The effect of the clinical phenotype of
complex (MAC) lung disease on treatment outcome and redevelopment of nontuberculous mycobacterial (NTM) lung disease after treatment completion has not been ...studied systematically.We evaluated 481 treatment-naïve patients with MAC lung disease who underwent antibiotic treatment for ≥12 months between January 2002 and December 2013.Out of 481 patients, 278 (58%) had noncavitary nodular bronchiectatic (NB) disease, 80 (17%) had cavitary NB disease and 123 (25%) had fibrocavitary disease. Favourable outcome was higher in patients with noncavitary disease (88%) than in patients with cavitary disease (76% for fibrocavitary and 78% for cavitary NB disease; p<0.05). Cavitary disease was independently associated with unfavourable outcomes (p<0.05). Out of 402 patients with favourable outcomes, 118 (29%) experienced redevelopment of NTM lung disease, with the same MAC species recurring in 65 (55%) patients. The NB form was an independent risk factor for redevelopment of NTM lung disease (p<0.05). In patients with recurrent MAC lung disease due to the same species, bacterial genotyping revealed that 74% of cases were attributable to reinfection and 26% to relapse.Treatment outcomes and redevelopment of NTM lung disease after treatment completion differed by clinical phenotype of MAC lung disease.
Red blood cells (RBCs) undergo irreversible biochemical and morphological changes during storage, contributing to the hemorheological changes of stored RBCs, which causes deterioration of ...microvascular perfusion in vivo. In this study, a home-built optofluidic system for laser speckle imaging of flowing stored RBCs through a transparent microfluidic channel was employed. The speckle decorrelation time (SDT) provides a quantitative measure of RBC changes, including aggregation in the microchannel. The SDT and relative light transmission intensity of the stored RBCs were monitored for 42 days. In addition, correlations between the decorrelation time, RBC flow speed through the channel, and relative light transmission intensity were obtained. The SDT of stored RBCs increased as the storage duration increased. The SDTs of the RBCs stored for 21 days did not significantly change. However, for the RBCs stored for over 35 days, the SDT increased significantly from 1.26 ± 0.27 ms to 6.12 ± 1.98 ms. In addition, we measured the relative light transmission intensity and RBC flow speed. As the RBC storage time increased, the relative light transmission intensity increased, whereas the RBC flow speed decreased in the microchannel. The optofluidic laser speckle image decorrelation time provides a quantitative measure of assessing the RBC condition during storage. Laser speckle image decorrelation analysis may serve as a convenient assay to monitor the property changes of stored RBCs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this letter, a self-refreshing multi-level memory-in-pixel (MIP) circuit for liquid crystal display (LCD) comprising low temperature poly-silicon and oxide (LTPO) thin film transistors (TFTs) is ...proposed. Since the proposed MIP circuit features self-refreshing without embedding frame memory, power consumption can be minimized when displaying a still image. Measurement results verify that the proposed circuit successfully enables a 3-bit grayscale. The LCD employing the proposed MIP circuit consumes only 1.22 % of power compared with a conventional LCD when displaying a still image. Thus, the proposed multi-level MIP circuit is expected to enable a low-power LCD featuring higher color depth with a simple structure.
Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-ΔG genotype, which encodes functional IFN-λ4 ...protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness. HCV infection induced IFN-λ4 expression at mRNA and protein levels in primary human hepatocytes (PHHs). In hepatoma cells, IFNL4 gene transfection or recombinant IFN-λ4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent manner and potently blocked IFN-α signalling. The ISG15/USP18-mediated IFN-α unresponsiveness was demonstrated by transfection of siRNAs targeting ISG15 and/or USP18. This potent IFN-λ4 effect was related to prolonged ISG expression after IFNL4 gene transfection. DAA treatment of HCV-infected PHHs reduced the expression of IFN-λs, including IFN-λ4, and restored IFN-α responsiveness. These results demonstrate that virus-induced IFN-λ4 potently blocks IFN-α signalling by inducing high protein levels of ISG15 and USP18. Moreover, the data clearly demonstrate that DAA therapy restores IFN-α responsiveness in HCV-infected cells.
Platelet aggregation and adhesion are critically involved in both normal hemostasis and thrombosis during vascular injury. Before any surgery, it is important to identify the number of platelets and ...their functionality to reduce the risk of bleeding; therefore, platelet function testing is a requirement. We introduce a novel evaluation method of assessing platelet function with laser speckle contrast imaging. The speckle decorrelation time (SDT) of the blood flowing through a microfluidic channel chip provides a quantitative measure of platelet aggregation. We compared SDTs of whole blood and platelet-poor blood, i.e., whole blood stripped of its buffy coat region, and found a marked reduction in decorrelation time for platelet-poor blood. The measured SDT of platelet-poor blood was 1.04 ± 0.21 ms, while that of whole blood was 2.64 ± 0.83 ms. To further characterize the sensitivity of our speckle decorrelation time-based platelet function testing (SDT-PFT), we added various agonists involved in platelet aggregation, including adenosine diphosphate (ADP), epinephrine (EPI), and arachidonic acid (AA). In this study, the results show that whole blood with ADP resulted in the largest SDT, followed by whole blood with AA, whole blood with EPI, whole blood without agonist, and platelet-poor blood with or without agonist. These findings show that SDT-PFT has the potential for rapid screening of bleeding disorders and monitoring of anti-platelet therapies with only a small volume of blood.
