Chronic allergic asthma induces T-cell exhaustion and impairs virus clearance in mice.

BACKGROUND: Allergic asthma, one of the most common types of asthma, is thought to be highly susceptible to respiratory viral infections; however, its pathological mechanism needs to be elucidated. Recent studies have found impaired T-cell function in asthmatic mice. Therefore, we aimed to investigate the way by which asthma induction affects T-cell exhaustion in the lungs and assess the relationship between T-cell exhaustion and influenza viral infection. METHODS: Chronic allergic asthma mice were induced by intranasal injection of ovalbumin for 6 weeks and asthmatic features and T cell populations in lung or airway were assessed. To determine the influenza virus susceptibility, control and asthma mice were challenged with the human influenza virus strain A/Puerto Rico/8/1934 H1N1 and evaluated the survival rate, lung damage, and virus titer. RESULTS: Six weeks of OVA sensitization and challenge successfully induced chronic allergic asthma in a mouse model showing significant increase of sera IgE level and broncho-pathological features. A significant decrease in interferon-γ-producing T-cell populations and an increase in exhausted T-cell populations in the lungs of OVA-induced asthmatic mice were observed. Asthmatic mice were more susceptible to influenza virus infection than control mice showing lower survival rate and higher virus titer in lung, and a positive correlation existed between T-cell exhaustion in the lung and virus titer. CONCLUSIONS: Asthma induction in mice results in the exhaustion of T-cell immunity, which may contribute to the defective capacity of viral protection. This study demonstrates a correlation between asthma conditions and viral susceptibility by investigating the functional characteristics of T-cells in asthma. Our results provide insights into the development of strategies to overcome the dangers of respiratory viral disease in patients with asthma.

Comparative study of lumbar bone mineral content using DXA and CT Hounsfield unit values in chest CT.

BACKGROUND: Bone mineral content (BMC) values in certain bones and changes in BMC over time are key features for diagnosing osteoporosis. This study examined those features using morphometric texture analysis in chest computational tomography (CT) by comparing a dual-energy X-ray absorptiometry (DXA)-based BMC. An accessible approach for screening osteoporosis was suggested by accessing BMC using only Hounsfield units (HU). METHODOLOGY: The study included a total of 510 cases (255 patients) acquired between May 6, 2012, and June 30, 2020, at a single institution. Two cases were associated with two chest CT scans from one patient with a scan interval of over two years, and each scan was followed soon after by a DXA scan. Axial cuts of the first lumbar vertebra in CT and DXA-based L1 BMC values were corrected for each case. The maximum trabecular area was selected from the L1 spine body, and 45 texture features were extracted from the region using gray-level co-occurrence matrices. A regression model was employed to estimate the absolute BMC value in each case using 45 features. Also, an additional regression model was used to estimate the change in BMC between two scans for each patient using 90 features from the corresponding cases. RESULTS: The correlation coefficient (CC) and mean absolute error (MAE) between estimates and DXA references were obtained for the evaluation of regressors. In the case of the BMC estimation, CC and MAE were 0.754 and 1.641 (g). In the case of the estimation of change in BMC, CC and MAE were 0.680 and 0.528 (g). CONCLUSION: The modality using morphometric texture analysis with CT HUs can indirectly help screening osteoporosis because it provides estimates of BMC and BMC change that show moderate positive correlations with DXA measures.

Effectiveness of ultrasound-guided dual nerve block in the below-knee amputation.

PURPOSE: Below knee amputation (BKA) is a common surgical procedure for diabetic foot ulcers and necrotizing lower limb fasciitis patients. However, it is a painful procedure and inadequate postoperative analgesia impedes rehabilitation and prolongs hospitalization. An ideal pain management regimen should provide superior analgesia while minimizing opioid consumption and improving rehabilitation. METHODS: We retrospectively reviewed medical charts of 218 patients who underwent BKA for diabetic foot ulcer or necrotizing lower limb fasciitis at a single center between January 2017 and September 2020. Two groups were analyzed: patients who received dual nerve block (DNB) before surgery (Group I; n = 104), and patients who did not (Group II; n = 93). By the exclusion criteria, 21 patients were excluded. The femoral and sciatic nerves were each blocked separately under ultrasound guidance. This procedure was performed immediately before the operation. RESULTS: Group I patients' subjective pain scores were significantly lower than that of Group II at 6, 12, and 24 h after BKA (P < 0.05). Group I's morphine milligram equivalent (MME) was significantly lower than those of Group II at 72 h after BKA (P < 0.05). Moreover, the rate of postoperative nausea and vomiting (PONV) and delirium was significantly lower in Group I patients than that in Group II patients. CONCLUSION: Ultrasound-guided lower extremity nerve block surgery is excellent for early postoperative pain control, could be used as an accurate and effective pain control method, and can reduce the side effects of opioid consumption after BKA.

