Comparison of Synergistic Sedation with Midazolam and Propofol Versus Midazolam and Pethidine in Colonoscopies: A Prospective, Randomized Controlled Study.

Colonoscopy is a key procedure for the early detection of colorectal cancer. Despite its importance, the discomfort associated with colonoscopy often requires sedation, and the ideal sedation regimen remains to be determined. In this prospective randomized controlled trial, patients scheduled for colonoscopy were randomly assigned to two different sedation protocols. Group A received a combination of midazolam and propofol, while group B was given midazolam and pethidine. The study analyzed data from 51 patients, with 23 in group A and 28 in group B. The incidence of adverse events was similar across both groups. Additionally, no significant differences were observed in cecal intubation times or total procedure durations. Notably, group A had a lower frequency of required postural changes (1.0±.7 vs. 1.5±0.7, p=0.02) and a reduced rate of manual compression (52.2% vs. 82.1%, p=0.02). There were no significant differences between the groups regarding subjective pain or overall satisfaction. Both sedation regimens were found to be safe and effective. The midazolam and propofol combination was associated with a smoother procedure, evidenced by fewer postural adjustments and less manual compression needed during colonoscopy.

Negative Effect of the Calendering Process on the Interphase Formation and Electrochemical Behavior of Reduced Graphene Oxide Electrodes.

Many studies on electrode material development for rechargeable batteries have focused on improving the intrinsic physicochemical and electrochemical properties of active materials, but the electrochemical performances of batteries are exhibited by the overall electrode unit consisting of active materials, conductive additives, and a binder. Additionally, the electrodes have undergone an essential calendering process to enhance the physical contact between those components. Therefore, the electrochemical behavior and performance of a cell should be analyzed at the electrode level, as the inherent properties of active materials might be changed in electrode preparation, including the calendaring process and real-operating environments. In this study, we aimed to understand the electrochemical properties of the reduced graphene oxide (RGO)-containing electrodes rather than the RGO-active materials by studying the changes in the RGO electrode before and after the calendering process. Specifically, the study investigates the effect of the calendering process on the electrochemically active interphase formation and electrochemical properties of the RGO electrode. We found that the calendering process deteriorates the electrochemical properties of RGO electrodes by impeding enough electrolyte wetting, limiting the formation of thin and stable solid-electrolyte interphase, and leaving unreacted RGO sheets. Additional experiments with carbon-coated silicon/RGO composite electrodes demonstrate that after the calendering process, the sequential participation of Si/C particles in the electrochemical reaction resulted in much more severe capacity degradation over repeated cycling processes. The studies suggest that fine-controlling the number of RGO sheets and maintaining enough distance between those sheets even after the calendering process are required for the utilization of RGO in rechargeable batteries.

Evaluation of healing after arthroscopic repair of lateral meniscal tears around the popliteal hiatus.

BACKGROUND: The popliteal hiatus stabilizes the lateral meniscus (LM). Variable failure rates for LM repairs have been reported in knees with lateral meniscal tears (LMTs), which may be attributable to low vascularity around the popliteal hiatus. An effective repair method is essential to enhance the biological healing and stability of LMTs around the popliteal hiatus. HYPOTHESIS: Arthroscopic repair of LMTs, including the popliteus tendon around the popliteal hiatus, is expected to produce a low reoperation rate and effective treatment, both clinically and radiographically. MATERIAL AND METHODS: From June 2011 to August 2020, 93 patients (mean age 27.9 ± 13.5 years) who underwent arthroscopic repair of LMTs including the popliteus tendon around the popliteal hiatus were enrolled. Patients with LMTs were divided into three groups: isolated LMTs, discoid LMTs, and LMTs with ACL injury. Patients had a minimum clinical follow-up of 2 years (mean 37.9 ± 19.3 months) and Tegner activity, Lysholm knee, and Hospital for Special Surgery (HSS) scores were evaluated for all patients. The widths of the popliteal hiatus and LM extrusion were measured on the sagittal and coronal planes using preoperative and postoperative magnetic resonance imaging (MRI). RESULTS: The Tegner activity (2.6 ± 1.2-4.5 ± 1.3), Lysholm (67.9 ± 14.2-88.1 ± 6.4), and HSS scores (79.8 ± 11.5-93.7 ± 5.1) were significantly improved in all knees (p < 0.001). The width of the popliteal hiatus measured on MRI was significantly decreased, when comparing the preoperative and postoperative MRI for all knees (sagittal plane, 2.9 ± 1.4-1.5 ± 0.5 mm; coronal plane, 3.8 ± 2.5 to 1.9 ± 1.0 mm) (p < 0.05). The LM extrusion measured on the sagittal plane of postoperative MRI was also significantly reduced after arthroscopic repair (24.8 ± 3.1-23.7 ± 2.8 mm) (p = 0.001). Five reoperations (5/93, 5.3%) were performed, suggesting a clinical failure. CONCLUSION: Arthroscopic repair of isolated, discoid and post-traumatic LMTs including the popliteus tendon around the popliteal hiatus, is an effective surgical treatment for LM stabilization. LEVEL OF EVIDENCE: Level IV, retrospective series.

