The mechanism of 14-3-3η in thyroxine induced mitophagy in cardiomyocytes.

Hyperthyroidism is becoming increasingly important as an independent risk factor for cardiovascular disease, eventually resulting in cardiac hypertrophy and heart failure. The 14-3-3 protein family subtypes regulate many cellular processes in eukaryotes by interacting with a diverse array of client proteins. Considering that the 14-3-3η protein protects cardiomyocytes by affecting mitochondrial function, exploring the biological influence and molecular mechanisms by which 14-3-3η alleviates the cardiac hypertrophy of hyperthyroidism is imperative. In vivo and in vitro, RT-PCR, Western blot, and Mitochondrial tracking assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. The in vivo and in vitro results indicated that overexpression of the 14-3-3η ameliorated thyroxine-induced cardiomyocyte hypertrophy, whereas knockdown of the 14-3-3η protein aggravated thyroxine-induced cardiomyocyte hypertrophy. Additionally, overexpression of the 14-3-3η protein reduces thyroxine-induced mitochondrial damage and mitophagy in cardiomyocytes. Overexpression of 14-3-3η protein improves excessive mitophagy in the myocardium caused by thyroxine and thus prevents cardiac hypertrophy.

Carbon-based Flame Retardants for Polymers: A Bottom-up Review.

This state-of-the-art review is geared toward elucidating the molecular understanding of the carbon-based flame-retardant mechanisms for polymers via holistic characterization combining detailed analytical assessments and computational material science. The use of carbon-based flame retardants, which include graphite, graphene, carbon nanotubes (CNTs), carbon dots (CDs), and fullerenes, in their pure and functionalized forms are initially reviewed to evaluate their flame retardancy performance and to determine their elevation of the flammability resistance on various types of polymers. The early transition metal carbides such as MXenes, regarded as next-generation carbon-based flame retardants, are discussed with respect to their superior flame retardancy and multifunctional applications. At the core of this review is the utilization of cutting-edge molecular dynamics (MD) simulations which sets a precedence of an alternative bottom-up approach to fill the knowledge gap through insights into the thermal resisting process of the carbon-based flame retardants, such as the formation of carbonaceous char and intermediate chemical reactions offered by the unique carbon bonding arrangements and microscopic in-situ architectures. Combining MD simulations with detailed experimental assessments and characterization, a more targeted development as well as a systematic material synthesis framework can be realized for the future development of advanced flame-retardant polymers.

CRISPR-Cas9 mediated dsRNase knockout improves RNAi efficiency in the fall armyworm.

Lepidopteran insects are refractory to RNA interference (RNAi) response, especially to orally delivered double-stranded RNA (dsRNA). High nuclease activity in the midgut lumen is proposed as one of the major reasons for RNAi insensitivity. We identified three dsRNase genes highly expressed in the midgut of fall armyworm (FAW), Spodoptera frugiperda. The genomic region harboring those three dsRNase genes was deleted using the CRISPR-Cas9-mediated genome editing method. A homozygous line with deletion of three dsRNase genes was produced. dsRNA degradation by midgut lumen contents of mutant larvae was lower than in wild-type larvae. Feeding dsRNA targeting the inhibitor of apoptosis (IAP) gene increased knockdown of the target gene and mortality in mutants compared to wild-type larvae. These results suggest that dsRNases in the midgut contribute to RNAi inefficiency in FAW. Formulations that protect dsRNA from dsRNase degradation may improve RNAi efficiency in FAW and other lepidopteran insects.

2D Ferromagnetic M3GeTe2 (M = Ni/Fe) for Boosting Intermediates Adsorption toward Faster Water Oxidation.