The impact of obesity on the accuracy of DXA BMD for DXA-equivalent BMD estimation.

INTRODUCTION: As the radiomics technique using texture features in CT is adopted for accessing DXA-equivalent bone mineral density (BMD), this study aims to compare BMD by DXA and predicted BMD to investigate the impact of obesity and central obesity in general patients. MATERIALS AND METHODS: A total of 710 cases (621 patients) obtained from May 6, 2012, to June 30, 2021, were used in the study. We focused both their abdomen & pelvis CT's first lumbar vertebrae axial cuts to predict estimated BMD and bone mineral content (BMC). In each patient's CT, we extracted the largest trabecular region of the L1 vertebral body as a region of interest (ROI) using the gray-level co-occurrence matrices (GLCM) technique, and linear regression was applied to predict the indices. Cases were divided by central obesity/overall obesity and normal group by body mass index (BMI), waist circumference (WC), or index of central obesity (ICO) standard. RESULTS: The coefficients were all above 0.73, respectively. P-values from ICO were over 0.05 when the measures were Hip BMD and Hip BMC. In contrast, those from ICO were 0.0131 and 0.0351 when the measures were L1 BMD and L1 BMC, respectively, which show a difference between the two groups. CONCLUSIONS: The CT HU texture analysis method was an effective and economical method for measuring estimated BMD and BMC and evaluating the impact of obesity. We found that central obesity especially exerted an effect on the disturbance of the clinical BMD measurements since groups were significantly different under the ICO standard.

Anti-Thrombotic Effects of Artesunate through Regulation of cAMP and PI3K/MAPK Pathway on Human Platelets.

Normal activation of platelets and their aggregation are crucial for proper hemostasis. It appears that excessive or abnormal aggregation of platelets may bring about cardiovascular diseases such as stroke, atherosclerosis, and thrombosis. For this reason, finding a substance that can regulate platelet aggregation or suppress aggregation will aid in the prevention and treatment of cardiovascular diseases. Artesunate is a compound extracted from the plant roots of Artemisia or Scopolia, and its effects have shown to be promising in areas of anticancer and Alzheimer's disease. However, the role and mechanisms by which artesunate affects the aggregation of platelets and the formation of a thrombus are currently not understood. This study examines the ways artesunate affects the aggregation of platelets and the formation of a thrombus on platelets induced by U46619. As a result, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) production were increased significantly by artesunate relative to the doses, as well as phosphorylated vasodilator-stimulated phosphoprotein (VASP) and inositol 1,4,5-trisphosphate receptor (IP3R), substrates to cAMP-dependent kinase and cGMP-dependent kinase, in a significant manner. The Ca2+, normally mobilized from the dense tubular system, was inhibited due to IP3R phosphorylation from artesunate, and phosphorylated VASP aided in inhibiting platelet activity via αIIb/ß3 platelet membrane inactivation and inhibiting fibrinogen binding. In addition, MAPK and PI3K/Akt phosphorylation was inhibited via artesunate in a significant manner, causing the production of TXA2 and intracellular granular secretion (serotonin and ATP release) to be reduced. Therefore, we suggest that artesunate has value as a substance that inhibits platelet aggregation and thrombus formation through an antiplatelet mechanism.

Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi in foals.

Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatography. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC24h/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 µg/mL at 1.52 h (Tmax) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 µg/mL. The ex vivo AUC24h/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC24h/MIC values and pharmacokinetic parameters, cefquinome when administered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused by S. equi in foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment.

Identification of the Female-Produced Sex Pheromone of the Dotted White Geometrid Naxa seriaria (Lepidoptera: Geometridae).

