► Resveratrol may play important roles in enhancing chemotherapeutic potential. ► Combination of clofarabine and resveratrol produces a synergistic anti-proliferative effect. ► Combination treatment ...produces little toxicity in normal mesothelial cells. ► Our data underline the significance of Akt and Sp1 as novel targets.
Dietary phytochemicals as adjuvants have been suggested to play important roles in enhancing chemotherapeutic potential owing to multitargeted chemopreventive properties and lack of substantial toxicity. Here, we investigated the efficacy of the combined treatment of various phytochemicals with the anticancer drug clofarabine in malignant mesothelioma MSTO-211H cells and normal mesothelial MeT-5A cells. The combined treatment of resveratrol and clofarabine produced a synergistic antiproliferative effect in MSTO-211H cells, but not in MeT-5A cells. In MSTO-211H cells, the nuclear accumulation of Sp1 and the levels of p-Akt, Sp1, c-Met, cyclin D1, and p21 were effectively decreased by the combined treatment of them. In combination with clofarabine, the ability of resveratrol to reduce the contents of Sp1 and its target gene products was also evident in a time- and dose-dependent experiment. The inhibition of phosphoinositide 3-kinase using Ly294002 augmented a decrease in the p21 level induced by their combination, but it showed no significant effects on expression of Sp1 and cyclin D1. Taken together, the data provide evidence that the synergistic antiproliferative effect of resveratrol and clofarabine is linked to the inhibition of Akt and Sp1 activities, and suggest that this combination may have therapeutic value in treatment of malignant mesothelioma.
Tissue engineering has played a very significant role in the medical field with an ever-growing demand for various tissue donations. One crucial factor is the fabrication of a desirable artificial ...three-dimensional (3D) tissue scaffold to act as the extracellular matrix (ECM), meeting the complex requirements for specific cell cultures. Existing scaffold fabrication techniques and systems used in constructing extracellular matrix are two-dimensionally limiting, expensive, and time-consuming. For instance, some simple fabrication methods cannot control fabricated structures with morphologies accurately, while others may introduce harmful organic solvents into scaffolds during the fabrication processes. To achieve an optimal scaffold for tissue engineering, we developed a novel 3D printing system capable of printing tissue scaffold structures with improved efficiency. The uniqueness of our system is the transparent diffractive optical elements (DOEs) of linear binary Fresnel lens fabricated to control the luminous intensity distribution. These DOEs of different patterns are arranged in series on a coverslip with each optical element designed to diffact and focus incident light at a particular plane within the device. Coupled with other optical components of the system, 3D woodpile scaffolds were printed in an effective and efficient one-step light exposure process to photo cross-link the polymer solution upon demand. The combination of photo cross-linking and diffractive optical technique incorporated within our system enables the patterning of polymer solutions within seconds, making large-scale fast production not only feasible, but also making printing of complex features simple. With this system, 3D two-layered woodpile structures were successfully fabricated within 3 seconds. While cell toxicity studies showed that the scaffold can be used for tissue engineering.
: This study compared the levels of knowledge of physical illnesses and patterns of health behaviors between patients with psychosis and the general population.
: A total of 712 participants were ...included in the study; 292 patients with a schizophrenia spectrum disorder and 420 healthy controls matched for age and gender. Questionnaires were administered to study participants to determine the level of knowledge of chronic physical illnesses such as cancer, hypertension, and diabetes mellitus and health-related behavior. Results from the two study groups were compared to identify differences in knowledge of physical illness and health-related behaviors.
: Compared with healthy controls, patients with psychosis were less likely to undergo regular medical check-ups and engage in exercise. Patients with psychosis had poorer knowledge of physical illnesses, and were more likely to smoke, be overweight, or have diabetes. Patients with psychosis were significantly less likely to acknowledge the importance of early detection of cancer and controlling hypertension and diabetes, independent of education and type of medical insurance. Patients who smoked were significantly less likely to agree with the statement on the relationship between smoking and physical illnesses. Patients not undergoing regular medical check-ups were significantly less likely to agree with statements concerning the need for cancer screening.
: Patients with psychosis demonstrated lower levels of knowledge of physical illnesses and a lack of understanding of preventive behaviors. Low levels of knowledge were associated with poor health-related behaviors. Education of physical health should be provided to patients with psychosis.
