Color gamut characteristics of diffractive-light guides of near-eye augmented reality glasses.

We delve into the distinctive color gamut characteristics resulting from color dispersion of surface relief grating (SRG) and wavelength degeneracy of volume holographic optical element (VHOE) in a diffractive light guide. While a laser-like spectrum achieves an impressive 194% sRGB color gamut for both cases, it proves unsuitable for VHOE light guides due to limitations in breaking the field of view (FOV) of the display. Conversely, a broad-band light source, such as LEDs, offers continuous FOV but reduces the common color gamut to 50% sRGB. We then present a newly designed VHOE light guide capable of achieving the common color gamut of 130% sRGB using two multiplexed holograms of each color, closely matching the 133% sRGB achieved by an SRG light guide. This article presents the first theoretical methodology to elucidate color performance of diffractive light guides utilizing VHOEs with holographic multiplexing, affirming their suitability for crafting high-quality near-eye display.

Pioneering Data Processing for Convolutional Neural Networks to Enhance the Diagnostic Accuracy of Traditional Chinese Medicine Pulse Diagnosis for Diabetes.

Traditional Chinese medicine (TCM) has relied on pulse diagnosis as a cornerstone of healthcare assessment for thousands of years. Despite its long history and widespread use, TCM pulse diagnosis has faced challenges in terms of diagnostic accuracy and consistency due to its dependence on subjective interpretation and theoretical analysis. This study introduces an approach to enhance the accuracy of TCM pulse diagnosis for diabetes by leveraging the power of deep learning algorithms, specifically LeNet and ResNet models, for pulse waveform analysis. LeNet and ResNet models were applied to analyze TCM pulse waveforms using a diverse dataset comprising both healthy individuals and patients with diabetes. The integration of these advanced algorithms with modern TCM pulse measurement instruments shows great promise in reducing practitioner-dependent variability and improving the reliability of diagnoses. This research bridges the gap between ancient wisdom and cutting-edge technology in healthcare. LeNet-F, incorporating special feature extraction of a pulse based on TMC, showed improved training and test accuracies (73% and 67%, respectively, compared with LeNet's 70% and 65%). Moreover, ResNet models consistently outperformed LeNet, with ResNet18-F achieving the highest accuracy (82%) in training and 74% in testing. The advanced preprocessing techniques and additional features contribute significantly to ResNet18-F's superior performance, indicating the importance of feature engineering strategies. Furthermore, the study identifies potential avenues for future research, including optimizing preprocessing techniques to handle pulse waveform variations and noise levels, integrating additional time-frequency domain features, developing domain-specific feature selection algorithms, and expanding the scope to other diseases. These advancements aim to refine traditional Chinese medicine pulse diagnosis, enhancing its accuracy and reliability while integrating it into modern technology for more effective healthcare approaches.

Ramelteon protects against social defeat stress-associated abnormal behaviors.

Psychological stress affects the neuroendocrine regulation, which modulates mental status and behaviors. Melatonin, a hormone synthesized primarily by the pineal gland, regulates many brain functions, including circadian rhythms, pain, sleep, and mood. Selective pharmacological melatonin agonist ramelteon has been clinically used to treat mood and sleep disorders. Posttraumatic stress disorder (PTSD) is a psychiatric condition associated with severe trauma; it is generally triggered by traumatic events, which lead to severe anxiety and uncontrollable trauma recall. We recently reported that repeated social defeat stress (RSDS) may induce robust anxiety-like behaviors and social avoidance in mice. In the present study, we investigated whether melatonin receptor activation by melatonin and ramelteon regulates RSDS-induced behavioral changes. Melatonin treatment improved social avoidance and anxiety-like behaviors in RSDS mice. Moreover, treatment of the non-selective MT1/MT2 receptor agonist, ramelteon, markedly ameliorated RSDS-induced social avoidance and anxiety-like behaviors. Moreover, activating melatonin receptors also balanced the expression of monoamine oxidases, glucocorticoid receptors, and endogenous antioxidants in the hippocampus. Taken together, our findings indicate that the activation of both melatonin and ramelteon regulates RSDS-induced anxiety-like behaviors and PTSD symptoms. The current study also showed that the regulatory effects of neuroendocrine mechanisms and cognitive behaviors on melatonin receptor activation in repeated social defeat stress.

