An Efficient One-Pot Synthesis of Pyrido[2,3-c]coumarins via Serial Catalysis and Its Application in Concise Formal Synthesis of Santiagonamine.

Versatile and high-yielding one-pot synthesis of polysubstituted pyrido[2,3-c]coumarins from N-Boc-N-coumarinyl propargylamine derivatives was achieved via serial catalysis using AgSbF6. Using this approach, the concise formal synthesis of santiagonamine was successfully accomplished. This simple and versatile method could be used to increase the potential of the pyrido[2,3-c]coumarin scaffold for diverse synthetic and biological applications.

Complete genome sequence of a tentative novel capillovirus isolated from Gerbera jamesonii.

The currently named gerbera virus A (GeVA) has been shown to be a novel capillovirus with a complete genome of 6929 nucleotides (nt) (GenBank accession no. OM525829.1). GeVA was detected in Gerbera jamesonii using high-throughput RNA sequencing analysis. The GeVA genome is a single linear RNA with two open reading frames (ORF), similar to those of other capilloviruses. The larger ORF encodes a polyprotein containing four domains, while the smaller ORF encodes a movement protein. The complete genome had 41.0-54.9% nt sequence identity to other those of capilloviruses, while the polyprotein and the movement protein had 26.5-36.4% and 13.1-32.2% amino acid (aa) sequence identity, respectively. Two UUAGGU promoters for subgenomic RNA (sgRNA) transcription were also identified in this study. BLAST analysis demonstrated that the GeVA genome shared the highest sequence similarity with rubber tree capillovirus 1 (MN047299.1) (complete nucleotide sequence identity, 68.54%; polyprotein amino acid sequence identity, 44.53%). Phylogenetic analysis based on complete genome and replication protein sequences placed GeVA alongside other members of the genus Capillovirus in the family Betaflexiviridae. These data suggest that GeVA is a new member of the genus Capillovirus.

Anti-stigma training and positive changes in mental illness stigma outcomes in medical students in ten countries: a mediation analysis on pathways via empathy development and anxiety reduction.

PURPOSE: Studies of mental illness stigma reduction interventions have been criticised for failing to evaluate behavioural outcomes and mechanisms of action. This project evaluates training for medical students entitled 'Responding to Experienced and Anticipated Discrimination' (READ), developed to focus on skills in addition to attitudes and knowledge. We aimed to (i) evaluate the effectiveness of READ with respect to knowledge, attitudes, and clinical communication skills in responding to mental illness-related discrimination, and (ii) investigate whether its potential effectiveness was mediated via empathy or/and intergroup anxiety. METHODS: This is an international multisite non-randomised pre- vs post-controlled study. Eligible medical students were currently undertaking their rotational training in psychiatry. Thirteen sites across ten countries (n = 570) were included in the final analysis. RESULTS: READ was associated with positive changes in knowledge (mean difference 1.35; 95% CI 0.87 to 1.82), attitudes (mean difference - 2.50; 95% CI - 3.54 to - 1.46), skills (odds ratio 2.98; 95% CI 1.90 to 4.67), and simulated patient perceived empathy (mean difference 3.05; 95% CI 1.90 to 4.21). The associations of READ with knowledge, attitudes, and communication skills but not with simulated patient perceived empathy were partly mediated through student reported empathy and intergroup anxiety. CONCLUSION: This is the first study to identify mediating effects of reduced intergroup anxiety and increased empathy in an evaluation of anti-stigma training that includes behavioural measures in the form of communication skills and perceived empathy. It shows the importance of both mediators for all of knowledge, skills, and attitudes, and hence of targeting both in future interventions.

Drawing Guideline for JKMS Manuscripts (03): Plots for Categorical Data.

The appropriate plot effectively conveys the author's conclusions to the readers. JKMS will provide a series of special articles to show you how to make consistent and excellent plots easier. In this article, we will cover plots with categorical data. We will show what 'Bubble Plot,' 'Matrix Bubble Plot,' and 'Matrix Bar Plot' are and how to make them.