Polymer-nanoparticle composites find relevance in various fields ranging from optoelectronics to the biomedical sciences. Various efforts have been made to devise fabrication strategies that are ...simple, robust,and reproducible. Herein, we demonstrate a universal strategy to fabricate plasmon-active polymer-nanoparticle composites, exemplified by the incorporation of gold nanoparticles (AuNPs) into a triethylene glycol dimethacrylate (TEGDMA) polymer scaffold. The TEGDMA scaffold was synthesized on a planar glass support substrate via surface-initiated atomic transfer radical polymerization, followed by the immersion of the TEGDMA-coated glass substrate in a solution of AuNPs prepared via conventional wet-chemical synthesis. This led to the strong attachment of AuNPs to the TEGDMA nanolobes, which was confirmed by the UV absorption peak at 527 nm, due to localized surface plasmon resonance of AuNPs. More importantly, the nanolobe architecture facilitates nanoparticle trapping while allowing molecular access to the nanoparticle surface. This enabled us to further functionalize the incorporated AuNPs with thrombin binding aptamer and utilize the biofunctionalized polymer-nanoparticle composite as a thrombin sensor. The synergistic combination of metallic nanoparticles acting as a sensing module with a nonfouling polymer matrix acting both as a nonrigid scaffold and to screen biomolecules allowed the detection of thrombin with good sensitivity down to 0.01 ng/mL with a linear range over three orders of magnitude. Our work paves the way for the fabrication of reliable biomolecular sensors based on the polymer brush-nanoparticle architecture.Graphic Abstract
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•Silver rich LTCC an e-waste has been recycled and valorized.•Selectively, Ag was leached and recovered as nanopowder.•The process can circulate the Ag within the industry in a close ...loop.•Brings back the material to production stream and address the circular economy.•Can be part of cradle-to-cradle technology and lower the futuristic carbon economy.
Considering the value of silver metal and silver nanoparticles, the waste generated during manufacturing of low temperature co-fired ceramic (LTCC) were recycled through the simple yet cost effective process by chemical-metallurgy. Followed by leaching optimization, silver was selectively recovered through precipitation. The precipitated silver chloride was valorized though silver nanoparticle synthesis by a simple one-pot greener synthesis route. Through leaching-precipitation optimization, quantitative selective recovery of silver chloride was achieved, followed by homogeneous pure silver nanoparticle about 100nm size were synthesized. The reported recycling process is a simple process, versatile, easy to implement, requires minimum facilities and no specialty chemicals, through which semiconductor manufacturing industry can treat the waste generated during manufacturing of LTCC and reutilize the valorized silver nanoparticles in manufacturing in a close loop process. Our reported process can address issues like; (i) waste disposal, as well as value-added silver recovery, (ii) brings back the material to production stream and address the circular economy, and (iii) can be part of lower the futuristic carbon economy and cradle-to-cradle technology management, simultaneously.
Background
This study evaluated whether an addition of bevacizumab to erlotinib improves clinical outcomes in patients with advanced EGFR‐mutated non–small cell lung cancer (NSCLC).
Methods
This is ...an open‐label, multicenter, randomized Phase 2 study in South Korea. Chemonaïve patients with Stage IIIB/IV NSCLC with EGFR 19 deletion or L858R mutation were eligible. Asymptomatic brain metastasis (BM) was enrolled without local treatment. Patients received either erlotinib plus bevacizumab or erlotinib.
Results
Between December 2016 and March 2019, 127 patients were randomly assigned to receive erlotinib plus bevacizumab (n = 64) or erlotinib (n = 63). Fifty‐nine (46.5%) patients had baseline BM. Fewer patients in the erlotinib plus bevacizumab arm received radiotherapy for BM than in the erlotinib arm (10.3% vs. 40.0%). A trend toward longer progression‐free survival (PFS) was observed in the erlotinib plus bevacizumab arm compared with the erlotinib alone arm; however, it was not statistically significant (median PFS, 17.5 months vs. 12.4 months; hazard ratio HR, 0.74; 95% CI, 0.51–1.08; p = .119). The unplanned subgroup analysis showed a longer PFS with erlotinib plus bevacizumab in patients with BM (median PFS, 18.6 months vs. 10.3 months; HR, 0.54; 95% CI, 0.31–0.95; p = .032). Grade 3 or worse adverse events occurred in 56.6% of the erlotinib plus bevacizumab arm and 20.6% of the erlotinib arm.
Conclusions
Although it was not statistically significant, a trend to improvement in PFS was observed in patients with erlotinib plus bevacizumab compared to erlotinib alone.
Plain Language Summary
A randomized Phase 2 study compared erlotinib with or without bevacizumab in previously untreated patients with advanced non–small cell lung cancer with EGFR mutation. The erlotinib plus bevacizumab failed to improve median progression‐free survival compared with the erlotinib alone. However, the progression‐free survival benefit from erlotinib plus bevacizumab was found in patients with brain metastasis with no severe hemorrhagic adverse effects.
A trend to improvement in progression‐free survival was observed in patients with advanced EGFR‐mutated non–small cell lung cancer treated with erlotinib plus bevacizumab compared with erlotinib alone. The progression‐free survival benefit from erlotinib plus bevacizumab was most significant in patients with brain metastasis with no severe hemorrhagic adverse effects.