Dopamine agonists in restless leg syndrome treatment and their effects on sleep parameters: A systematic review and meta-analysis.

BACKGROUND: Dopamine agonists (DAs) constitute the standard therapeutic scheme for restless leg syndrome (RLS) because they have been proven to be effective. However, DAs may change sleep parameters, thus having adverse effects on patient condition. This meta-analysis clarified the effects of DAs used in RLS treatment on the sleep architecture. METHODS: PubMed, Embase, and Cochrane Central databases were searched for randomized control trials (RCT) (up to October 2023) that discussed the effects of DAs on sleep architecture in patients with RLS. A meta-analysis employing a random-effects model was conducted. The patients were divided into subgroups according to individual DAs and treatment duration (1 day or ≥4 weeks). RESULTS: Thirteen eligible randomized placebo-controlled trials were included in the assessment. The effects of three DAs (i.e., pramipexole, ropinirole, and rotigotine) on rapid eye movement (REM) sleep, slow-wave sleep (SWS), and sleep efficiency (SE) were analyzed. Overall, pramipexole significantly improved SE but decreased the percentage of REM sleep among treated patients. Ropinirole also enhanced SE compared with the placebo group. Rotigotine did not affect SE and REM sleep. Subgroup analysis found that pramipexole used for 1 day and ≥4 weeks significantly diminished the percentage of REM sleep. Ropinirole used for 1 day showed similar REM sleep patterns. Finally, none of the three DAs affected SWS. CONCLUSIONS: This meta-analysis demonstrated that DAs significantly affect sleep parameters.

Real-world efficacy, roll-out and uptake of intramuscular tixagevimab/cilgavimab as COVID-19 pre-exposure prophylaxis in people with multiple sclerosis and neuroimmunological conditions during the COVID-19 pandemic.

Background: In Australia, tixagevimab/cilgavimab 150 mg/150 mg was a government-funded pre-exposure prophylaxis for COVID-19 people with multiple sclerosis (pwMS) and other neuroimmunological conditions (pwNIc) treated with anti-CD20 antibodies or sphingosine-1-phosphate receptor modulators were eligible. Objective: To analyse the roll-out, uptake and real-world efficacy of tixagevimab/cilgavimab in the prevention and severity of COVID-19. To assess compliance with uptake depending on the location of delivery. Methods: We undertook a single-centre study. 440 pwMS and pwNIc were eligible. Logistic regression was used to assess predictors of COVID-19 during follow-up and to assess predictors of uptake among those who consented. Results: Of the eligible pwMS and pwNIc in our service, 52.7% (233/440) requested a consultation and were included in this study. Consultation resulted in 71.7% of people (167/233) receiving the treatment. Of these, 94.0% (157/167) had received three or more COVID-19 vaccines. Among those who received a single dose of tixagevimab/cilgavimab, 19.16% (32/167) tested positive for COVID-19 during the observational window. The majority of these were on ocrelizumab (68.8% (22/32)). None of those with COVID-19 required hospitalisation or supplemental oxygen. There was no difference in odds of COVID-19 during the observation period between those who received and did not receive tixagevimab/cilgavimab (adjusted OR, aOR 2.16 (95% CI 0.82 to 6.85), p=0.43). Uptake of tixagevimab/cilgavimab was highest when offered at the hospital infusion centre (aOR 3.09 (95% CI 1.08 to 9.94) relative to referral to the local pharmacy, p=0.04). Conclusion: Tixagevimab/cilgavimab administration did not protect against subsequent COVID-19 in our cohort. Compliance with uptake was influenced by administration location.