Among the various thermal stress indices, apparent temperature (AT) is closely related to public health indicators, and consequently is widely used by weather agencies around the world. Therefore, in ...this paper we estimate the changes in AT and contributing components in Korea as a whole and in five major cities (Seoul, Gwanju, Daegu, Daejeon, and Busan) using national standard climate scenarios based on the coupled model inter-comparison project (CMIP6). In the present day, high AT occurs in major cities due to high temperature (TAS) and relative humidity (RH). Our findings reveal that even when TAS is relatively low, large AT occurs with higher humidity. Notably, in future warmer climate conditions, high AT may first appear in the five major cities and then extend to the surrounding areas. An increase in TAS and RH during the pre-hot season (March to June) may lead to earlier occurrence of thermal risks in future warmer climate conditions and more frequent occurrence of high thermal stress events. Our study can serve as a reference for future information on thermal risk changes in Korea. Considering those who have not adapted to high temperature environments, our findings imply that thermal risks will become more serious and that heat adaptation strategies will be needed during the pre-hot season under future warmer climate conditions.
Background and Aim: This study investigated the administration of combination therapy, allogeneic natural killer (NK) cells and pembrolizumab in the treatment of advanced biliary tract cancer to ...determine the safety and tolerability (phase 1) and the efficacy and safety (phase 2a). Methods: Forty patients (phase 1, n = 6; phase 2a, n = 34) were enrolled between December 2019 and June 2021. The patients received highly activated allogeneic NK cells (“SMT-NK”) on weeks 1 and 2 and pembrolizumab on week 1. This 3-week schedule (one cycle) was repeated until confirmed disease progression, intolerable adverse events (AEs), patient withdrawal, or finishing the maximum treatment schedule. The tumor response was evaluated after every three cycles. Results: In phase 1, four patients (66.7%) experienced seven AEs, but no severe AE was observed. In phase 2a, 126 AEs occurred in 29 patients (85.3%). Severe AEs (≥grade 3) were reported in 16 patients (47.1%). The overall response rate (ORR) was 17.4% in the full analysis set and 50.0% in the per-protocol set. Conclusions: SMT-NKs plus pembrolizumab resulted in no severe AEs directly related to the drug combination. The combination therapy also exerted antitumor activity with improved efficacy compared to the recent monotherapy with pembrolizumab in patients with advanced biliary tract cancer.
For the clinical application of semi-quantitative anti-SARS-CoV-2 antibody tests, the analytical performance and titer correlation of the plaque reduction neutralization test (PRNT) need to be ...investigated. We evaluated the analytical performance and PRNT titer-correlation of one surrogate virus neutralization test (sVNT) kit and three chemiluminescent assays. We measured the total antibodies for the receptor-binding domain (RBD) of the spike protein, total antibodies for the nucleocapsid protein (NP), and IgG antibodies for the RBD. All three chemiluminescent assays showed high analytical performance for the detection of SARS-CoV-2 infection, with a sensitivity ≥ 98% and specificity ≥ 99%; those of the sVNT were slightly lower. The representativeness of the neutralizing activity of PRNT ND
≥ 20 was comparable among the four immunoassays (Cohen's kappa ≈ 0.80). Quantitative titer correlation for high PRNT titers of ND
≥ 50, 200, and 1,000 was investigated with new cut-off values; the anti-RBD IgG antibody kit showed the best performance. It also showed the best linear correlation with PRNT titer in both the acute and convalescent phases (Pearson's R 0.81 and 0.72, respectively). Due to the slowly waning titer of anti-NP antibodies, the correlation with PRNT titer at the convalescent phase was poor. In conclusion, semi-quantitative immunoassay kits targeting the RBD showed neutralizing activity that was correlated by titer; measurement of anti-NP antibodies would be useful for determining past infections.
The incidences of various esophageal diseases (e.g., congenital esophageal stenosis, tracheoesophageal fistula, esophageal atresia, esophageal cancer) are increasing, but esophageal tissue is ...difficult to be recovered because of its weak regenerative capability. There are no commercialized off-the-shelf alternatives to current esophageal reconstruction and regeneration methods. Surgeons usually use ectopic conduit tissues including stomach and intestine, presumably inducing donor site morbidity and severe complications. To date, polymer-based esophageal substitutes have been studied as an alternative. However, the fabrication techniques are nearly limited to creating only cylindrical outer shapes with the help of additional apparatus (e.g., mandrels for electrospinning) and are unable to recapitulate multi-layered characteristic or complex-shaped inner architectures. 3D bioprinting is known as a suitable method to fabricate complex free-form tubular structures with desired pore characteristic. In this study, we developed a extrusion-based 3D printing technique to control the size and the shape of the pore in a single extrusion process, so that the fabricated structure has a higher flexibility than that fabricated in the conventional process. Based on this suggested technique, we developed a bioprinted 3D esophageal structure with multi-layered features and converged with biochemical microenvironmental cues of esophageal tissue by using decellularizedbioinks from mucosal and muscular layers of native esophageal tissues. The two types of esophageal tissue derived-decellularized extracellular matrix bioinks can mimic the inherent components and composition of original tissues with layer specificity. This structure can be applied to full-thickness circumferential esophageal defects and esophageal regeneration.
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