Real-world application of a 3D deep learning model for detecting and localizing cerebral microbleeds.

BACKGROUND: Detection and localization of cerebral microbleeds (CMBs) is crucial for disease diagnosis and treatment planning. However, CMB detection is labor-intensive, time-consuming, and challenging owing to its visual similarity to mimics. This study aimed to validate the performance of a three-dimensional (3D) deep learning model that not only detects CMBs but also identifies their anatomic location in real-world settings. METHODS: A total of 21 patients with 116 CMBs and 12 without CMBs were visited in the neurosurgery outpatient department between January 2023 and October 2023. Three readers, including a board-certified neuroradiologist (reader 1), a resident in radiology (reader 2), and a neurosurgeon (reader 3) independently reviewed SWIs of 33 patients to detect CMBs and categorized their locations into lobar, deep, and infratentorial regions without any AI assistance. After a one-month washout period, the same datasets were redistributed randomly, and readers reviewed them again with the assistance of the 3D deep learning model. A comparison of the diagnostic performance between readers with and without AI assistance was performed. RESULTS: All readers with an AI assistant (reader 1:0.991 [0.930-0.999], reader 2:0.922 [0.881-0.905], and reader 3:0.966 [0.928-0.984]) tended to have higher sensitivity per lesion than readers only (reader 1:0.905 [0.849-0.942], reader 2:0.621 [0.541-0.694], and reader 3:0.871 [0.759-0.935], p = 0.132, 0.017, and 0.227, respectively). In particular, radiology residents (reader 2) showed a statistically significant increase in sensitivity per lesion when using AI. There was no statistically significant difference in the number of FPs per patient for all readers with AI assistant (reader 1: 0.394 [0.152-1.021], reader 2: 0.727 [0.334-1.582], reader 3: 0.182 [0.077-0.429]) and reader only (reader 1: 0.364 [0.159-0.831], reader 2: 0.576 [0.240-1.382], reader 3: 0.121 [0.038-0.383], p = 0.853, 0.251, and 0.157, respectively). Our model accurately categorized the anatomical location of all CMBs. CONCLUSIONS: Our model demonstrated promising potential for the detection and anatomical localization of CMBs, although further research with a larger and more diverse population is necessary to establish clinical utility in real-world settings.

Polarized Raman spectroscopy study of CVD-grown Cr2S3 flakes: unambiguous identification of phonon modes.

We report a systematic Raman spectroscopy investigation of chemical vapor deposited 2D nonlayered Cr2S3, with both linearly and circularly polarized light over a wide temperature range (5-300 K). Temperature-dependent Raman spectra exhibit a good linear relationship between the peak positions of the phonon modes and temperature. Angle-resolved polarized Raman spectra reveal the polarization-dependent optical response of in-plane and out-of-plane phonon modes. Helicity-dependent Raman investigations complete definite assignment of all the phonon modes observed in the Raman spectra of 2D nonlayered Cr2S3 by the optical selection rule based on a Raman tensor. Our work realizes clear phonon mode identification over a wide temperature range for the emerging material 2D Cr2S3, an important representative of nonlayered 2D system with unique properties for optoelectronic and spintronic applications.