Vismodegib Potentiates Marine Antimicrobial Peptide Tilapia Piscidin 4-Induced Cytotoxicity in Human Non-Small Cell Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is a common cancer with several accepted treatments, such as chemotherapy, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, and immune checkpoint inhibitors. Nevertheless, NSCLC cells often become insensitive to these treatments, and therapeutic resistance is a major reason NSCLC still has a high mortality rate. The induction of therapeutic resistance in NSCLC often involves hedgehog, and suppression of hedgehog can increase NSCLC cell sensitivity to several conventional therapies. In our previous work, we demonstrated that the marine antimicrobial peptide tilapia piscidin 4 (TP4) exhibits potent anti-NSCLC activity in both EGFR-WT and EGFR-mutant NSCLC cells. Here, we sought to further explore whether hedgehog might influence the sensitivity of NSCLC cells to TP4. Our results showed that hedgehog was activated by TP4 in both WT and EGFR-mutant NSCLC cells and that pharmacological inhibition of hedgehog by vismodegib, a Food and Drug Administration-approved hedgehog inhibitor, potentiated TP4-induced cytotoxicity. Mechanistically, vismodegib acted by enhancing TP4-mediated increases in mitochondrial membrane potential and intracellular reactive oxygen species (ROS). MitoTempo, a specific mitochondrial ROS scavenger, abolished vismodegib/TP4 cytotoxicity. The combination of vismodegib with TP4 also reduced the levels of the antioxidant proteins catalase and superoxide dismutase, and it diminished the levels of chemoresistance-related proteins, Bcl-2 and p21. Thus, we conclude that hedgehog regulates the cytotoxic sensitivity of NSCLC cells to TP4 by protecting against mitochondrial dysfunction and suppressing oxidative stress. These findings suggest that combined treatment of vismodegib and TP4 may be a promising therapeutic strategy for NSCLC.

Evaluating the Margins of Breast Cancer Tumors by Using Digital Breast Tomosynthesis with Deep Learning: A Preliminary Assessment.

BACKGROUND: The assessment information of tumor margins is extremely important for the success of the breast cancer surgery and whether the patient undergoes a second operation. However, conducting surgical margin assessments is a time-consuming task that requires pathology-related skills and equipment, and often cannot be provided in a timely manner. To address this challenge, digital breast tomosynthesis technology was utilized to generate detailed cross-sectional images of the breast tissue and integrate deep learning algorithms for image segmentation, achieving an assessment of tumor margins during surgery. METHODS: this study utilized post-operative tissue samples from 46 patients who underwent breast-conserving treatment, and generated image sets using digital breast tomosynthesis for the training and evaluation of deep learning models. RESULTS: Deep learning algorithms effectively identifying the tumor area. They achieved a Mean Intersection over Union (MIoU) of 0.91, global accuracy of 99%, weighted IoU of 44%, precision of 98%, recall of 83%, F1 score of 89%, and dice coefficient of 93% on the training dataset; for the testing dataset, MIoU was at 83%, global accuracy at 97%, weighted IoU at 38%, precision at 87%, recall rate at 69%, F1 score at 76%, dice coefficient at 86%. CONCLUSIONS: The initial evaluation suggests that the deep learning-based image segmentation method is highly accurate in measuring breast tumor margins. This helps provide information related to tumor margins during surgery, and by using different datasets, this research method can also be applied to the surgical margin assessment of various types of tumors.

Protective effects of paeonol against cognitive impairment in lung diseases.

Pulmonary inflammation may lead to neuroinflammation resulting in neurological dysfunction, and it is associated with a variety of acute and chronic lung diseases. Paeonol is a herbal phenolic compound with anti-inflammatory and anti-oxidative properties. The aim of this study is to understand the beneficial effects of paeonol on cognitive impairment, pulmonary inflammation and its underlying mechanisms. Pulmonary inflammation-associated cognitive deficit was observed in TNFα-stimulated mice, and paeonol mitigated the cognitive impairment by reducing the expressions of interleukin (IL)-1ß, IL-6, and NOD-like receptor family pyrin domain-containing 3 (NLRP3) in hippocampus. Moreover, elevated plasma miR-34c-5p in lung-inflamed mice was also reduced by paeonol. Pulmonary inflammation induced by intratracheal instillation of TNFα in mice resulted in immune cells infiltration in bronchoalveolar lavage fluid, pulmonary edema, and acute fibrosis, and these inflammatory responses were alleviated by paeonol orally. In MH-S alveolar macrophages, tumor necrosis factor (TNF) α- and phorbol myristate acetate (PMA)-induced inflammasome activation was ameliorated by paeonol. In addition, the expressions of antioxidants were elevated by paeonol, and reactive oxygen species production was reduced. In this study, paeonol demonstrates protective effects against cognitive deficits and pulmonary inflammation by exerting anti-inflammatory and anti-oxidative properties, suggesting a powerful benefit as a potential therapeutic agent.

The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial.

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D3 supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D3 supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D3 supplementation on immune gene expression.

