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Background Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (ATII), thereby contributing to lung fibrosis in IPF. Although activation of Janus kinase 2 (JAK2) has been implicated in proliferative disorders, its role in IPF is unknown. The aim of this study was to analyze JAK2 activation in IPF, and to determine whether JAK2/STAT3 inhibition is a potential therapeutic strategy for this disease. Methods and results JAK2/p-JAK2 and STAT3/pSTAT3 expression was evaluated using quantitative real time-PCR, western blotting, and immunohistochemistry. Compared to human healthy lung tissue ( n  = 10) both proteins were upregulated in the lung tissue of IPF patients ( n  = 12). Stimulating primary ATII and lung fibroblasts with transforming growth factor beta 1 or interleukin (IL)-6/IL-13 activated JAK2 and STAT3, inducing epithelial to mesenchymal and fibroblast to myofibroblast transitions. Dual p-JAK2/p-STAT3 inhibition with JSI-124 or silencing of JAK2 and STAT3 genes suppressed ATII and the fibroblast to myofibroblast transition, with greater effects than the sum of those obtained using JAK2 or STAT3 inhibitors individually. Dual rather than single inhibition was also more effective for inhibiting fibroblast migration, preventing increases in fibroblast senescence and Bcl-2 expression, and ameliorating impaired autophagy. In rats administered JSI-124, a dual inhibitor of p-JAK2/p-STAT3, at a dose of 1 mg/kg/day, bleomycin-induced lung fibrosis was reduced and collagen deposition in the lung was inhibited, as were JAK2 and STAT3 activation and several markers of fibrosis, autophagy, senescence, and anti-apoptosis. Conclusions JAK2 and STAT3 are activated in IPF, and their dual inhibition may be an attractive strategy for treating this disease.

Mobile medical imaging devices are invaluable for clinical diagnostic purposes both in and outside healthcare institutions. Among the various imaging modalities, only a few are readily portable. Magnetic resonance imaging (MRI), the gold standard for numerous healthcare conditions, does not traditionally belong to this group. Recently, low-field MRI technology companies have demonstrated the first decisive steps towards portability within medical facilities and vehicles. However, these scanners’ weight and dimensions are incompatible with more demanding use cases such as in remote and developing regions, sports facilities and events, medical and military camps, or home healthcare. Here we present in vivo images taken with a light, small footprint, low-field extremity MRI scanner outside the controlled environment provided by medical facilities. To demonstrate the true portability of the system and benchmark its performance in various relevant scenarios, we have acquired images of a volunteer’s knee in: (i) an MRI physics laboratory; (ii) an office room; (iii) outside a campus building, connected to a nearby power outlet; (iv) in open air, powered from a small fuel-based generator; and (v) at the volunteer’s home. All images have been acquired within clinically viable times, and signal-to-noise ratios and tissue contrast suffice for 2D and 3D reconstructions with diagnostic value. Furthermore, the volunteer carries a fixation metallic implant screwed to the femur, which leads to strong artifacts in standard clinical systems but appears sharp in our low-field acquisitions. Altogether, this work opens a path towards highly accessible MRI under circumstances previously unrealistic.

Objective. To develop methods to design the complete magnetic system for a truly portable MRI scanner for neurological and musculoskeletal (MSK) applications, optimized for field homogeneity, field of view (FoV) and gradient performance compared to existing low-weight configurations. Approach. We explore optimal elliptic-bore Halbach configurations based on discrete arrays of permanent magnets. In this way, we seek to improve the field homogeneity and remove constraints to the extent of the gradient coils typical of Halbach magnets. Specifically, we have optimized a tightly-packed distribution of magnetic Nd\\(_2\\)Fe\\(_14\\)B cubes with differential evolution algorithms, and a second array of shimming magnets with interior point and differential evolution methods. We have also designed and constructed an elliptical set of gradient coils that extend over the whole magnet length, maximizing the distance between the lobe centers. These are optimized with a target field method minimizing a cost function that considers also heat dissipation. Main result. We have employed the new toolbox to build the main magnet and gradient modules for a portable MRI scanner designed for point-of-care and residential use. The elliptical Halbach bore has semi-axes of 10 & 14 cm and the magnet generates a field of 87 mT homogeneous down to 5,700 ppm (parts per million) in a 20 cm diameter FoV, it weighs 216 kg and has a width of 65 cm and a height of 72 cm. Gradient efficiencies go up to around 0.8 mT/m/A, for a maximum of 12 mT/m with in 0.5 ms with 15 A & 15 V amplifier. The distance between lobes is 28 cm, significantly increased with respect to other Halbach-based scanners. Heat dissipation is around 25 W at maximum power, and gradient deviations from linearity are below 20% in a 20 cm sphere.