Effectiveness of Robotic Exoskeleton-Assisted Gait Training in Spinocerebellar Ataxia: A Case Report.

Spinocerebellar ataxia (SCA) is a hereditary neurodegenerative disorder that presents as ataxia. Due to the decline in balance, patients with SCA often experience restricted mobility and a decreased quality of life. Thus, many studies have emphasized the importance of physiotherapies, including gait training, in SCA patients. However, few studies have examined the effectiveness of robotic gait training in SCA. Here, we report the therapeutic outcomes of exoskeleton-assisted gait training in a patient with SCA. A 23-year-old woman with SCA participated in a gait training program using a powered lower-limb robotic exoskeleton, ANGELLEGS. The 8-week training program consisted of standing training, weight-shifting exercises, and gait training. Several measures of general function, balance, gait, and cardiopulmonary function were applied before, after, and 4 weeks after the program. After the program, overall improvements were found on scales measuring balance and gait function, and these improvements remained at 4 weeks after the program. Cardiopulmonary function was also improved 4 weeks after the program. Robotic exoskeleton gait training can be a beneficial option for training balance, gait, and cardiopulmonary function in SCA.

Clinical similarities between influenza A and B in children: a single-center study, 2017/18 season, Korea.

BACKGROUND: The global burden of seasonal influenza on medical care has been one of the greatest in the pediatric population. The attention drawn to influenza B was relatively low compared to influenza A, probably because the influenza B virus was thought to be less virulent and have a lower pandemic potential. This study aimed to compare the clinical features of influenza A and B in children. METHODS: This retrospective study included children diagnosed and treated for influenza as inpatients or outpatients during the 2017/18 influenza season at a tertiary referral hospital. Data regarding clinical characteristics, diagnoses, laboratory results, and vaccination histories were collected and reviewed. RESULTS: Over the study period, 128 patients with influenza A and 109 patients with influenza B were identified. The mean age of patients with influenza B was significantly higher than that of patients with influenza A (5.6 ± 4.4 vs 4.1 ± 4.4 years, p = 0.010). Fever was the most common manifestation of influenza followed by respiratory symptoms. No single symptom was specifically associated with either type of influenza. The total duration of fever (4.3 ± 2.3 vs 3.7 ± 2.6 days), 'time from fever onset to initiation of antivirals', and 'time from initiation of antivirals to defervescence' were similar between the two influenza types, even though all three time periods tended to be longer for influenza B. The platelet counts and proportions of neutrophils were higher for influenza A than for influenza B infections, although the values were within normal limits for both influenza types. CONCLUSIONS: We found overall clinical similarities between influenza A and B with no less clinical significance or severity of influenza B compared to those of influenza A. Equal levels of awareness and attention should be paid to both influenza types.

Measuring medication adherence in older community-dwelling patients with multimorbidity.

PURPOSE: Older people with several chronic conditions require multiple drugs from different classes to be adequately treated. This study aims to: (i) measure medication adherence across multiple conditions and therapeutic drug groups in older community-dwelling patients, and (ii) examine the effect of multimorbidity on adherence. METHODS: This is a retrospective cohort study of medication adherence in 855 community-dwelling patients aged ≥ 70 years from 15 practices in Ireland using the Health Service Executive Primary Care Reimbursement Service (HSE-PCRS) pharmacy claims database. Multimorbidity was measured using the RxRisk-V and by the number of different drug classes. The RxRisk-V algorithm classifies prescription drug fills into 45 chronic disease classes for older populations based on the WHO Anatomical Therapeutic Chemical classification system. Adherence to medications was assessed by: (i) calculating the average medication possession ratio (MPR) per patient and (ii) an MPR< 80%. RESULTS: The overall median MPR for the cohort was 0.83 (IQR 0.69, 0.91). The conditions with the highest MPRs were hypothyroidism (mean MPR = 0.88, SD = 0.20) and type 2 diabetes (mean MPR = 0.83, SD = 0.19), followed by heart disease. On average, 20-40% of patients were non-adherent (MPR < 80%) across all conditions. There was an inverted U-shaped relationship between the mean MPR and number of morbidities and drug classes. Adherence varied per patients' morbidity burden, with higher adherence for certain combinations of chronic conditions. CONCLUSION: In total, 31% of older patients with multimorbidity were non-adherent to their medication but adherence levels varied across treatment categories and chronic conditions.