In this work, 2D ferromagnetic M3GeTe2 (MGT, M = Ni/Fe) nanosheets with rich atomic Te vacancies (2D-MGTv) are demonstrated as efficient OER electrocatalyst via a general mechanical exfoliation strategy. X-ray absorption spectra (XAS) and scanning transmission electron microscope (STEM) results validate the dominant presence of metal-O moieties and rich Te vacancies, respectively. The formed Te vacancies are active for the adsorption of OH* and O* species while the metal-O moieties promote the O* and OOH* adsorption, contributing synergistically to the faster oxygen evolution kinetics. Consequently, 2D-Ni3GeTe2v exhibits superior OER activity with only 370 mV overpotential to reach the current density of 100 mA cm-2 and turnover frequency (TOF) value of 101.6 s-1 at the overpotential of 200 mV in alkaline media. Furthermore, a 2D-Ni3GeTe2v-based anion-exchange membrane (AEM) water electrolysis cell (1 cm2) delivers a current density of 1.02 and 1.32 A cm-2 at the voltage of 3 V feeding with 0.1 and 1 m KOH solution, respectively. The demonstrated metal-O coordination with abundant atomic vacancies for ferromagnetic M3GeTe2 and the easily extended preparation strategy would enlighten the rational design and fabrication of other ferromagnetic materials for wider electrocatalytic applications.

Laser Speckle Contrast Imaging Guides Needling Treatment of Vascular Complications from Dermal Fillers.

BACKGROUND: Although laser Doppler imaging (LDI) accurately delineates a hypoperfused area to help target hyaluronidase treatment, laser speckle contrast imaging (LSCI) is more appropriate for assessing microvascular hemodynamics and has greater reproducibility than LDI. This study investigated the use of LSCI in the evaluation and treatment of six patients who developed vascular complications after facial dermal filler injections. METHODS: The areas of vascular occlusion were accurately defined in real time by LSCI and were more precise than visual inspections or photographic evidence for guiding needling and hyaluronidase treatment. RESULTS: All patients had achieved satisfactory outcomes as early as Day 2 of treatment and no procedure-related complications were reported after a median follow-up of 9.5 (7-37) days. CONCLUSION: LSCI accurately and noninvasively delineated vascular occlusions in real time among patients experiencing complications of facial dermal filler injections. Moreover, LSCI was more accurate than visual and photographic evaluations. Clinicians can use LSCI to reliably follow-up therapeutic outcomes after salvage interventions for vascular occlusions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Azadirachtin Inhibits Nuclear Receptor HR3 in the Prothoracic Gland to Block Larval Ecdysis in the Fall Armyworm, Spodoptera frugiperda.

Azadirachtin has been used to control agricultural pests for a long time; however, the molecular mechanism of azadirachtin on lepidopterans is still not clear. In this study, the fourth instar larvae of fall armyworm were fed with azadirachtin, and then the ecdysis was blocked in the fourth instar larval stage (L4). The prothoracic glands (PGs) of the treated larvae were dissected for RNA sequencing to determine the effect of azadirachtin on ecdysis inhibition. Interestingly, one of the PG-enriched genes, the nuclear hormone receptor 3 (HR3), was decreased after azadirachtin treatment, which plays a critical role in the 20-hydroxyecdysone action during ecdysis. To deepen the understanding of azadirachtin on ecdysis, the HR3 was knocked out by using the CRISPR/Cas9 system, while the HR3 mutants displayed embryonic lethal phenotype; thus, the stage-specific function of HR3 during larval molting was not enabled to unfold. Hence, the siRNA was injected into the 24 h L4 larvae to knock down HR3. After 96 h, the injected larvae were blocked in the old cuticle during ecdysis which is consistent with the azadirachtin-treated larvae. Taken together, we envisioned that the inhibition of ecdysis in the fall armyworm after the azadirachtin treatment is due to an interference with the expression of HR3 in PG, resulting in larval mortality. The results in this study specified the understanding of azadirachtin on insect ecdysis and the function of HR3 in lepidopteran in vivo.

Enzalutamide Prior to Radium-223 Is Associated with Better Overall Survival in Metastatic Castration-Resistant Prostate Cancer Patients Compared to Abiraterone-A Retrospective Study.

Metastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months, p = 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%, p = 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003-0.231, p = 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis.

Optimisation of Additives to Maximise Performance of Expandable Graphite-Based Intumescent-Flame-Retardant Polyurethane Composites.

The effect of varying the weight percentage composition (wt.%) of low-cost expandable graphite (EG), ammonium polyphosphate (APP), fibreglass (FG), and vermiculite (VMT) in polyurethane (PU) polymer was studied using a traditional intumescent flame retardant (IFR) system. The synergistic effect between EG, APP, FG, and VMT on the flame retardant properties of the PU composites was investigated using SEM, TGA, tensile strength tests, and cone calorimetry. The IFR that contained PU composites with 40 wt.% EG displayed superior flame retardant performance compared with the composites containing only 20 w.t.% or 10 w.t.% EG. The peak heat release rate, total smoke release, and carbon dioxide production from the 40 wt.% EG sample along with APP, FG, and VMT in the PU composite were 88%, 93%, and 92% less than the PU control sample, respectively. As a result, the synergistic effect was greatly influenced by the compactness of the united protective layer. The PU composite suppressed smoke emission and inhibited air penetrating the composite, thus reducing reactions with the gas volatiles of the material. SEM images and TGA results provided positive evidence for the combustion tests. Further, the mechanical properties of PU composites were also investigated. As expected, compared with control PU, the addition of flame-retardant additives decreased the tensile strength, but this was ameliorated with the addition of FG. These new PU composite materials provide a promising strategy for producing polymer composites with flame retardation and smoke suppression for construction materials.

Sniffer Dogs Diagnose Lung Cancer by Recognition of Exhaled Gases: Using Breathing Target Samples to Train Dogs Has a Higher Diagnostic Rate Than Using Lung Cancer Tissue Samples or Urine Samples.

INTRODUCTION: Sniffer dogs can diagnose lung cancer. However, the diagnostic yields of different samples and training methods for lung cancer remain undetermined. OBJECTIVE: Six dogs were trained in three stages with the aim of improving the diagnostic yield of lung cancer by comparing training methods and specimens. METHODS: The pathological tissues of 53 lung cancer patients and 6 non-lung cancer patients in the Department of Thoracic Surgery of Kaohsiung Chang Gung Hospital were collected, and the exhaled breath samples and urine samples were collected. Urine and exhaled breath samples were also collected from 20 healthy individuals. The specimens were sent to the Veterinary Department of Pingtung University of Science and Technology. RESULTS: The dogs had a very low response rate to urine target samples in the first and second stages of training. The experimental results at the second stage of training found that after lung cancer tissue training, dogs were less likely to recognize lung cancer and healthy controls than through breath target training: the response rate to exhaled breathing target samples was about 8-55%; for urine target samples, it was only about 5-30%. When using exhaled air samples for training, the diagnosis rate of these dogs in lung cancer patients was 71.3% to 97.6% (mean 83.9%), while the false positive rate of lung cancer in the healthy group was 0.5% to 27.6% (mean 7.6%). Compared with using breathing target samples for training, the diagnosis rate of dogs trained with lung cancer tissue lung cancer was significantly lower (p < 0.05). The sensitivity and specificity of lung cancer tissue training (50.4% and 50.1%) were lower than the exhaled breath target training (91.7% and 85.1%). There is no difference in lung cancer diagnostic rate by sniff dogs among lung cancer histological types, location, and staging. CONCLUSION: Training dogs using breathing target samples to train dogs then to recognize exhaled samples had a higher diagnostic rate than training using lung cancer tissue samples or urine samples. Dogs had a very low response rate to urine samples in our study. Six canines were trained on lung cancer tissues and breathing target samples of lung cancer patients, then the diagnostic rate of the recognition of exhaled breath of lung cancer and non-lung cancer patients were compared. When using exhaled air samples for training, the diagnosis rate of these dogs in lung cancer patients was 71.3% to 97.6% (mean 83.9%), while the false positive rate of lung cancer in the healthy group was 0.5% to 27.6% (mean 7.6%). There was a significant difference in the average diagnosis rate of individual dog and overall dogs between the lung cancer group and the healthy group (p < 0.05). When using lung cancer tissue samples for training, lung cancer diagnosis rate of these dogs among lung cancer patients was only 15.5% to 40.9% (mean 27.7%). Compared with using breathing target samples for training, the diagnosis rate of dogs trained with lung cancer tissue lung cancer was significantly lower (p < 0.05). The sensitivity and specificity of lung cancer tissue training (50.4% and 50.1%) were lower than the exhaled breath target training (91.7% and 85.1%). The diagnostic rate of lung cancer by sniffer dogs has nothing to do with the current stage of lung cancer, pathologic type, and the location of tumor mass. Even in stage IA lung cancer, well-trained dogs can have a diagnostic rate of 100%. Using sniffer dogs to screen early lung cancer may have good clinical and economic benefits.