Quality Characteristics of Meat Analogs through the Incorporation of Textured Vegetable Protein and Tenebrio molitor Larvae in the Presence of Transglutaminase.

Alternative protein sources with greater nutritional value and a lower environmental footprint have recently attracted interest in the production of meat substitutes. However, it is required that these alternatives mimic the texture and structure of meat. This study investigated varying ratios of textured vegetable proteins (TVP) to Tenebrio molitor larvae (brown mealworm; TM) with the addition of transglutaminase (TG) to determine the quality characteristics of these emulsions. The results demonstrated low protein solubility of the emulsions as TVP content increased. Furthermore, when the proportion of TM was high, the TG-treated emulsion had a low pH. Additionally, when there was a high TM ratio to TVP in the TG treatment, the emulsions demonstrated better thermal stability and water holding capacity. Regarding the rheological properties of the emulsion, both the frequency-dependent storage modulus (G') and loss modulus (G'') increased as the proportion of TVP in the emulsion increased with and without the addition of TG. Differential scanning calorimetry analyses demonstrated two protein denaturation peaks in all treatments, with high peak temperatures for both treatments with a high proportion of TM. The hardness and chewiness of the emulsion were highest in the treatment (T6 and T8) with TG, and the gumminess of the emulsion was greatest when TM only or when equal ratios of TVP and TM were treated with TG, respectively. In conclusion, the addition of TM to TVP with TG improves the overall texture of the protein mixture, making it a suitable meat alternative.

Biomimetic Scaffolds of Calcium-Based Materials for Bone Regeneration.

Calcium-based materials, such as calcium carbonate, calcium phosphate, and calcium silicate, have attracted significant attention in biomedical research, owing to their unique physicochemical properties and versatile applications. The distinctive characteristics of these materials, including their inherent biocompatibility and tunable structures, hold significant promise for applications in bone regeneration and tissue engineering. This review explores the biomedical applications of calcium-containing materials, particularly for bone regeneration. Their remarkable biocompatibility, tunable nanostructures, and multifaceted functionalities make them pivotal for advancing regenerative medicine, drug delivery system, and biomimetic scaffold applications. The evolving landscape of biomedical research continues to uncover new possibilities, positioning calcium-based materials as key contributors to the next generation of innovative biomaterial scaffolds.

Comparison of Tumor Microenvironments between Primary Tumors and Lymph Node Metastases in Head and Neck Squamous Cell Carcinoma and Their Predictive Role in Immune Checkpoint Inhibitor Treatment.

The relationship between tumor microenvironments (TMEs) of regional lymph node metastases (LNMs) and primary tumors in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study compared tumor-infiltrating lymphocytes (TILs) and the immune phenotype (IP), characterized by spatial TIL distribution, between primary tumors and LNMs. Twenty-one HNSCC patients with regional LNM who received immune checkpoint inhibitors (ICIs) were included. A paired comparative analysis of TIL densities and IP between primary tumors and LNMs revealed no significant difference or correlation between TIL densities in primary tumors and LNMs. Their IPs were discordant in 12 patients (57.1%). Patients with high intratumoral TIL exhibited longer progression-free survival (PFS) than those with low intratumoral TIL in both primary tumors (median, 5.2 vs. 1.3 months, p = 0.003) and LNMs (median, 30.2 vs. 1.3 months, p = 0.012). Patients with inflamed IP exhibited longer PFS than those with non-inflamed IP in both primary tumors (median, 4.5 vs. 1.3 months, p = 0.043) and LNMs (median, 4.1 vs. 1.3 months, p = 0.037). Given the lack of correlation in TIL densities, the discrepancies in IP, and the predictive value of both TMEs, evaluating the TMEs of both primary tumors and LNMs may be beneficial for the precise use of ICIs in HNSCC. There was a significant discordance between the TME of primary tumors and LNMs, with implications in survival outcomes. Therefore, evaluating the TME of both the primary tumor and LNM could be beneficial for the precise use of ICIs in HNSCC.