Comparing ocrelizumab to interferon/glatiramer acetate in people with multiple sclerosis over age 60.

BACKGROUND: Ongoing controversy exists regarding optimal management of disease modifying therapy (DMT) in older people with multiple sclerosis (pwMS). There is concern that the lower relapse rate, combined with a higher risk of DMT-related infections and side effects, may alter the risk-benefit balance in older pwMS. Given the lack of pwMS above age 60 in randomised controlled trials, the comparative efficacy of high-efficacy DMTs such as ocrelizumab has not been shown in older pwMS. We aimed to evaluate the comparative effectiveness of ocrelizumab, a high-efficacy DMT, versus interferon/glatiramer acetate (IFN/GA) in pwMS over the age of 60. METHODS: Using data from MSBase registry, this multicentre cohort study included pwMS above 60 who switched to or started on ocrelizumab or IFN/GA. We analysed relapse and disability outcomes after balancing covariates using an inverse probability treatment weighting (IPTW) method. Propensity scores were obtained based on age, country, disease duration, sex, baseline Expanded Disability Status Scale, prior relapses (all-time, 12 months and 24 months) and prior DMT exposure (overall number and high-efficacy DMTs). After weighting, all covariates were balanced. Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP) and confirmed disability improvement (CDI). RESULTS: A total of 248 participants received ocrelizumab, while 427 received IFN/GA. The IPTW-weighted ARR for ocrelizumab was 0.01 and 0.08 for IFN/GA. The IPTW-weighted ARR ratio was 0.15 (95% CI 0.06 to 0.33, p<0.001) for ocrelizumab compared with IFN/GA. On IPTW-weighted Cox regression models, HR for time to first relapse was 0.13 (95% CI 0.05 to 0.26, p<0.001). The hazard of first relapse was significantly reduced in ocrelizumab users after 5 months compared with IFN/GA users. However, the two groups did not differ in CDP or CDI over 3.57 years. CONCLUSION: In older pwMS, ocrelizumab effectively reduced relapses compared with IFN/GA. Overall relapse activity was low. This study adds valuable real-world data for informed DMT decision making with older pwMS. Our study also confirms that there is a treatment benefit in older people with MS, given the existence of a clear differential treatment effect between ocrelizumab and IFN/GA in the over 60 age group.

Extracellular vesicles purified from serum-converted human platelet lysates offer strong protection after cardiac ischaemia/reperfusion injury.

Extracellular vesicles (EVs) from cultured cells or bodily fluids have been demonstrated to show therapeutic value following myocardial infarction. However, challenges in donor variation, EV generation and isolation methods, and material availability have hindered their therapeutic use. Here, we show that human clinical-grade platelet concentrates from a blood establishment can be used to rapidly generate high concentrations of high purity EVs from sero-converted platelet lysate (SCPL-EVs) with minimal processing, using size-exclusion chromatography. Processing removed serum carrier proteins, coagulation factors and complement proteins from the original platelet lysate and the resultant SCPL-EVs carried a range of trophic factors and multiple recognised cardioprotective miRNAs. As such, SCPL-EVs protected rodent and human cardiomyocytes from hypoxia/re-oxygenation injury and stimulated angiogenesis of human cardiac microvessel endothelial cells. In a mouse model of myocardial infarction with reperfusion, SCPL-EV delivery using echo-guided intracavitary percutaneous injection produced large improvements in cardiac function, reduced scar formation and promoted angiogenesis. Since platelet-based biomaterials are already widely used clinically, we believe that this therapy could be rapidly suitable for a human clinical trial.

Inhibition of tumor migration and invasion by fenofibrate via suppressing epithelial-mesenchymal transition in breast cancers.