Bilateral Obstructive Uropathy Caused by Congenital Bladder Diverticulum Presenting as Hypertensive Retinopathy.

A congenital bladder diverticulum (CBD) is caused by inherent muscular weakness instead of obstruction of the bladder outlet. The major clinical conditions are recurrent urinary tract infection (UTI) and voiding dysfunction. This report describes a 15-year-old male adolescent who developed sudden visual disturbance resulting from hypertensive retinopathy. The cause of hypertension was bilateral obstructive uropathy caused by enlarged paraureteral bladder diverticula. After the non-functioning right kidney and ureter and the bilateral diverticula were removed, the left ureter was reimplanted in the bladder. Pathologic findings showed chronic pyelonephritis and partial loss of the bladder musculature in the diverticular wall. This observation indicates that dilated CBD can cause latent UTI, ureteral obstruction, hydronephrosis, and secondary hypertension.

Complete nucleotide sequence and genome organization of peach virus D, a putative new member of the genus Marafivirus.

The complete nucleotide sequence of peach virus D (PeVD) from Prunus persica was determined. The PeVD genome consists of 6,612 nucleotides excluding the 3' poly(A) tail and contains a single open reading frame coding for a polyprotein of 227 kDa. Sequence comparisons and phylogenetic analysis revealed that PeVD is most closely related to viruses in the genus Marafivirus, family Tymoviridae. The complete nucleotide and CP amino acid sequences of PeVD were most similar (51.1-57.8% and 32.2-48.0%, respectively) to members of the genus Marafivirus, suggesting that PeVD is a new member of this genus.

Paricalcitol ameliorates epithelial-to-mesenchymal transition in the peritoneal mesothelium.

BACKGROUND: The purpose of the present study was to examine the effectiveness of paricalcitol for the prevention of epithelial-to-mesenchymal transition (EMT). MATERIALS AND METHODS: Human peritoneal mesothelial cells (HPMCs) were cultured in media containing transforming growth factor ß1 (TGF-ß1) with or without paricalcitol. Forty-two male Sprague-Dawley rats were divided into three groups. In the control group, the catheter was inserted but no dialysate was infused. The peritoneal dialysis (PD) group was infused with a conventional 4.25% dialysis solution. The paricalcitol group was infused with 4.25% dialysis solution and cotreated with paricalcitol. RESULTS: Exposure of HPMCs to TGF-ß1 decreased the protein level of the epithelial cell marker and increased the expression levels of the mesenchymal markers. Cotreatment with paricalcitol increased the protein levels of the epithelial cell marker and decreased those of mesenchymal markers compared with their levels in cells treated with TGF-ß1 alone. Exposure of HPMCs to TGF-ß1 significantly increased the phosphorylation of Smad2 and Smad3. Cotreatment with paricalcitol significantly decreased the phosphorylation of Smad2 and Smad3 compared with that of cells treated with TGF-ß1 alone. After 8 weeks of experimental PD in rats, the thickness of the peritoneal membrane in the PD group was significantly increased compared with that of the control group. Cotreatment with paricalcitol decreased peritoneal thickness. CONCLUSION: The present study showed that paricalcitol attenuates the TGF-ß1-induced EMT in peritoneal mesothelial cells. We suggest that paricalcitol may preserve peritoneal mesothelial cells during PD and could thus be of value for the success of long-term PD.

Protective effect of arachidonic acid and linoleic acid on 1-methyl-4-phenylpyridinium-induced toxicity in PC12 cells.