To investigate associations between stress, resilience, and burnout in three emotional job sectors.
We conducted a multi-group comparative study using structural equation modeling and latent mean ...analysis. In total, 806 participants (403 call center consultants, 270 mental health workers, and 133 school counselors) completed self-administered questionnaires including the Perceived Stress Scale, Korean version of the Connor-Davidson Resilience Scale, and Maslach Burnout InventoryGeneral Survey.
Stress had significant direct effects on resilience and burnout, and resilience had significant direct effects on burnout in all groups. Resilience partially mediated these relationships among call center consultants and school counselors. Stress and burnout were highest in call center consultants, followed, in order, by mental health workers and school counselors. Resilience was highest in school counselors, followed, in order, by mental health workers and call center consultants. The effect size of the latent mean difference was highest for burnout, followed, in order, by resilience and stress. Psychiatry Investig.
Our findings suggest that stress caused by emotional labor can contribute to burnout. Interventions targeted at different sectors are needed to reduce burnout.
This study aimed to apply various ranges of citric acid levels in the mouth and T-cannula to compare the validity with instrumental aspiration measures in patients with tracheostomy. Sixty-one ...patients underwent the citric acid cough reflex test (CRT) and videofluoroscopic swallowing study (VFSS). Citric acid was delivered via facemask and T-cannula at concentrations of 0.4 mol/L, 0.6 mol/L, and 0.8 mol/L. Further, we recorded the coughing count and presence of ≥ 2 (C2) and ≥ 5 (C5) coughs. CRT via facemask at 0.4 mol/L C2, 0.6 mol/L C5, and 0.8 mol/L C2 and C5 were significantly associated with the presence of tracheal aspiration during VFSS. The sensitivity and specificity were optimized at 0.8 mol/L C2 for mouth inhalation and at 0.8 mol/L C5 for T-cannula inhalation. There was a significant difference in the coughing count during CRT at 0.4 mol/L and 0.8 mol/L via mouth inhalation between patients with or without tracheal aspiration, but not via T-cannula. The AUC for 0.8 mol/L facemask inhalation was 0.701. The optimal cut-off value of coughing count was thrice with 84.62% sensitivity and 50.00% specificity on the ROC curve. Afferent sensory nerve desensitization around and below the tracheostomy site could affect coughing reflex initiation and decrease the sensitivity of detecting aspiration in tracheotomized patients. The citric acid CRT via facemask can reliably detect tracheal aspiration and presence of coughing reflex compared to that via T-cannula in patients with tracheostomy.
This study aimed to explore the prognostic impact of spatial distribution of tumor‐infiltrating lymphocytes (TILs) quantified by deep learning (DL) approaches based on digitalized whole‐slide images ...stained with hematoxylin and eosin in patients with colorectal cancer (CRC). The prognostic impact of spatial distributions of TILs in patients with CRC was explored in the Yonsei cohort (n = 180) and validated in The Cancer Genome Atlas (TCGA) cohort (n = 268). Two experienced pathologists manually measured TILs at the most invasive margin (IM) as 0–3 by the Klintrup–Mäkinen (KM) grading method and this was compared to DL approaches. Inter‐rater agreement for TILs was measured using Cohen's kappa coefficient. On multivariate analysis of spatial TIL features derived by DL approaches and clinicopathological variables including tumor stage, microsatellite instability, and KRAS mutation, TIL densities within 200 μm of the IM (f_im200) remained the most significant prognostic factor for progression‐free survival (PFS) (hazard ratio HR 0.004 95% confidence interval, CI, 0.0001–0.15, p = 0.0028) in the Yonsei cohort. On multivariate analysis using the TCGA dataset, f_im200 retained prognostic significance for PFS (HR 0.031 95% CI 0.001–0.645, p = 0.024). Inter‐rater agreement of manual KM grading was insignificant in the Yonsei (κ = 0.109) and the TCGA (κ = 0.121) cohorts. The survival analysis based on KM grading showed statistically significant different PFS in the TCGA cohort, but not the Yonsei cohort. Automatic quantification of TILs at the IM based on DL approaches shows prognostic utility to predict PFS, and could provide robust and reproducible TIL density measurement in patients with CRC.
Serosurveillance studies reveal the actual disease burden and herd immunity level in the population. In Seoul, Korea, a cross-sectional investigation showed 0.07% anti-severe acute respiratory ...syndrome coronavirus-2 antibody seropositivity among 1,500 outpatients of the university hospitals. Low seroprevalence reflects well-implemented social distancing. Serosurveillance should be repeated as the pandemic progresses.
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