This work presents a new additive manufacturing electrochemical device with conductive graphene and polylactic acid (PLA) filament and its application for epinephrine sensing. A three-electrode ...configuration based on a screen-printed electrode architecture and an easy-to-connect connector was designed. The sensor surface was chemically treated with dimethylformamide (DMF) to remove the insulating thermoplastic and expose the graphene binding groups. The scanning electron microscopy (SEM) results showed that the surface PLA was removed and the graphene nanofibers exposed, which corroborated the X-ray diffraction spectra (XRD). As a proof of concept, the G-PLA electrode was applied for the determination of epinephrine in human blood samples by square wave voltammetry with a linear range from 4.0 to 100 µmol L−1 and a limit of detection of 0.2 µmol L−1. Based on the results obtained and sensor application, 3D-printed G-PLA proved an excellent choice for epinephrine sensing purposes.
Nearly 8% of the human population carries an inactivating point mutation in the gene that encodes the cardioprotective enzyme aldehyde dehydrogenase 2 (ALDH2). This genetic polymorphism (ALDH2*2) is ...linked to more severe outcomes from ischemic heart damage and an increased risk of coronary artery disease (CAD), but the underlying molecular bases are unknown. We investigated the ALDH2*2 mechanisms in a human model system of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) generated from individuals carrying the most common heterozygous form of the ALDH2*2 genotype. We showed that the ALDH2*2 mutation gave rise to elevated amounts of reactive oxygen species and toxic aldehydes, thereby inducing cell cycle arrest and activation of apoptotic signaling pathways, especially during ischemic injury. We established that ALDH2 controls cell survival decisions by modulating oxidative stress levels and that this regulatory circuitry was dysfunctional in the loss-of-function ALDH2*2 genotype, causing up-regulation of apoptosis in cardiomyocytes after ischemic insult. These results reveal a new function for the metabolic enzyme ALDH2 in modulation of cell survival decisions. Insight into the molecular mechanisms that mediate ALDH2*2-related increased ischemic damage is important for the development of specific diagnostic methods and improved risk management of CAD and may lead to patient-specific cardiac therapies.
Chronic neutrophilic leukemia (CNL), atypical chronic myeloid leukemia (aCML), and myelodysplastic/myeloproliferative neoplasms, unclassifiable (MDS/MPN-U) are a group of rare and heterogeneous ...myeloid disorders. There is strong morphologic resemblance among these distinct diagnostic entities as well as a lack of specific molecular markers and limited understanding of disease pathogenesis, which has made diagnosis challenging in certain cases. The treatment has remained empirical, resulting in dismal outcomes. We, therefore, performed whole-exome and RNA sequencing of these rare hematologic malignancies and present the most complete survey of the genomic landscape of these diseases to date. We observed a diversity of combinatorial mutational patterns that generally do not cluster within any one diagnosis. Gene expression analysis reveals enrichment, but not cosegregation, of clinical and genetic disease features with transcriptional clusters. In conclusion, these groups of diseases represent a continuum of related diseases rather than discrete diagnostic entities.
•First comprehensive genomic and transcriptomic profiling of CNL, aCML, and MDS/MPN-U.•Diagnoses represent a continuum of related diseases rather than discrete diagnostic entities.
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Purpose
To compare the diagnostic performance of multi-detector CT arthrography (CTA) and 1.5-T MR arthrography (MRA) in detecting hyaline cartilage lesions of the shoulder, with arthroscopic ...correlation.
Patients and methods
CTA and MRA prospectively obtained in 56 consecutive patients following the same arthrographic procedure were independently evaluated for glenohumeral cartilage lesions (modified Outerbridge grade ≥2 and grade 4) by two musculoskeletal radiologists. The cartilage surface was divided in 18 anatomical areas. Arthroscopy was taken as the reference standard. Diagnostic performance of CTA and MRA was compared using ROC analysis. Interobserver and intraobserver agreement was determined by
κ
statistics.
Results
Sensitivity and specificity of CTA varied from 46.4 to 82.4 % and from 89.0 to 95.9 % respectively; sensitivity and specificity of MRA varied from 31.9 to 66.2 % and from 91.1 to 97.5 % respectively. Diagnostic performance of CTA was statistically significantly better than MRA for both readers (all
p
≤ 0.04). Interobserver agreement for the evaluation of cartilage lesions was substantial with CTA (
κ
= 0.63) and moderate with MRA (
κ
= 0.54). Intraobserver agreement was almost perfect with both CTA (
κ
= 0.94–0.95) and MRA (
κ
= 0.83–0.87).
Conclusion
The diagnostic performance of CTA and MRA for the detection of glenohumeral cartilage lesions is moderate, although statistically significantly better with CTA.
Key points
•
CTA has moderate diagnostic performance for detecting glenohumeral cartilage substance loss.
•
MRA has moderate diagnostic performance for detecting glenohumeral cartilage substance loss.
•
CTA is more accurate than MRA for detecting cartilage substance loss.
A recent European report on men’s health shows that it lags behind that of women. Alan White and colleagues analyse the problems and call for more policy, practice, and research aimed specifically at ...men
The effect of nitrogen on the dynamic strain again behavior of a Fe–18% Mn–0.6% C twinning-induced plasticity steel was investigated by means of in situ infrared thermography during tensile testing. ...The addition of nitrogen affected the initiation of the Portevin–Le Châtelier bands and the characteristic shape of the serrations on the stress–strain curve. Also, nitrogen additions resulted in an increase in the critical strain for dynamic strain aging.
The plasminogen (Plg)/plasmin (Pla) system is associated with a variety of biological activities beyond the classical dissolution of fibrin clots, including cell migration, tissue repair, and ...inflammation. Although the capacity of Plg/Pla to induce cell migration is well defined, the mechanism underlying this process in vivo is elusive. In this study, we show that Pla induces in vitro migration of murine fibroblasts and macrophages (RAW 264.7) dependent on the MEK/ERK pathway and by requiring its proteolytic activity and lysine binding sites. Plasmin injection into the pleural cavity of BALB/c mice induced a time-dependent influx of mononuclear cells that was associated with augmented ERK1/2 and IκB-α phosphorylation and increased levels of CCL2 and IL-6 in pleural exudates. The inhibition of protease activity by using a serine protease inhibitor leupeptin or two structurally different protease-activated receptor-1 antagonists (SCH79797 and RWJ56110) abolished Pla-induced mononuclear recruitment and ERK1/2 and IκB-α phosphorylation. Interestingly, inhibition of the MEK/ERK pathway abolished Pla-induced CCL2 upregulation and mononuclear cell influx. In agreement with a requirement for the CCL2/CCR2 axis to Pla-induced cell migration, the use of a CCR2 antagonist (RS504393) prevented the Plg/Pla-induced recruitment of mononuclear cells to the pleural cavity and migration of macrophages at transwell plates. Therefore, Pla-induced mononuclear cell recruitment in vivo was dependent on protease-activated receptor-1 activation of the MEK/ERK/NF-κB pathway, which led to the release of CCL2 and activation of CCR2.
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