The recurrence and metastasis in breast cancer within 3 years after the chemotherapies or surgery leads to poor prognosis with approximately 1-year overall survival. Large-scale scanning research studies have shown that taking lipid-lowering drugs may assist to reduce the risk of death from many cancers, since cholesterol in lipid rafts are essential for maintain integral membrane structure and functional signaling regulation. In this study, we examined five lipid-lowering drugs: swertiamarin, gemfibrozil, clofibrate, bezafibrate, and fenofibrate in triple-negative breast cancer, which is the most migration-prone subtype. Using human and murine triple-negative breast cancer cell lines (Hs 578 t and 4 T1), we found that fenofibrate displays the highest potential in inhibiting the colony formation, wound healing, and transwell migration. We further discovered that fenofibrate reduces the activity of pro-metastatic enzymes, matrix metalloproteinases (MMP)-9 and MMP-2. In addition, epithelial markers including E-cadherin and Zonula occludens-1 are increased, whereas mesenchymal markers including Snail, Twist and α-smooth muscle actin are attenuated. Furthermore, we found that fenofibrate downregulates ubiquitin-dependent GDF-15 degradation, which leads to enhanced GDF-15 expression that inhibits cell migration. Besides, nuclear translocation of FOXO1 is also upregulated by fenofibrate, which may responsible for GDF-15 expression. In summary, fenofibrate with anti-cancer ability hinders TNBC from migration and invasion, and may be beneficial to repurposing use of fenofibrate.

Transcriptomics identifies blunted immunomodulatory effects of vitamin D in people with multiple sclerosis.

Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). However, the immune effects of vitamin D in people with MS are not well understood. We analyzed transcriptomic datasets generated by RNA sequencing of immune cell subsets (CD4+, CD8+ T cells, B cells, monocytes) from 33 healthy controls and 33 untreated MS cases. We utilized a traditional bioinformatic pipeline and weighted gene co-expression network analysis (WGCNA) to determine genes and pathways correlated with endogenous vitamin D. In controls, CD4+ and CD8+ T cells had 1079 and 1188 genes, respectively, whose expressions were correlated with plasma 25-hydroxyvitamin D level (P < 0.05). Functional enrichment analysis identified association with TNF-alpha and MAPK signaling. In CD4+ T cells of controls, vitamin D level was associated with expression levels of several genes proximal to multiple sclerosis risk loci (P = 0.01). Genes differentially associated with endogenous vitamin D by case-control status were enriched in TNF-alpha signaling via NF-κB. WGCNA suggested a blunted response to vitamin D in cases relative to controls. Collectively, our findings provide further evidence for the immune effects of vitamin D, and demonstrate a differential immune response to vitamin D in cases relative to controls, highlighting a possible mechanism contributing to MS pathophysiology.

Neutropaenia complications from Ocrelizumab and Rituximab treatment.

Ocrelizumab is an anti-CD20 monoclonal antibody (mAb) that has been shown in phase 3 clinical trials to reduce relapses and disease progression in multiple sclerosis (MS) patients. Prior to the approval of ocrelizumab, rituximab, a chimeric anti-CD20 mAb was used to treat MS. Rituximab is still used to treat MS in many countries outside of Australia and remains mainstay of treatment of many non-MS neuroimmunological and systemic inflammatory diseases. Rituximab is currently used in neuromyelitis optica spectrum disorder (NMOSD) and autoimmune encephalitis, in addition to its widespread usage in hematological malignancies and systemic inflammatory diseases. Ocrelizumab is currently approved in Australia for treatment of relapsing-remitting MS (RRMS). Neutropaenia is a rare complication of both ocrelizumab and rituximab treatment. This case series reports 12 patients who have experienced neutropaenia following ocrelizumab or rituximab treatment and aims to characterize the clinical parameters of neutropaenia experienced by these patients, including the severity and duration of neutropaenia, length of hospital admission, the types of subsequent infections experienced and types of treatment necessary before patients reached count recovery. The unpredictability of neutropaenia and potential for serious infections highlight the need for continued hematological monitoring for patients on B-cell depleting therapies and calls for careful patient counselling to provide guidance on whether to continue such therapies in patients who have experienced related neutropaenia.

Inhibitory Effects of Urolithins, Bioactive Gut Metabolites from Natural Polyphenols, against Glioblastoma Progression.