CRISPR-Cas9 Genome Editing Uncovers the Mode of Action of Methoprene in the Yellow Fever Mosquito, Aedes aegypti.

Methoprene, a juvenile hormone (JH) analog, is widely used for insect control, but its mode of action is not known. To study methoprene action in the yellow fever mosquito, Aedes aegypti, the E93 (ecdysone-induced transcription factor) was knocked out using the CRISPR-Cas9 system. The E93 mutant pupae retained larval tissues similar to methoprene-treated insects. These insects completed pupal ecdysis and died as pupa. In addition, the expression of transcription factors, broad complex and Krüppel homolog 1 (Kr-h1), increased and that of programmed cell death (PCD) and autophagy genes decreased in E93 mutants. These data suggest that methoprene functions through JH receptor, methoprene-tolerant, and induces the expression of Kr-h1, which suppresses the expression of E93, resulting in a block in PCD and autophagy of larval tissues. Failure in the elimination of larval tissues and the formation of adult structures results in their death. These results answered long-standing questions on the mode of action of methoprene.

SoxC is Required for Ecdysteroid Induction of Neuropeptide Genes During Insect Eclosion.

In insects, the shedding of the old exoskeleton is accomplished through ecdysis which is typically followed by the expansion and tanning of the new cuticle. Four neuropeptides, eclosion hormone (EH), ecdysis triggering hormone (ETH), crustacean cardioactive peptide (CCAP) and bursicon (Bur) are known to control ecdysis. However, the regulation of these neuropeptide genes is still poorly understood. Here, we report that in the red flour beetle (RFB) Tribolium castaneum and the fall armyworm (FAW) Spodoptera frugiperda, knockdown or knockout of the SoxC gene caused eclosion defects. The expansion and tanning of wings were not complete. In both RFB and FAW, the knockdown or knockout of SoxC resulted in a decrease in the expression of EH gene. Electrophoretic mobility shift assays revealed that the SfSoxC protein directly binds to a motif present in the promoter of SfEH. The luciferase reporter assays in Sf9 cells confirmed these results. These data suggest that transcription factor SoxC plays a key role in ecdysteroid induction of genes coding for neuropeptides such as EH involved in the regulation of insect eclosion.

Numerical Comparison of Restored Vertebral Body Height after Incomplete Burst Fracture of the Lumbar Spine.