BACKGROUND: Parkinson's disease is a neurodegenerative disorder that is being characterized by the progressive loss of dopaminergic neurons of the nigrostriatal pathway in the brain. The protective effect of omega-6 fatty acids is unclear. There are lots of contradictions in the literature with regard to the cytoprotective role of arachidonic acid. To date, there is no solid evidence that shows the protective role of omega-6 fatty acids in Parkinson's disease. In the current study, the potential of two omega-6 fatty acids (i.e. arachidonic acid and linoleic acid) in alleviating 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity in PC12 cells was examined. METHODS: Cultured PC12 cells were either treated with MPP+ alone or co-treated with one of the omega-6 fatty acids for 1 day. Cell viability was then assessed by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: Cells treated with 500 µM MPP+ for a day reduced cell viability to ~70% as compared to control group. Linoleic acid (50 and 100 µM) significantly reduced MPP+-induced cell death back to ~85-90% of the control value. The protective effect could be mimicked by arachidonic acid, but not by ciglitazone. CONCLUSIONS: Both linoleic acid and arachidonic acid are able to inhibit MPP+-induced toxicity in PC12 cells. The protection is not mediated via peroxisome proliferator-activated receptor gamma (PPAR-γ). Overall, the results suggest the potential role of omega-6 fatty acids in the treatment of Parkinson's disease.

[Dietary Management of Obesity].

Obesity is defined as a condition characterized by the abnormal accumulation of fat cells, which results in increased body weight. Worldwide, obesity is progressively on the rise, leading to an increased prevalence of chronic conditions such as cardiovascular disease, type 2 diabetes, and hyperlipidemia. Obesity is a result of the interplay between genetic, metabolic, social, behavioral, and cultural factors, necessitating an interdisciplinary and multimodal management approach. Diet therapy, which includes dietary modifications and nutritional interventions, is a fundamental component of the multifaceted approach to managing obesity. The principle of diet therapy is based on achieving weight loss through a negative energy balance and maintaining weight through an equilibrium of energy intake and expenditure. Strategies for weight loss and control rely on caloric restriction, macronutrient distribution, and dietary patterns such as the Mediterranean and Dietary Approaches to Stop Hypertension (DASH) diets. Recently, studies have been conducted on weight control using information and communication technology-based interventions, as well as interventions based on intestinal microorganisms which consider inter-individual variability and long-term adherence. In conclusion, diet therapy stands as a pivotal element in the management of obesity, providing a personalized and comprehensive approach to weight control. By combining evidence-based dietary strategies with behavioral modifications and consistent support, healthcare professionals can enable individuals to attain and sustain a healthier weight, thereby reducing related health risks.

Does Spinal Cord-Canal Mismatch Adversely Affect the Clinical Outcomes of Anterior Cervical Discectomy and Fusion for the Treatment of Cervical Myelopathy?

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To clarify whether clinical outcomes of anterior cervical discectomy and fusion (ACDF), is affected by presence of spinal canal-cord mismatch (SCCM). SUMMARY OF BACKGROUND DATA: SCCM is considered a factor that would moderately influence surgeons to perform posterior surgery since it could widen the spinal canal, while an anterior approach could only remove degenerative pathologies grown into the spinal canal. METHODS: We retrospectively reviewed 186 patients who underwent ACDF and had been followed-up for >2 years. Patients with spinal cord occupation ratio (SCOR) of ≥0.7 were classified into the SCCM group, while those with a SCOR of <0.7 were included in the no-SCCM group. Patient demographics, cervical sagittal parameters, neck pain visual analog scale (VAS), arm pain VAS, and Japanese Orthopedic Association (JOA) score were assessed. JOA score was the primary outcome of the study. RESULTS: One-hundred and forty-seven patients (79.0%) were included into the no-SCCM group, while 39 patients (21.0%) were classified into the SCCM group. Postoperative radiographic parameters including C2-C7 lordosis, C2-C7 sagittal vertical axis, and range of motion did not significantly differ between the two groups. Neck pain VAS, arm pain VAS, and JOA score (no-SCCM group, from 13.7±2.5 to 14.6±2.3, P<0.001; SCCM group, from 13.8±1.6 to 15.0±2.0, P<0.001) significantly improved after the operation in both groups, and results were not significantly different between the two groups. Furthermore, SCOR was not significantly associated with JOA recovery rate at 2 years postoperatively in linear regression analysis. CONCLUSION: Clinical and radiographic outcomes of ACDF were not affected by the presence of SCCM. Furthermore, SCOR was not significantly associated with neurologic recovery at 2 years of follow-up. Therefore, ACDF can be safely and effectively applied for treating cervical myelopathy, regardless of the presence of SCCM, when other factors favor the anterior approach. LEVEL OF EVIDENCE: 3.