Bimekizumab efficacy and safety in Korean patients with moderate to severe plaque psoriasis: A phase 3, randomized, placebo-controlled, double-blinded study.

Bimekizumab treatment has demonstrated significant improvements in clinical outcomes in patients with moderate to severe plaque psoriasis; however, studies so far have focused on predominantly White patient populations from North America and Europe, with one smaller study in a Japanese population. Here, clinical responses, safety, and tolerability of bimekizumab treatment in Korean patients are reported. Korean patients with moderate to severe plaque psoriasis were randomized to bimekizumab 320 mg every 4 weeks (Q4W) or placebo Q4W to week 16. Co-primary efficacy end points were achievement of ≥90% improvement from baseline in the Psoriasis Area and Severity Index (PASI 90) and Investigator's Global Assessment score of 0/1 (clear/almost clear) at week 16. Secondary efficacy end points included achievement of PASI 75 at week 4 and Dermatology Life Quality Index 0/1 at week 16. Safety outcomes were also assessed. Statistical analysis of the co-primary efficacy end points was performed using a type I error rate, at a two-sided α level of 0.05. Overall, 47 Korean patients were randomized to treatment (bimekizumab: 32, placebo: 15). At week 16, bimekizumab-treated patients had significantly higher clinical responses versus placebo-treated patients (PASI 90: 81.3% vs. 0%; IGA 0/1: 87.5% vs. 0%, p < 0.001 for both). Bimekizumab showed a rapid onset of clinical response, with 75.0% of patients achieving PASI 75 by week 4 (0% in placebo patients [nominal p < 0.001]). A higher proportion of bimekizumab-treated patients achieved DLQI 0/1 at week 16 (46.9% vs. 6.7% in placebo patients, nominal p = 0.007), indicating greater improvements in health-related quality of life (HRQoL) following bimekizumab treatment. Bimekizumab was well-tolerated in Korean patients, with no new safety signals identified. Treatment with bimekizumab led to rapid improvements in clinical responses and HRQoL versus placebo in Korean patients, consistent with responses in global populations. These findings suggest that bimekizumab is an effective and well-tolerated treatment option in Korean patients with psoriasis.

The toxic effects of polystyrene microplastic/nanoplastic particles on retinal pigment epithelial cells and retinal tissue.

The increasing use of contact lenses, artificial tears, and anti-vascular endothelial growth factor (anti-VEGF) drug injections for age-related macular degeneration has heightened the likelihood of eye exposure to microplastic particles. Extensive research has established that microplastic particles can induce oxidative stress on the ocular surface, resulting in damage. However, the impact of these particles on the retina remains unclear. Therefore, this study investigated whether microplastics/nanoplastics (MPs/NPs) cause retinal damage. In vitro human retinal pigment epithelial (RPE) cells were exposed to polystyrene MPs and NPs for 48 h. Assessment of cell viability using WST-8; evaluation of TNF-α and IL-1ß expression; observation of cell morphology and particle invasion via TEM; measurement of ROS levels using the DCFDA reagent; and western blot analysis of SOD2, FIS1, Drp1, and LC3B expression were conducted. In vivo experiments involved intravitreal injection of MPs/NPs in rats, followed by retinal H&E staining 24 h later and evaluation of TNF-α and IL-1ß expression. Results indicated that exposure to MPs did not significantly alter RPE cell viability, whereas exposure to NPs led to a noticeable decrease. TEM images revealed NPs' penetration into cells, causing increased oxidative stress (SOD2), mitochondrial fission (FIS1, Drp1), and mitochondrial autophagy (LC3B). In vivo experiments demonstrated an increase in inflammatory cells in retinal tissues exposed to NPs, along with elevated levels of TNF-α and IL-1ß. Conclusively, both MPs and NPs impact the retina, with NPs displaying greater toxicity. NPs significantly elevate ROS levels in the retina and induce mitochondrial fission and mitophagy in RPE cells compared to MPs.

Laser-responsive erastin-loaded chondroitin sulfate nanomedicine targeting CD44 and system xc- in liver cancer: A non-ferroptotic approach.