The dotted white geometrid moth, Naxa seriaria Motschulsky (Lepidoptera: Geometridae), is a pest of Oleaceae in Korea, Japan, and China. In this study, we identified (3Z,6Z,9Z,12Z,15Z)-heneicosapentaene (C-21 pentaene) as the only compound in extracts of the pheromone glands of female N. seriaria causing a response from receptors on the antennae of males in analyses by gas chromatography with electroantennographic detection. The synthetic sex pheromone elicited dose-dependent electrophysiological responses from antennae of male N. seriaria. In field tests, more male moths were captured in traps baited with synthetic C-21 pentaene than in unbaited traps, and increasing the loading of C-21 pentaene in the lure increased catches of male moths. Significantly more male N. seriaria moths were caught in delta traps than in bucket traps. Based on these results, C-21 pentaene is proposed to be the major, if not the only, component of the sex pheromone of N. seriaria.

Gintonin modulates platelet function and inhibits thrombus formation via impaired glycoprotein VI signaling.

Panax ginseng (P. ginseng), one of the most valuable medicinal plants, is known for its healing and immunobooster properties and has been widely used in folk medicine against cardiovascular diseases, including stroke and heart attack. In this study, we explored the anti-platelet activity of gintonin (a recently discovered non-saponin fraction of ginseng) against agonist-induced platelet activation. In vitro effects of gintonin on agonist-induced human and rat platelet aggregation, granule secretion, integrin αIIbß3 activation, and intracellular calcium ion ([Ca2+]i) mobilization were examined. Western blot analysis and immunoprecipitation techniques were used to estimate the expression of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and interaction of glycoprotein VI (GPVI) signaling pathway molecules such as Src family kinases (SFK), tyrosine kinase Syk, and PLCγ2. In vivo effects were studied using acute pulmonary thromboembolism model in mice. Gintonin remarkably inhibited collagen-induced platelet aggregation and suppressed granule secretion, [Ca2+]i mobilization, and fibrinogen binding to integrin αIIbß3 in a dose-dependent manner and clot retraction. Gintonin attenuated the activation of MAPK molecules and PI3K/Akt pathway. It also inhibited SFK, Syk, and PLCγ2 activation and protected mice from thrombosis. Gintonin inhibited agonist-induced platelet activation and thrombus formation through impairment in GPVI signaling molecules, including activation of SFK, Syk, PLCγ2, MAPK, and PI3K/Akt; suggesting its therapeutic potential against platelet related CVD.

Evaluation of Machine Learning Algorithms for Surface Water Extraction in a Landsat 8 Scene of Nepal.

With over 6000 rivers and 5358 lakes, surface water is one of the most important resources in Nepal. However, the quantity and quality of Nepal's rivers and lakes are decreasing due to human activities and climate change. Despite the advancement of remote sensing technology and the availability of open access data and tools, the monitoring and surface water extraction works has not been carried out in Nepal. Single or multiple water index methods have been applied in the extraction of surface water with satisfactory results. Extending our previous study, the authors evaluated six different machine learning algorithms: Naive Bayes (NB), recursive partitioning and regression trees (RPART), neural networks (NNET), support vector machines (SVM), random forest (RF), and gradient boosted machines (GBM) to extract surface water in Nepal. With three secondary bands, slope, NDVI and NDWI, the algorithms were evaluated for performance with the addition of extra information. As a result, all the applied machine learning algorithms, except NB and RPART, showed good performance. RF showed overall accuracy (OA) and kappa coefficient (Kappa) of 1 for the all the multiband data with the reference dataset, followed by GBM, NNET, and SVM in metrics. The performances were better in the hilly regions and flat lands, but not well in the Himalayas with ice, snow and shadows, and the addition of slope and NDWI showed improvement in the results. Adding single secondary bands is better than adding multiple in most algorithms except NNET. From current and previous studies, it is recommended to separate any study area with and without snow or low and high elevation, then apply machine learning algorithms in original Landsat data or with the addition of slopes or NDWI for better performance.

Evaluation of Water Indices for Surface Water Extraction in a Landsat 8 Scene of Nepal.