Paraquat and Parkinson's Disease: The Molecular Crosstalk of Upstream Signal Transduction Pathways Leading to Apoptosis.

Parkinson's disease (PD) is a heterogeneous disease involving a complex interaction between genes and the environment that affects various cellular pathways and neural networks. Several studies have suggested that environmental factors such as exposure to herbicides, pesticides, heavy metals, and other organic pollutants are significant risk factors for the development of PD. Among the herbicides, paraquat has been commonly used, although it has been banned in many countries due to its acute toxicity. Although the direct causational relationship between paraquat exposure and PD has not been established, paraquat has been demonstrated to cause the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The underlying mechanisms of the dopaminergic lesion are primarily driven by the generation of reactive oxygen species, decrease in antioxidant enzyme levels, neuroinflammation, mitochondrial dysfunction, and ER stress, leading to a cascade of molecular crosstalks that result in the initiation of apoptosis. This review critically analyses the crucial upstream molecular pathways of the apoptotic cascade involved in paraquat neurotoxicity, including mitogenactivated protein kinase (MAPK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT, mammalian target of rapamycin (mTOR), and Wnt/ß-catenin signaling pathways.

Time division multiplexing based multi-spectral semantic camera for LiDAR applications.

The recent progress in the development of measurement systems for autonomous recognition had a substantial impact on emerging technology in numerous fields, especially robotics and automotive applications. In particular, time-of-flight (TOF) based light detection and ranging (LiDAR) systems enable to map the surrounding environmental information over long distances and with high accuracy. The combination of advanced LiDAR with an artificial intelligence platform allows enhanced object recognition and classification, which however still suffers from limitations of inaccuracy and misidentification. Recently, multi-spectral LiDAR systems have been employed to increase the object recognition performance by additionally providing material information in the short-wave infrared (SWIR) range where the reflection spectrum characteristics are typically very sensitive to material properties. However, previous multi-spectral LiDAR systems utilized band-pass filters or complex dispersive optical systems and even required multiple photodetectors, adding complexity and cost. In this work, we propose a time-division-multiplexing (TDM) based multi-spectral LiDAR system for semantic object inference by the simultaneous acquisition of spatial and spectral information. By utilizing the TDM method, we enable the simultaneous acquisition of spatial and spectral information as well as a TOF based distance map with minimized optical loss using only a single photodetector. Our LiDAR system utilizes nanosecond pulses of five different wavelengths in the SWIR range to acquire sufficient material information in addition to 3D spatial information. To demonstrate the recognition performance, we map the multi-spectral image from a human hand, a mannequin hand, a fabric gloved hand, a nitrile gloved hand, and a printed human hand onto an RGB-color encoded image, which clearly visualizes spectral differences as RGB color depending on the material while having a similar shape. Additionally, the classification performance of the multi-spectral image is demonstrated with a convolution neural network (CNN) model using the full multi-spectral data set. Our work presents a compact novel spectroscopic LiDAR system, which provides increased recognition performance and thus a great potential to improve safety and reliability in autonomous driving.

Hybrid nutraceutical of 2-ketoglutaric acid in improving inflammatory bowel disease: Role of prebiotics and TAK1 inhibitor.