We previously reported that proinflammatory cytokines, particularly tumor necrosis factor (TNF)-α, promoted tumor migration, invasion, and proliferation, thus worsening the prognosis of glioblastoma (GBM). Urolithins, the potent metabolites produced by the gut from pomegranate polyphenols, have anticancer properties. To develop an effective therapy for GBM, this study aimed to study the effects of urolithins against GBM. Urolithin A and B significantly reduced GBM migration, reduced epithelial-mesenchymal transition, and inhibited tumor growth. Moreover, urolithin A and B inhibited TNF-α-induced vascular cell adhesion molecule (VCAM)-1 and programmed death ligand 1 (PD-L1) expression, thereby reducing human monocyte (HM) binding to GBM cells. Aryl hydrocarbon receptor (AhR) level had higher expression in patients with glioma than in healthy individuals. Urolithins are considered pharmacological antagonists of AhR. We demonstrated that the inhibition of AhR reduced TNF-α-stimulated VCAM-1 and PD-L1 expression. Furthermore, human macrophage condition medium enhanced expression of PD-L1 in human GBM cells. Administration of the AhR antagonist attenuated the enhancement of PD-L1, indicating the AhR modulation in GBM progression. The modulatory effects of urolithins in GBM involve inhibiting the Akt and epidermal growth factor receptor pathways. The present study suggests that urolithins can inhibit GBM progression and provide valuable information for anti-GBM strategy.

Correlation Between Lipoprotein-Related Phospholipase A2 and Metabolic Syndrome.

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been recognized as a valuable biomarker for identifying the risk of cardiovascular diseases and inflammation. Furthermore, there is strong evidence to suggest that metabolic syndrome is closely associated with chronic inflammation. Accordingly, the present study endeavors to examine the potential correlation between metabolic syndrome and the levels of Lp-PLA2. Methods: To explore the relationship between Lp-PLA2 levels and metabolic syndrome, and to establish the predictive cut-off value of Lp-PLA2, a retrospective analysis was conducted using medical data from a sample of 3549 Chinese adults (comprising 2182 men and 1367 women) aged between 18 and 50 years, who had undergone health check-ups. In addition, the study also sought to investigate any potential differences in Lp-PLA2 levels based on sex and age. Results: The analysis of the data indicated that participants had a mean age of 44.2 years, a mean Lp-PLA2 level of 589 IU/L, and a metabolic syndrome prevalence of 22%. Lp-PLA2 levels were significantly different between males and females, and a significant correlation was observed between Lp-PLA2 levels and clinical and metabolic characteristics, including BMI, cholesterol, and triglycerides. Interestingly, Lp-PLA2 demonstrated potential as an indicator of metabolic syndrome, particularly in females, despite other biomarkers, such as TG/HDL-C and WHR, exhibiting better area under the curve. Conclusion: Our findings suggest that Lp-PLA2 may serve as a useful biomarker for identifying individuals at risk of developing metabolic syndrome, particularly in females. Further research is needed to explore the potential of Lp-PLA2 as a diagnostic and therapeutic target for metabolic syndrome.

Imperatorin ameliorates pulmonary fibrosis via GDF15 expression.

Background: Pulmonary fibrosis features in damaged pulmonary structure or over-produced extracellular matrix and impaired lung function, leading to respiratory failure and eventually death. Fibrotic lungs are characterized by the secretion of pro-fibrotic factors, transformation of fibroblasts to myofibroblasts, and accumulation of matrix proteins. Hypothesis/purpose: Imperatorin shows anti-inflammatory effects on alveolar macrophages against acute lung injury. We attempt to evaluate the properties of imperatorin on the basis of fibroblasts. Methods: In in vitro, zymosan was introduced to provoke pro-fibrotic responses in NIH/3T3 or MRC-5 pulmonary fibroblasts. Imperatorin was given for examining its effects against fibrosis. The mice were stimulated by bleomycin, and imperatorin was administered to evaluate the prophylactic potential in vivo. Results: The upregulated expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen protein due to zymosan introduction was decreased by imperatorin in fibroblasts. Zymosan induced the activity of transglutaminase 2 (TGase2) and lysyl oxidase (LOX), which was also inhibited by the administration of imperatorin. Imperatorin alone enhanced sirtuin 1 (SIRT1) activity and growth differentiation factor 15 (GDF15) secretion in fibroblasts via LKB1/AMPK/CREB pathways. In addition, GDF15 exerted a beneficial effect by reducing the protein expression of CTGF, α-SMA, and collagen and the activities of TGase and LOX. Moreover, orally administered imperatorin showed prophylactic effects on bleomycin-induced pulmonary fibrosis in mice. Conclusion: Imperatorin reduces fibrotic marker expression in fibroblasts and also increases GDF15 secretion via the LKB1/AMPK/CREB pathway, attenuating pro-fibrotic responses in vitro. Imperatorin also alleviates pulmonary fibrosis induced by bleomycin in vivo.

Hyperspectral screen-image-synthesis meter with scattering-noise suppression.