BACKGROUND AND OBJECTIVES: Vertebral compression fracture is a major health care problem worldwide due to its direct and indirect negative influence on health-related quality of life and increased health care costs. Although a percutaneous surgical intervention with balloon kyphoplasty or metal expansion, the SpineJack, along with bone cement augmentation has been shown to efficiently restore and fix the lost vertebral height, 21-30% vertebral body height loss has been reported in the literature. Furthermore, the effect of the augmentation approaches and the loss of body height on the biomechanical responses in physiological activities remains unclear. Hence, this study aimed to compare the mechanical behavior of the fractured lumbar spine with different restored body heights, augmentation approaches, and posterior fixation after kyphoplasty using the finite element method. Furthermore, different augmentation approaches with bone cement and bone cement along with the SpineJack were also considered in the simulation. MATERIALS AND METHODS: A numerical lumbar model with an incomplete burst fracture at L3 was used in this study. Two different degrees of restored body height, namely complete and incomplete restorations, after kyphoplasty were investigated. Furthermore, two different augmentation approaches of the fractured vertebral body with bone cement and SpineJack along with bone cement were considered. A posterior instrument (PI) was also used in this study. Physiological loadings with 400 N + 10 Nm in four directions, namely flexion, extension, lateral bending, and axial rotation, were applied to the lumbar spine with different augmentation approaches for comparison. RESULTS: The results indicated that both the bone cement and bone cement along with the SpineJack could support the fractured vertebral body to react similarly with an intact lumbar spine under identical loadings. When the fractured body height was incompletely restored, the peak stress in the L2-L3 disk above the fractured vertebral body increased by 154% (from 0.93 to 2.37 MPa) and 116% (from 0.18 to 0.39 MPa), respectively, in the annular ground substance and nucleus when compared with the intact one. The use of the PI could reduce the range of motion and facet joint force at the implanted levels but increase the facet joint force at the upper level of the PI. CONCLUSIONS: In the present study, complete restoration of the body height, as possible in kyphoplasty, is suggested for the management of lumbar vertebral fractures.

An Investigation towards Coupling Molecular Dynamics with Computational Fluid Dynamics for Modelling Polymer Pyrolysis.

Building polymers implemented into building panels and exterior façades have been determined as the major contributor to severe fire incidents, including the 2017 Grenfell Tower fire incident. To gain a deeper understanding of the pyrolysis process of these polymer composites, this work proposes a multi-scale modelling framework comprising of applying the kinetics parameters and detailed pyrolysis gas volatiles (parent combustion fuel and key precursor species) extracted from Molecular Dynamics models to a macro-scale Computational Fluid Dynamics fire model. The modelling framework was tested for pure and flame-retardant polyethylene systems. Based on the modelling results, the chemical distribution of the fully decomposed chemical compounds was realised for the selected polymers. Subsequently, the identified gas volatiles from solid to gas phases were applied as the parent fuel in the detailed chemical kinetics combustion model for enhanced predictions of toxic gas, charring, and smoke particulate predictions. The results demonstrate the potential application of the developed model in the simulation of different polymer materials without substantial prior knowledge of the thermal degradation properties from costly experiments.

Computational investigation of particle penetration and deposition pattern in a realistic respiratory tract model from different types of dry powder inhalers.

The aim of this study was to evaluate the device performance of a new design by comparing with a typical commercial DPI. Computational fluid dynamics (CFD) coupled with the discrete element method (DEM) collision has been utilized in this study to characterize and examine the flow field and particle transportation, respectively. A typical commercial DPI and an in-house designed novel DPI with distinct design features were compared to explore their dispersion capabilities and suitability for delivery to the respiratory tract. For this exploration, realistic oral to larynx and tracheobronchial airway models consisting of bio-relevant features were adopted to enhance practical feasibility. Distinct aerosol performances were observed between the two DPIs in the respiratory tract, where the in-house DPI, in comparison with the commercial DPI, has shown approximately 30% lower deposition fraction in the mouth-throat region with approximately 7% higher escape rate in the tracheobronchial region under the identical inhalation condition. This observation demonstrates that a novel in-house designed DPI provides higher device efficiency over the selected typical commercial DPI.

Peanut Shell Derived Carbon Combined with Nano Cobalt: An Effective Flame Retardant for Epoxy Resin.