Accurate and frequent updates of surface water have been made possible by remote sensing technology. Index methods are mostly used for surface water estimation which separates the water from the background based on a threshold value. Generally, the threshold is a fixed value, but can be challenging in the case of environmental noise, such as shadow, forest, built-up areas, snow, and clouds. One such challenging scene can be found in Nepal where no such evaluation has been done. Taking that in consideration, this study evaluates the performance of the most widely used water indices: Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), Modified NDWI (MNDWI), and Automated Water Extraction Index (AWEI) in a Landsat 8 scene of Nepal. The scene, ranging from 60 m to 8848 m, contains various types of water bodies found in Nepal with different forms of environmental noise. The evaluation was conducted based on measures from a confusion matrix derived using validation points. Comparing visually and quantitatively, not a single method was able to extract surface water in the entire scene with better accuracy. Upon selecting optimum thresholds, the overall accuracy (OA) and kappa coefficient (kappa) was improved, but not satisfactory. NDVI and NDWI showed better results for only pure water pixels, whereas MNDWI and AWEI were unable to reject snow cover and shadows. Combining NDVI with NDWI and AWEI with shadow improved the accuracy but inherited the NDWI and AWEI characteristics. Segmenting the test scene with elevations above and below 665 m, and using NDVI and NDWI for detecting water, resulted in an OA of 0.9638 and kappa of 0.8979. The accuracy can be further improved with a smaller interval of categorical characteristics in one or multiple scenes.

Identification of the Aggregation-sex Pheromone Produced by Male Monochamus saltuarius, a Major Insect Vector of the Pine Wood Nematode.

In this study, we isolated and identified an aggregation-sex pheromone from Monochamus saltuarius, the major insect vector of the pine wood nematode in Korea. Adult males of M. saltuarius produce 2-undecyloxy-1-ethanol, which is known as an aggregation-sex pheromone in other Monochamus species. We performed field experiments to determine the attractiveness of the pheromone and other synergists. More M. saltuarius adult beetles were attracted to traps baited with the pheromone than to unbaited traps. Ethanol and (-)-α-pinene interacted synergistically with the pheromone. Traps baited with the pheromone + (-)-α-pinene +ethanol were more attractive to M. saltuarius adults than traps baited with the pheromone, (-)-α-pinene, or ethanol alone. Ipsenol, ipsdienol, and limonene were also identified as synergists of the aggregation-sex pheromone for M. saltuarius adults. In field experiments, the proportion of females was much higher in the beetles caught in traps than among the beetles emerging from naturally-infested logs in the laboratory. Our results suggest that a combination of aggregation-sex pheromone and synergists could be very effective for monitoring and managing M. saltuarius.

Identification of Water Bodies in a Landsat 8 OLI Image Using a J48 Decision Tree.

Water bodies are essential to humans and other forms of life. Identification of water bodies can be useful in various ways, including estimation of water availability, demarcation of flooded regions, change detection, and so on. In past decades, Landsat satellite sensors have been used for land use classification and water body identification. Due to the introduction of a New Operational Land Imager (OLI) sensor on Landsat 8 with a high spectral resolution and improved signal-to-noise ratio, the quality of imagery sensed by Landsat 8 has improved, enabling better characterization of land cover and increased data size. Therefore, it is necessary to explore the most appropriate and practical water identification methods that take advantage of the improved image quality and use the fewest inputs based on the original OLI bands. The objective of the study is to explore the potential of a J48 decision tree (JDT) in identifying water bodies using reflectance bands from Landsat 8 OLI imagery. J48 is an open-source decision tree. The test site for the study is in the Northern Han River Basin, which is located in Gangwon province, Korea. Training data with individual bands were used to develop the JDT model and later applied to the whole study area. The performance of the model was statistically analysed using the kappa statistic and area under the curve (AUC). The results were compared with five other known water identification methods using a confusion matrix and related statistics. Almost all the methods showed high accuracy, and the JDT was successfully applied to the OLI image using only four bands, where the new additional deep blue band of OLI was found to have the third highest information gain. Thus, the JDT can be a good method for water body identification based on images with improved resolution and increased size.

Advancements in Skin-Mediated Drug Delivery: Mechanisms, Techniques, and Applications.

Skin-mediated drug delivery methods currently are receiving significant attention as a promising approach for the enhanced delivery of drugs through the skin. Skin-mediated drug delivery offers the potential to overcome the limitations of traditional drug delivery methods, including oral administration and intravenous injection. The challenges associated with drug permeation through layers of skin, which act as a major barrier, are explored, and strategies to overcome these limitations are discussed in detail. This review categorizes skin-mediated drug delivery methods based on the means of increasing drug permeation, and it provides a comprehensive overview of the mechanisms and techniques associated with these methods. In addition, recent advancements in the application of skin-mediated drug delivery are presented. The review also outlines the limitations of ongoing research and suggests future perspectives of studies regarding the skin-mediated delivery of drugs.