Erastin, a ferroptosis-inducing system xc- inhibitor, faces clinical challenges due to suboptimal physicochemical and pharmacokinetic properties, as well as relatively low potency and off-target toxicity. Addressing these, we developed ECINs, a novel laser-responsive erastin-loaded nanomedicine utilizing indocyanine green (ICG)-grafted chondroitin sulfate A (CSA) derivatives. Our aim was to improve erastin's tumor targeting via CSA-CD44 interactions and enhance its antitumor efficacy through ICG's photothermal and photodynamic effects in the laser-on state while minimizing off-target effects in the laser-off state. ECINs, with their nanoscale size of 186.7 ± 1.1 nm and high erastin encapsulation efficiency of 93.0 ± 0.8%, showed excellent colloidal stability and sustained drug release up to 120 h. In vitro, ECINs demonstrated a mechanism of cancer cell inhibition via G1-phase cell cycle arrest, indicating a non-ferroptotic action. In vivo biodistribution studies in SK-HEP-1 xenograft mice revealed that ECINs significantly enhanced tumor distribution of erastin (1.9-fold greater than free erastin) while substantially reducing off-target accumulation in the lungs and spleen by 203-fold and 19.1-fold, respectively. Combined with laser irradiation, ECINs significantly decreased tumor size (2.6-fold, compared to free erastin; 2.4-fold, compared to ECINs without laser irradiation) with minimal systemic toxicity. This study highlights ECINs as a dual-modality approach for liver cancer treatment, demonstrating significant efficacy against tumors overexpressing CD44 and system xc-.

Enhanced Hybrid Nanogenerator Based on PVDF-HFP and PAN/BTO Coaxially Structured Electrospun Nanofiber.

Nanogenerators have garnered significant interest as environmentally friendly and potential energy-harvesting systems. Nanogenerators can be broadly classified into piezo-, tribo-, and hybrid nanogenerators. The hybrid nanogenerator used in this experiment is a nanogenerator that uses both piezo and tribo effects. These hybrid nanogenerators have the potential to be used in wearable electronics, health monitoring, IoT devices, and more. In addition, the versatility of the material application in electrospinning makes it an ideal complement to hybrid nanogenerators. However, despite their potential, several experimental variables, biocompatibility, and harvesting efficiency require improvement in the research field. In particular, maximizing the output voltage of the fibers is a significant challenge. Based on this premise, this study aims to characterize hybrid nanogenerators (HNGs) with varied structures and material combinations, with a focus on identifying HNGs that exhibit superior piezoelectric- and triboelectric-induced voltage. In this study, several HNGs based on coaxial structures were fabricated via electrospinning. PVDF-HFP and PAN, known for their remarkable electrospinning properties, were used as the primary materials. Six combinations of these two materials were fabricated and categorized into homo and hetero groups based on their composition. The output voltage of the hetero group surpassed that of the homo group, primarily because of the triboelectric-induced voltage. Specifically, the overall output voltage of the hetero group was higher. In addition, the combination group with the most favorable voltage characteristics combined PVDF-HFP@PAN(BTO) and PAN hollow, boasting an output voltage of approximately 3.5 V.

Clinical Manifestations, Macrolide Resistance, and Treatment Utilization Trends of Mycoplasma pneumoniae Pneumonia in Children and Adolescents in South Korea.

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

Blockade of forkhead box protein O1 signaling alleviates primary sclerosing cholangitis-induced sarcopenia in mice model.