The main cause of inflammatory bowel disease (IBD) is abnormal intestinal permeability due to the disruption of the tight junction of the intestinal barrier through a pathogen-mediated inflammatory mechanism and an imbalance of the gut microbiota. This study aimed to evaluate whether 2-ketoglutaric acid alleviated permeability dysfunction with tight junction localization, activated the transforming growth factor beta-activated kinase 1 (TAK1) inflammation pathway, and regulated the homeostasis of the intestinal microbiome in vitro and in vivo IBD model. Our findings revealed that 2-ketoglutaric acid significantly suppressed abnormal intestinal permeability, delocalization of tight junction proteins from the intestinal cell, expression of inflammatory cytokines, such as TNF-α, both in vitro and in vivo. 2-Ketoglutaric acid was found to directly bind to TAK1 and inhibit the TNF receptor-associated factor 6 (TRAF6)-TAK1 interaction, which is related to the activation of nuclear factor kappa B (NF-κB) pathways, thereby regulating the expression of mitogen-activated protein kinase. Dietary 2-ketoglutaric acid also alleviated gut microbiota dysbiosis and IBD symptoms, as demonstrated by improvements in the intestine length and the abundance of Ligilactobacillus, Coriobacteriaceae_UCG_002, and Ruminococcaceae_unclassified in mice with colitis. This study indicated that 2-ketoglutaric acid binds to TAK1 for activity inhibition which is related to the NF-κB pathway and alleviates abnormal permeability by regulating tight junction localization and gut microbiome homeostasis. Therefore, 2-ketoglutaric acid is an effective nutraceutical agent and prebiotic for the treatment of IBD.

Multichannel Hierarchical Analysis of Time-Resolved Hyperspectral Data for Advanced Colorimetric E-Nose.

The colorimetric sensor-based electronic nose has been demonstrated to discriminate specific gaseous molecules for various applications, including health or environmental monitoring. However, conventional colorimetric sensor systems rely on RGB sensors, which cannot capture the complete spectral response of the system. This limitation can degrade the performance of machine learning analysis, leading to inaccurate identification of chemicals with similar functional groups. Here, we propose a novel time-resolved hyperspectral (TRH) data set from colorimetric array sensors consisting of 1D spatial, 1D spectral, and 1D temporal axes, which enables hierarchical analysis of multichannel 2D spectrograms via a convolution neural network (CNN). We assessed the outstanding classification performance of the TRH data set compared to an RGB data set by conducting a relative humidity (RH) concentration classification. The time-dependent spectral response of the colorimetric sensor was measured and trained as a CNN model using TRH and RGB sensor systems at different RH levels. While the TRH model shows a high classification accuracy of 97.5% for the RH concentration, the RGB model yields 72.5% under identical conditions. Furthermore, we demonstrated the detection of various functional volatile gases with the TRH system by using experimental and simulation approaches. The results reveal distinct spectral features from the TRH system, corresponding to changes in the concentration of each substance.

Impact of vehicles at the roadside of expressway in urban area: Simultaneous measurement of particle size distribution and positive matrix factorization.

This study conducted real-time monitoring of size-resolved particle concentrations ranging from 9 nm to 10 µm simultaneously at four sites on the park ground and the roof of a five-story apartment buildings in the upwind and downwind areas of the Olympic Expressway next to apartment complex areas of Seoul, Korea. Using a positive matrix factorization model for source apportionment, eight factors were resolved at each monitoring site: four exhaust emissions of vehicles, one non-exhaust emission of vehicle, two regional sources, and one unknown source. After categorizing monitoring data into three cases by wind conditions, impact and contribution of each vehicle-related source on the local road to the roadside pollution was quantified and characterized by subtracting the urban background concentrations. Throughout the measurement period, the contribution of vehicle-related sources to the particle number concentration at each monitoring site ranged from 61 % to 69 %, while that to the particle mass concentration ranged from 39 % to 87 %. During periods of steady traffic flow and wind blowing from the road to three downwind sites at speeds exceeding >0.5 m/s during working hours, the particle number concentrations at the downwind sites were 2.2-2.5 times higher than the average levels. Among vehicle-related sources, gasoline vehicles with multiple injections or high-emitting diesel vehicles showed the highest contribution to particle number concentrations at all sites. As wind speed increased, the number concentrations of particles from vehicle exhaust and non-exhaust emissions decreased and increased, respectively, probably due to enhanced dilution and transport, respectively. In addition, particle number concentrations showed a parabolic curve-like trend with traffic volumes increasing to approximately 10,000 vehicles/h, and then decreasing for both vehicle exhaust and non-exhaust emissions. These results can be utilized in numerical modeling studies and in establishing traffic-related environmental policies to reduce seasonal and temporal particle exposure near the roadsides.

