Non-specialist ultrasound measuring of access flow: new technology

A new ultrasound instrument has been developed, using vector Doppler and embedded machine intelligence, to enable measurement of access flow rates by non-specialists. Ultrasound measurement of access flow can be performed with the patient off the dialysis machine, avoiding the hemodynamic changes that may affect indicator-dilution methods. A research version of the instrument was tested on flow phantoms simulating graft flow, and showed accuracy better than 5%. A non-specialist measured flow in the access grafts of 7 consenting dialysis patients; the instrument showed flows commensurate with indicator-dilution-measured flows, but with less variability. Measurements were made in less than 5 min per patient. The cost per measurement is calculated to be significantly less than that of present methods of measuring flow. The new instrument may become a useful tool for monitoring flow in accesses to extend their life.     

Impact of age-associated increase in 2′-O-methylation of miRNAs on aging and neurodegeneration in Drosophila

MicroRNAs (miRNAs) are 20- to ∼24-nucleotide (nt) small RNAs that impact a variety of biological processes, from development to age-associated events. To study the role of miRNAs in aging, studies have profiled the levels of miRNAs with time. However, evidence suggests that miRNAs show heterogeneity in length and sequence in different biological contexts. Here, by examining the expression pattern of miRNAs by Northern blot analysis, we found that Drosophila miRNAs show distinct isoform pattern changes with age. Surprisingly, an increase of some miRNAs reflects increased 2′-O-methylation of select isoforms. Small RNA deep sequencing revealed a global increase of miRNAs loaded into Ago2, but not into Ago1, with age. Our data suggest increased loading of miRNAs into Ago2, but not Ago1, with age, indicating a mechanism for differential loading of miRNAs with age between Ago1 and Ago2. Mutations in Hen1 and Ago2, which lack 2′-O-methylation of miRNAs, result in accelerated neurodegeneration and shorter life span, suggesting a potential impact of the age-associated increase of 2′-O-methylation of small RNAs on age-associated processes. Our study highlights that miRNA 2′-O-methylation at the 3′ end is modulated by differential partitioning of miRNAs between Ago1 and Ago2 with age and that this process, along with other functions of Ago2, might impact age-associated events in Drosophila.     

Chitosan-g-oligo/polylactide copolymer non-woven fibrous mats containing protein: from solid-state synthesis to electrospinning

Graft-copolymers based on bioresorbable synthetic (oligo-/polylactide) and natural (chitosan and collagen/gelatin) components were synthesized through solid-state reactive co-extrusion and used for fabrication of fibrous non-woven mats via the electrospinning technique. The effect of the macromolecular features of the initial components on the copolymer characteristics was evaluated using FTIR-spectroscopy, differential scanning calorimetry and elemental analysis. Dynamic light scattering analysis showed that the copolymers have a tendency to form stable ultra-fine dispersions with a mean size of macromolecular aggregates of 150 nm within chlorinated solvents. The copolymer-containing non-woven fibrous mats were fabricated via an electrospinning procedure using chloroform as a solvent. An effect of the copolymer composition on the casting solution''s viscosity, conductivity and surface tension was evaluated. Scanning electron microscopy showed that the obtained mats consist of randomly distributed fibers with a mean size of ∼5 μm and a more complex morphology than mats fabricated from neat polylactide. The proposed mechanochemical approach to obtain hybrid copolymeric compositions differs from typical liquid-phase methods in terms of high efficiency, simplicity and cleanness.

Amphiphilic chitosan-g-oligo/polylactide graft-copolymers were synthesized through solid-state reactive co-extrusion and used for fabrication of fibrous non-woven mats via the electrospinning technique using chloroform as a solvent.     

Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

Background

Gender can influence post-infarction cardiac remodeling.

Objective

To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI).

Methods

Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium.

Results

MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI.

Conclusions

Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.     

Embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma,and medulloepithelioma share molecular similarity and comprise a single clinicopathological entity

Three histological variants are known within the family of embryonal rosette-forming neuroepithelial brain tumors. These include embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma (EBL), and medulloepithelioma (MEPL). In this study, we performed a comprehensive clinical, pathological, and molecular analysis of 97 cases of these rare brain neoplasms, including genome-wide DNA methylation and copy number profiling of 41 tumors. We identified uniform molecular signatures in all tumors irrespective of histological patterns, indicating that ETANTR, EBL, and MEPL comprise a single biological entity. As such, future WHO classification schemes should consider lumping these variants into a single diagnostic category, such as embryonal tumor with multilayered rosettes (ETMR). We recommend combined LIN28A immunohistochemistry and FISH analysis of the 19q13.42 locus for molecular diagnosis of this tumor category. Recognition of this distinct pediatric brain tumor entity based on the fact that the three histological variants are molecularly and clinically uniform will help to distinguish ETMR from other embryonal CNS tumors and to better understand the biology of these highly aggressive and therapy-resistant pediatric CNS malignancies, possibly leading to alternate treatment strategies.