AIMS: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that affects the hepatic bile ducts, leading to hepatic inflammation and fibrosis. PSC can also impact skeletal muscle through the muscle-liver axis, resulting in sarcopenia, a complication characterized by a generalized loss of muscle mass and strength. The underlying mechanisms and therapy of PSC-induced sarcopenia are not well understood, but one potential regulator is the transcription factor forkhead box protein O1 (FOXO1), which is involved in the ubiquitin proteasome system. Thus, the aim of this study is to assess the pharmacological potential of FOXO1 inhibition for treating PSC-induced sarcopenia. MATERIALS AND METHODS: To establish diet-induced PSC model, we provided mice with a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet for 4 weeks. Mice were intramuscularly injected with AS1842856 (AS), a FOXO1 inhibitor, at a dose of 3.5 mg/kg twice a week for last two weeks. C2C12 myotubes with cholic acid (CA) or deoxycholic acid (DCA) were treated with AS. KEY FINDINGS: We observed a decrease in muscle size and performance in DDC-fed mice with upregulated expression of FOXO1 and E3 ligases such as ATROGIN1 and MuRF1. We found that myotube diameter and MyHC protein level were decreased by CA or DCA in C2C12 myotubes, but treatment of AS reversed these reductions. We observed that intramuscular injection of AS effectively mitigates DDC diet-induced sarcopenia in a rodent PSC model. SIGNIFICANCE: Our study suggests that a FOXO1 inhibitor could be a potential leading therapeutic drug for relieving PSC-induced sarcopenia.

Efficacy of RCI001 as a Therapeutic Candidate in a Primary Sjögren Syndrome Mouse Model.

PURPOSE: The aim of this study was to investigate the efficacy of RCI001 (RCI) in a mouse model of primary Sjögren syndrome. METHODS: Eight 12-week-old NOD.B10-H2b mice were used in this study. All experimental animals were randomly divided into phosphate-buffered saline (PBS) and RCI groups in NOD.B10-H2b mice. The eyes of mice were topically treated with PBS or RCI twice a day for a week. Ocular surface staining (OSS) and tear secretion were compared between before and after treatment. The transcript levels of inflammatory cytokines and nicotinamide adenine dinucleotide phosphate oxidase (NOX) in the conjunctiva and cornea (CC) and lacrimal gland were assayed. In addition, immunofluorescence staining of the conjunctiva was assessed. RESULTS: The RCI group showed significant clinical improvement in OSS and tear secretion after 1 week of treatment compared with the baseline (both P < 0.001) and showed better improvement in OSS and tear secretion than the PBS group after 1 week of treatment (both P < 0.05). The levels of IL-1ß and IL-17 in CC and IL-6 in the lacrimal gland were also significantly reduced in the RCI group compared with the PBS group (each P < 0.05). Transcript levels of NOX2 and NOX4 were also significantly reduced in CC of the RCI group compared with those of the PBS group (P < 0.05). The RCI group also resulted in lower conjunctival expression of oxidative stress markers (4-hydroxy-2-nonenal, hexanoyl-lysine, and NOX4) than the PBS group. CONCLUSIONS: Topical RCI001 demonstrated excellent therapeutic efficacy in a mouse model of primary Sjögren syndrome by inhibiting inflammation and oxidative stress.

The extracellular vesicle of depressive patient-derived Escherichia fergusonii induces vagus nerve-mediated neuroinflammation in mice.

BACKGROUND: Gut microbiota dysbiosis is closely associated with psychiatric disorders such as depression and anxiety (DA). In our preliminary study, fecal microbiota transplantation from volunteers with psychological stress and subclinical symptoms of depression (Vsd) induced DA-like behaviors in mice. Escherichia fergusonii (Esf) was found to be more abundant in the feces of Vsd compared to healthy volunteers. Therefore, we investigated the effect of Esf on DA-like behavior and neuroinflammation in mice with and without celiac vagotomy. METHODS AND RESULTS: Orally gavaged Esf increased DA-like behaviors, tumor necrosis factor (TNF)-α, and toll-like receptor-4 (TLR4) expression, and NF-κB+Iba1+ and lipopolysaccharide (LPS)+Iba1+ cell populations, while decreasing serotonin, 5-HT1A receptor, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus and prefrontal cortex. However, celiac vagotomy attenuated Esf-induced DA-like behavior and neuroinflammation. Orally gavaged extracellular vesicle (EV) from Vsd feces (vfEV) or Esf culture (esEV) induced DA-like behavior and inflammation in hippocampus, prefrontal cortex and colon. However, celiac vagotomy attenuated vfEV- or esEV-induced DA-like behaviors and inflammation in the brain alone, while vfEV- or esEV-induced blood LPS and TNF-α levels, colonic TNF-α expression and NF-κB-positive cell number, and fecal LPS level were not. Although orally gavaged fluorescence isothiocyanate-labeled esEV was translocated into the blood and hippocampus, celiac vagotomy decreased its translocation into the hippocampus alone. CONCLUSIONS: esEVs may be translocated into the brain via the vagus nerve and bloodstream, subsequently inducing TNF-α expression and suppressing serotonin, its receptor, and BDNF expression through the activation of TLR4-mediated NF-κB signaling, thereby contributing to DA pathogenesis.