Health-related quality of life after 12 months post discharge in patients hospitalised with COVID-19-related severe acute respiratory infection (SARI): a prospective analysis of SF-36 data and correlation with retrospective admission data on age, disease severity, and frailty.

Long-term outcome and 'health-related quality of life' (HRQoL) following hospitalisation for COVID-19-related severe acute respiratory infection (SARI) is limited. OBJECTIVE: To assess the impact of HRQoL in patients hospitalised with COVID-19-related SARI at 1 year post discharge, focusing on the potential impact of age, frailty, and disease severity. METHOD: Routinely collected outcome data on 1207 patients admitted with confirmed COVID-19 related SARI across all three secondary care sites in our NHS trust over 3 months were assessed in this retrospective cohort study. Of those surviving 1 year, we prospectively collected 36-item short form (SF-36) HRQoL questionnaires, comparing three age groups (<49, 49-69, and the over 69-year-olds), the relative impact of frailty (using the Clinical Frailty Score; CFS), and disease severity (using National Early Warning Score; NEWS) on HRQoL domains. RESULTS: Overall mortality was 46.5% in admitted patients. In our SF-36 cohort (n=169), there was a significant reduction in all HRQoL domains versus normative data; the most significant reductions were in the physical component (p<0.001) across all ages and the emotional component (p<0.01) in the 49-69 year age group, with age having no additional impact on HRQoL. However, there was a significant correlation between physical well-being versus CFS (the correlation coefficient=-0.37, p<0.05), though not NEWS, with no gender difference observed. CONCLUSION: There was a significant reduction in all SF-36 domains at 1 year. Poor CFS at admission was associated with a significant and prolonged impact on physical parameters at 1 year. Age had little impact on the severity of HRQoL, except in the domains of physical functioning and the overall physical component.

Innate Immune-Enhancing Effect of Pinus densiflora Pollen Extract via NF-κB Pathway Activation.

Considering the emergence of various infectious diseases, including the coronavirus disease 2019 (COVID-19), people's attention has shifted towards immune health. Consequently, immune-enhancing functional foods have been increasingly consumed. Hence, developing new immune-enhancing functional food products is needed. Pinus densiflora pollen can be collected from the male red pine tree, which is commonly found in Korea. P. densiflora pollen extract (PDE), obtained by water extraction, contained polyphenols (216.29 ± 0.22 mg GAE/100 g) and flavonoids (35.14 ± 0.04 mg CE/100 g). PDE significantly increased the production of nitric oxide (NO) and reactive oxygen species (ROS) but, did not exhibit cytotoxicity in RAW 264.7 cells. Western blot results indicated that PDE induced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. PDE also significantly increased the mRNA and protein levels of cytokines and the phosphorylation of IKKα/ß and p65, as well as the activation and degradation of IκBα. Additionally, western blot analysis of cytosolic and nuclear fractions and immunofluorescence assay confirmed that the translocation of p65 to the nucleus after PDE treatment. These results confirmed that PDE increases the production of cytokines, NO, and ROS by activating NF-κB. Therefore, PDE is a promising nutraceutical candidate for immune-enhancing functional foods.