Biomass-derived carbon has been recognised as a green, economic and promising flame retardant (FR) for polymer matrix. In this paper, it is considered that the two-dimensional (2D) structure of carbonised peanut shells (PS) can lead to a physical barrier effect on polymers. The carbonised sample was prepared by the three facile methods, and firstly adopted as flame retardants for epoxy resin. The results of thermal gravimetric analysis (TGA) and cone calorimeter tests indicate that the carbon combined with nano Cobalt provides the most outstanding thermal stability in the current study. With 3 wt.% addition of the FR, both peak heat release rate (pHRR) and peak smoke production rate (PSPR) decrease by 37.9% and 33.3%, correspondingly. The flame retardancy mechanisms of the FR are further explored by XPS and TG-FTIR. The effectiveness of carbonised PS can be mainly attributed to the physical barrier effect derived by PS's 2D structure and the catalysis effect from Cobalt, which contribute to form a dense char layer.

Artificial blood vessel biofuel cell for self-powered blood glucose monitoring.

Biofuel cell (BFC) is a kind of bio-cell based on biological enzymes. The enzyme as a catalyst can interconvert renewable and sustainable energy into each other more rapidly, such as the biochemical energy in glucose and ethanol into electrical energy. In this work, artificial blood vessel and fuel cell are based on polyaniline/thermoplastic polyurethane (PANI/TPU) fiber membrane with an average fiber diameter of 1300 nm, a film thickness of 167µm, and a permeability of 18.4 mm s-1. The PANI/TPU fiber membrane was prepared by electrospinning and followedin situpolymerization. The membrane has good flexibility and mechanical properties, and can be stretched up to 200%. The advantages of good hydrophilicity, biocompatibility and high porosity make it possible to efficiently load glucose oxidase and laccase. The prepared BFC can stably output a voltage of 50 mV in simulated blood, and the output electrical signal changes significantly with the change of glucose concentration, which may be used in implantable devices or blood glucose monitoring.

Flame Retardancy and Excellent Electrical Insulation Performance of RTV Silicone Rubber.

Room temperature vulcanized (RTV) silicone rubber filled with aluminum trihydrate (ATH) is substantially engaged in electrical outdoor insulation applications. The pristine silicone rubber is highly combustible. ATH filled silicone rubber offers excellent electrical insulation but lacks in providing adequate flame retardancy. This short communication reports the novel results on improved flame retardancy of pristine and ATH filled silicone rubber whilst retaining the electrical insulation properties to a great extent. Results suggest that the presence of only one percent of graphene nanoplatelets with ATH sharply reduces the heat release rate and rate of smoke release. A minor reduction in dielectric breakdown strength and volume resistivity is noticed. Furthermore, permittivity and dielectric loss at power frequency suggest that a marginal 1% concentration of nanoplatelet with ATH is an excellent approach to fabricate flame retardant silicone rubber with an acceptable electrical insulation level.

Identifying clinical risk factors correlate with suicide attempts in patients with first episode major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is the most common mental disorder associated with suicide attempts. When a patient first visits the clinic, clinicians are often expected to make concrete diagnose about acute suicidal risk. However, the timeliness of suicide attempts correlates with patients with MDD has not been tested. METHODS: We divided 1718 first-episode and untreated MDD outpatients into those who did not have suicide attempts (non-attempts), recent suicide attempters (≤14 days before assessment) and long - dated suicide attempters (> 30 days before assessment). Positive Symptom Scale of Positive and Negative Syndrome Scale (PANSS), the 17-item Hamilton Depression Scale, 14 - item Hamilton Anxiety Scale, and clinical global impression of severity scale (CGI-S) was assessed. Body mass index, some glycolipid metabolism and thyroid hormone parameters were measured. A gradient-boosted decision trees statistical model was used to generate equally weighted classification for distinguishing recent and long - dated suicide attempters from non-attempts. RESULTS: The classifier identified higher excitement, hostility, anxiety, depression symptoms and higher free thyroxine (FT4) as risk factors for recent suicide attempters with an estimated accuracy of 87% (sensitivity, 59.1%; specificity, 61.2 %). For long - dated suicide attempters' risk factors, single status, higher anxiety and hostility symptoms, higher LDLC and lower BMI, the estimated accuracy was 88% (sensitivity, 52.8%; specificity, 49.6%). CONCLUSIONS: Risk factors for suicide attempt among patients with MDD can be identified by integrating demographic, clinical, and biological variables as early as possible during the first time see a doctor.