Retrospective Analysis of Ultrasound-Guided Serial-Injection Triple Nerve Block Efficacy in Cementless Bipolar Hemiarthroplasty for Femoral Neck Fracture.

BACKGROUND: Femoral neck fractures are effectively treated with bipolar hemiarthroplasty (BHA) surgery, yet postoperative pain management remains a challenge. This study explores the efficacy of multimodal pain management in minimizing opioid use and enhancing recovery. METHODS: A retrospective analysis of 87 patients who underwent BHA between September 2016 and September 2020 was conducted. Patients were analyzed in two groups: Group I (n = 42), receiving serial-injection nerve blocks (SINBs) before and after surgery, and Group II (n = 41), with no SINB. Notably, all nerve blocks for Group I were performed after November 2017, following the implementation of this technique in our protocol. Pain and analgesic medication usage were assessed over 72 h post-surgery, along with hospitalization duration and perioperative complications. RESULTS: Group I patients exhibited significantly lower pain scores at 6, 12, 24, and 48 h post-surgery, alongside reduced incidences of postoperative nausea and vomiting (PONV) and delirium compared with Group II (p < 0.05). CONCLUSIONS: Utilizing sequential lower limb nerve blocks under ultrasound guidance in BHA surgeries effectively reduces early postoperative pain and associated adverse effects. This approach demonstrates potential benefits in pain management, leading to diminished narcotic usage and lower risks of PONV and delirium.

Discordance between dual-energy X-ray absorptiometry bone mineral density and spinal computed tomography texture analysis: An investigation into low correlation rates.

Objectives: This research delves into the application of texture analysis in spine computed tomography (CT) scans and its correlation with bone mineral density (BMD), as determined by dual-energy X-ray absorptiometry (DXA). It specifically addresses the discordance between the 2 measurements, suggesting that certain spinal-specific factors may contribute to this discrepancy. Methods: The study involved 405 cases from a single institution collected between May 6, 2012 and June 30, 2021. Each case underwent a spinal CT scan and a DXA scan. BMD values at the lumbar region (T12 to S1) and total hip were recorded. Texture features from axial cuts of T12 to S1 vertebrae were extracted using gray-level co-occurrence matrices, and a regression model was constructed to predict the BMD values. Results: The correlation between CT texture analysis results and BMD from DXA was moderate, with a correlation coefficient ranging between 0.4 and 0.5. This discordance was examined in light of factors unique to the spine region, such as abdominal obesity, aortic calcification, and lumbar degenerative changes, which could potentially affect BMD measurements. Conclusions: Emerging from this study is a novel insight into the discordance between spinal CT texture analysis and DXA-derived BMD measurements, highlighting the unique influence of spinal attributes. This revelation calls into question the exclusive reliance on DXA scans for BMD assessment, particularly in scenarios where DXA scanning may not be feasible or accurate.

Monophosphoryl lipid A and poly I:C combination enhances immune responses of equine influenza virus vaccine.

Equine influenza is a contagious respiratory disease caused by H3N8 type A influenza virus. Vaccination against equine influenza is conducted regularly; however, infection still occurs globally because of the short immunity duration and suboptimal efficacy of current vaccines. Hence the objective of this study was to investigate whether an adjuvant combination can improve immune responses to equine influenza virus (EIV) vaccines. Seventy-two mice were immunized with an EIV vaccine only or with monophosphoryl lipid A (MPL), polyinosinic-polycytidylic acid (Poly I:C), or MPL + Poly I:C. Prime immunization was followed by boost immunization after 2 weeks. Mice were euthanized at 4, 8, and 32 weeks post-prime immunization, respectively. Sera were collected to determine humoral response. Bone marrow, spleen, and lung samples were harvested to determine memory cell responses, antigen-specific T-cell proliferation, and lung viral titers. MPL + Poly I:C resulted in the highest IgG, IgG1, and IgG2a antibodies and hemagglutination inhibition titers among the groups and sustained their levels until 32 weeks post-prime immunization. The combination enhanced memory B cell responses in the bone marrow and spleen. At 8 weeks post-prime immunization, the combination induced higher CD8+ central memory T cell frequencies in the lungs and CD8+ central memory T cells in the spleen. In addition, the combination group exhibited enhanced antigen-specific T cell proliferation, except for CD4+ T cells in the lungs. Our results demonstrated improved immune responses when using MPL + Poly I:C in EIV vaccines by inducing enhanced humoral responses, memory cell responses, and antigen-specific T cell proliferation.

