables. Discrepancies in neck diameter are not surprising and its underestimation with a traditional delineation from cerebral angiography has been reported before.     

Bibliometric indexes,databases and impact factors in cardiology

Bibliometry is a quantitative statistical technique to measure levels of production and dissemination of knowledge, as well as a useful tool to track the development of an scientific area. The valuation of production required for recognition of researchers and magazines is accomplished through tools called bibliometricindexes, divided into quality indicators and scientific impact. Initially developed for monographs of statistical measures especially in libraries, today bibliometrics is mainly used to evaluate productivity of authors and citation repercussion. However, these tools have limitations and sometimes provoke controversies about indiscriminate application, leading to the development of newer indexes. It is important to know the most common search indexes and use it properly even acknowledging its limitations as it has a direct impact in their daily practice, reputation and funds achievement.