Interrelationships Between Oxidative Stress, Cytokines, and Psychotic Symptoms and Executive Functions in Patients With Chronic Schizophrenia.

OBJECTIVE: Accumulating evidence has demonstrated that the pathophysiology of schizophrenia is involved in various abnormalities in oxidative stress markers and cytokines closely related to synaptic plasticity. However, the interactive effects among key cytokines, oxidative stress, and executive dysfunction and symptoms of schizophrenia have not been investigated yet. METHODS: A total of 189 patients with chronic schizophrenia and 60 controls were recruited in the current study. Tumor necrosis factor α (TNF-α), interleukin (IL)-8, IL-6, and IL-2 levels; catalase, glutathione peroxidase, and superoxide dismutase (SOD) activities; and malondialdehyde (MDA) levels were determined in patients and controls. Executive function was evaluated by the Wisconsin card sorting tests, the verbal fluency tests, and the Stroop word-color test. Clinical symptoms were evaluated by the Positive and Negative Syndrome Scale. RESULTS: Relative to the controls, the patients had lower activities of SOD and glutathione peroxidase and levels of TNF-α, but higher levels of MDA, IL-8, IL-6, and IL-2 (all p values < .05). A significant negative relationship between SOD activity and IL-8 levels was found only in patients (ß = -0.44, p = .008). Furthermore, we found that an interactive effect of low TNF-α level and high MDA level was associated with negative symptoms (ß = -0.02, p = .01). Moreover, the interactive effects of IL-8 and MDA or IL-8 and SOD were correlated with executive function only in patients (ß = 0.23, p = .02; ß = 0.09, p = .03). CONCLUSIONS: Our findings suggest that the interrelationships between oxidative stress markers and cytokines occur in schizophrenia patients, which may be the basis of their pathological mechanisms underlying clinical symptoms and cognitive dysfunction.

Safety of image-guided radiotherapy in definitive radiotherapy for localized prostate cancer: a population-based analysis.

OBJECTIVES: Image-guided radiotherapy (IGRT) is a recommended advanced radiation technique that is associated with fewer acute and chronic toxicities. However, one Phase III trial showed worse overall survival in the IGRT arm. The purpose of this observational study is to evaluate the impact of IGRT on overall survival. METHODS: We used the Taiwan Cancer Registry Database to enroll cT1-4N0M0 prostate cancer patients who received definitive radiotherapy between 2011 and 2015. We used inverse probability treatment weighting (IPW) to construct balanced IGRT and non-IGRT groups. We compared the overall survival of those in the IGRT and non-IGRT groups. Supplementary analyses (SA) were performed with alternative covariates in propensity score (PS) models and PS approaches. The incidence rates of prostate cancer mortality (IPCM), other cancer mortality (IOCM), and cardiovascular mortality (ICVM) were also evaluated. RESULTS: There were 360 patients in the IGRT arm and 476 patients in the non-IGRT arm. The median follow-up time was 50 months. The 5-year overall survival was 88% in the IGRT arm and 86% in the non-IGRT arm (adjusted hazard ratio [HR] of death = 0.93; 95% CI, 0.61-1.45; p = 0.77). The SA also showed no significant differences in the overall survival between those in the IGRT and non-IGRT arms. Both groups did not significantly differ in terms of IPCM, IOCM, and ICVM. CONCLUSIONS: The overall survival of localized prostate cancer patients who underwent IGRT was not inferior to those who did not. ADVANCES IN KNOWLEDGE: We demonstrated that the overall survival for prostate cancer patients with IGRT was not worse than those who did not undergo IGRT; this important outcome comparison has not been previously examined in the general population.