Impact of cross-reactivity and herd immunity on SARS-CoV-2 pandemic severity.

Public health systems reported low mortality from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in East Asia, in low-income countries, and for children during the first year of the SARS-CoV-2 pandemic. These reports led commentators to suggest that cross-reactive immunity from prior exposure to other pathogens reduced fatality risk. Resolution of initial infection waves also contributed to speculation that herd immunity prevented further waves prior to vaccination. Serology instead implied that immunity was too limited to achieve herd immunity and that there was little impact from cross-reactive protection. Paediatric deaths exceeded those from influenza, with higher age-specific fatality risk in lower-income nations and similar fatality risk in East Asia compared with demographically similar regions. Neither pre-outbreak exposure to related pathogens nor immunity induced by initial infection waves are necessarily a reliable response to future pathogen outbreaks. Preparedness for future pathogen outbreaks should instead focus on strategies such as voluntary behavioural changes, nonpharmaceutical interventions, and vaccination.

Exposure to per- and polyfluoroalkyl substances and age-related macular degeneration in U.S. middle-aged and older adults.

Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005-2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend = 0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.

Solution-Processed Thick Hole-Transport Layer for Reliable Quantum-Dot Light-Emitting Diodes Based on an Alternatingly Doped Structure.

The operating lifetime of quantum-dot light-emitting diodes (QLED) is a bottleneck for commercial display applications. To enhance the operational stability of QLEDs, we developed a robust solution-processed highly conductive hole-transport-layer (HTL) structure, which enables a thick HTL structure to mitigate the electric field. An alternating doping strategy, which involves multiple alternating stacks of N4,N4'-di(naphthalen-1-yl)-N4,N4'-bis(4-vinylphenyl)biphenyl-4,4'-diamine and phosphomolybdic acid layers, could provide significantly improved conductivity; more specifically, the 90 nm-thick alternatingly doped HTL exhibited higher conductivity than the 45 nm-thick undoped HTL. Therefore, when applied to a QLED, the increase in the thickness of the alternatingly doped HTL increased device reliability. As a result, the lifetime of the QLED with a thick, alternatingly doped HTL was 48-fold higher than that of the QLED with a thin undoped HTL. This alternating doping strategy provides a new paradigm for increasing the stability of solution-based optoelectronic devices in addition to QLEDs.

Predictive value of early dynamic changes of NLR and PLR for the efficacy of immune checkpoint inhibitor in head and neck squamous cell carcinoma.

OBJECTIVE: We analyzed the predictive value of dynamic changes in neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors (ICIs). STUDY DESIGN: A total of 104 patients with R/M HNSCC treated with ICIs during August 2018 to June 2023 were included. Dynamic changes were defined as the difference between NLR and PLR on day 1 of cycles 1 and 2. RESULTS: Patients with increased NLR or PLR had an independently increased risk of disease progression at the first response evaluation (odds ratio [OR] 5.26, P = .005; OR 2.29, P = .042), disease progression (hazard ratio [HR] 2.29, P = .003; HR 1.68, P = .027), and death (HR 1.86, P = .027; HR 1.68, P = .037). Furthermore, patients with a decrease in NLR showed longer progression-free survival, with HRs of 0.36 (P < .001) for those with low pre-ICI NLR and 0.52 (P = .041) for those with high pre-ICI NLR, compared to those with increased NLR. CONCLUSIONS: Increased NLR or PLR was associated with adverse outcomes after ICI treatment in patients with R/M HNSCC.