The screen image synthesis (SIS) meter was originally proposed as a high-speed measurement tool, which fused the measured data from multiple sample-rotational angles to produce a whole-field measurement result. However, it suffered from stray light noise and lacked the capability of spectrum measurement. In this study, we propose an SIS system embedded with a snapshot hyperspectral technology, which was based on a dispersion image of the sparse sampling screen (SSS). When a photo was captured, it was transformed and calibrated to hyperspectral data at a specific sample-rotational angle. After the hyperspectral data in all sample-rotational angles were captured, an SIS image-fusion process was then applied to get the whole field hyperspectral data. By applying SSS to the SIS meter, we not only create a screen image synthesis hyperspectral meter but also effectively address the issue of stray-light noise. In the experiment, we analyze its correctness by comparing the hyperspectral value with a one-dimensional spectrum goniometer (ODSG). We also show the 2D color temperature coefficient distribution and compare it with the ODSG. Experimental results also demonstrate the feasibility in terms of both spectrum distribution meter and color coefficient temperature distribution meter.

Association of low serum ferritin levels with augmentation in patients with restless legs syndrome: A systematic review and meta-analysis.

BACKGROUND: Augmentation of restless legs syndrome (RLS) is an iatrogenic side effect induced by dopaminergic agents, and it is a major cause of therapeutic failure. Iron deficiency is a risk factor for RLS, but its effects on the development of RLS augmentation are unclear. This meta-analysis aimed to elucidate the association between serum ferritin and RLS augmentation. METHODS: We searched the PubMed, Cochrane Library, Embase, ClinicalKey, ScienceDirect, and ProQuest databases for studies comparing the serum ferritin levels of patients with augmented RLS and nonaugmented RLS. A meta-analysis based on a random-effects model was conducted. Levodopa equivalent dose (LED), International Restless Legs Study Group Severity Rating Scale (IRLS), and serum hemoglobin levels were also analyzed. RESULTS: Six observational studies fulfilled the eligibility criteria of this meta-analysis. A total of 220 RLS patients with augmentation and 687 RLS patients without augmentation were included. The results revealed that augmented RLS was significantly associated with low serum ferritin levels (p = 0.002), high LEDs (p = 0.026), and nonsignificantly associated with high IRLS scores (p = 0.227). CONCLUSIONS: A low serum ferritin level is associated with RLS augmentation. For patients with RLS who are iron deficient, iron supplements can not only relieve their fundamental RLS symptoms but also lower the risk of RLS augmentation. Moreover, non-dopminergic agents should be considered as the first-line treatment for patients with persistent low serum ferritin levels or those with moderate to severe RLS to prevent augmentation.

Association between subclinical epileptiform discharge and the behavioral and psychological symptoms in patients with Alzheimer's dementia.

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are highly prevalent in patients with Alzheimer's disease (AD), causing burdens on caregivers. Behavioral and psychological symptoms of dementia and subclinical epileptiform discharge (SED) increased with the disease course of AD. However, the interaction between them was still unknown. The present study aimed to evaluate the associations between SED and BPSD. METHODS/DESIGN: Patients with AD from Kaohsiung Municipal Ta-tung Hospital were included in this study. International 10-20 system scalp electroencephalography (EEG) for 13 min was performed to detect SED. Behavioral and psychological symptoms of dementia was assessed by neuropsychiatric inventory (NPI) questionnaires. The occurrence of BPSD subsyndromes was compared between patients with and without SED. RESULTS: Two hundred sixty-three adult patients qualified for the inclusion criteria and were enrolled in this study. The mean age of patients was 80.2 years, and approximately 62% were women. 17.1% of patients showed SED on EEG. Apathy was the most commonly reported BPSD subsyndrome in this cohort. There was no significant difference in the prevalence of BPSD between patients with and without SED. (75.6% vs. 67.4%, p = 0.2806). However, the NPI score of irritability subsyndrome was significantly higher in the SED (+) group (2.6 ± 3.7 vs. 1.2 ± 2.7, p = 0.0028). In addition, subclinical epileptiform discharge in the frontal lobe was associated with a considerably higher occurrence of hyperactivity subsyndrome, including irritability. CONCLUSIONS: SED may not be a direct cause of BPSD, but the presence of SED may affect the manifestation of BPSD.