Power-integrated, wireless neural recording systems on the cranium using a direct printing method for deep-brain analysis.

Conventional power-integrated wireless neural recording devices suffer from bulky, rigid batteries in head-mounted configurations, hindering the precise interpretation of the subject's natural behaviors. These power sources also pose risks of material leakage and overheating. We present the direct printing of a power-integrated wireless neural recording system that seamlessly conforms to the cranium. A quasi-solid-state Zn-ion microbattery was 3D-printed as a built-in power source geometrically synchronized to the shape of a mouse skull. Soft deep-brain neural probes, interconnections, and auxiliary electronics were also printed using liquid metals on the cranium with high resolutions. In vivo studies using mice demonstrated the reliability and biocompatibility of this wireless neural recording system, enabling the monitoring of neural activities across extensive brain regions without notable heat generation. This all-printed neural interface system revolutionizes brain research, providing bio-conformable, customizable configurations for improved data quality and naturalistic experimentation.

In-vivo integration of soft neural probes through high-resolution printing of liquid electronics on the cranium.

Current soft neural probes are still operated by bulky, rigid electronics mounted to a body, which deteriorate the integrity of the device to biological systems and restrict the free behavior of a subject. We report a soft, conformable neural interface system that can monitor the single-unit activities of neurons with long-term stability. The system implements soft neural probes in the brain, and their subsidiary electronics which are directly printed on the cranial surface. The high-resolution printing of liquid metals forms soft neural probes with a cellular-scale diameter and adaptable lengths. Also, the printing of liquid metal-based circuits and interconnections along the curvature of the cranium enables the conformal integration of electronics to the body, and the cranial circuit delivers neural signals to a smartphone wirelessly. In the in-vivo studies using mice, the system demonstrates long-term recording (33 weeks) of neural activities in arbitrary brain regions. In T-maze behavioral tests, the system shows the behavior-induced activation of neurons in multiple brain regions.

In vitro effects of monophosphoryl lipid A and Poly I:C combination on equine cells.

BACKGROUND: Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. OBJECTIVES: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). METHODS: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination. The mRNA expression of interferon gamma (IFN-γ), interleukin (IL)-1ß, IL-4, IL-6, IL-8, IL-12p40, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1) was determined using real-time polymerase chain reaction. RESULTS: The combination of MPL and Poly I:C significantly upregulated immunomodulatory responses in equine cells/ without cytotoxicity. The combination induced greater mRNA expression of pro-inflammatory cytokines IFN-γ and IL-6 than MPL or Poly I:C stimulation alone in PBMCs. In addition, the combination induced significantly higher mRNA expression of IL-1ß, IL-6, and IL-12p40 in MoDCs, and IL-8, MCP-1, and VEGF in BM-MSCs compared to stimulation with a single TLR agonist. CONCLUSIONS: The combination of MPL and Poly I:C can be used as a potential adjuvant candidate for vaccines to aid in preventing infectious diseases in horses.

Risk Factors of the 2-Year Mortality after Bipolar Hemiarthroplasty for Displaced Femoral Neck Fracture.

Purpose: This study investigates the relationship between preoperative neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCR), albumin, and 2-year mortality in elderly patients having hemiarthroplasty for displaced femoral neck fracture (FNF). Materials and Methods: We retrospectively reviewed 284 elderly patients who underwent hemiarthroplasty for Garden type IV FNF from September 2014 to September 2020. Using the receiver operating characteristic curve, optimal cutoff values for LCR, NLR, and albumin were established, and patients were categorized as low or high. Associations with 2-year mortality were evaluated through univariate and multivariate Cox regression analyses. Results: Of the 284 patients, 124 patients (45.9%) died within 2 years post-surgery. The optimal cutoff values were: LCR at 7.758 (specificity 58.5%, sensitivity 25.0%), NLR at 3.854 (specificity 39.2%, sensitivity 40.0%), and albumin at 3.750 (specificity 65.9%, sensitivity 21.9%). Patients with low LCR (<7.758), high NLR (≥3.854), and low albumin (<3.750) had a statistically significant reduced survival time compared to their counterparts. Conclusion: Lower preoperative LCR and albumin levels, along with higher NLR, effectively predict 2-year mortality and 30-day post-surgery complications in elderly patients with Garden type IV FNF undergoing hemiarthroplasty.