Deep Learning Based Automatic Segmentation of the Thoracic Aorta from Chest Computed Tomography in Healthy Korean Adults.

OBJECTIVE: Segmenting the aorta into zones based on anatomical landmarks is a current trend to better understand interventions for aortic dissection or aneurysm. However, comprehensive reference values for aortic zones are lacking. The aim of this study was to establish reference values for aortic size using a fully automated deep learning based segmentation method. METHODS: This retrospective study included 704 healthy adults (mean age 50.6 ± 7.5 years; 407 [57.8%] males) who underwent contrast enhanced chest computed tomography (CT) for health screening. A convolutional neural network (CNN) was trained and applied on 3D CT images for automatic segmentation of the aorta based on the Society for Vascular Surgery/Society of Thoracic Surgeons classification. The CNN generated masks were reviewed and corrected by expert cardiac radiologists. RESULTS: Aortic size was significantly larger in males than in females across all zones (zones 0 - 8, all p < .001). The aortic size in each zone increased with age, by approximately 1 mm per 10 years of age, e.g., 25.4, 26.7, 27.5, 28.8, and 29.8 mm at zone 2 in men in the age ranges of 30 - < 40, 40 - < 50, 50 - < 60, 60 - < 70, and ≥ 70 years, respectively (all p < .001). CONCLUSION: The deep learning algorithm provided reliable values for aortic size in each zone, with automatic masks comparable with manually corrected ones. Aortic size was larger in males and increased with age. These findings have clinical implications for the detection of aortic aneurysms or other aortic diseases.

Systematic Proteome Profiling of Maternal Plasma for Development of Preeclampsia Biomarkers.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. METHODS: Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver operating characteristics curve (AUC). RESULTS: A total of 1,307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Up-regulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC > 0.9 and P < 0.001, for all) as validated by MRM and ELISA. CONCLUSIONS: Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women.

PET imaging of colon cancer CD73 expression using cysteine site-specific 89Zr-labeled anti-CD73 antibody.

CD73 is a cell-surface ectoenzyme that hydrolyzes the conversion of extracellular adenosine monophosphate to adenosine, which in turn can promote resistance to immune checkpoint blockade therapy. Immune response may therefore be improved by targeting tumor CD73, and this possibility underlines the need to non-invasively assess tumor CD73 level. In this study, we developed a cysteine site-specific 89Zr-labeled anti-CD73 (89Zr-CD73) IgG immuno-PET technique that can image tumor CD73 expression in living bodies. Anti-CD73 IgG was reduced with tris(2-carboxyethyl)phosphine, underwent sulfohydryl moiety-specific conjugation with deferoxamine-maleimide, and was radiolabeled with 89Zr. CT26 mouse colon cancer cells, CT26/CD73 cells engineered to constitutively overexpress CD73, and 4T1.2 mouse breast cancer cells underwent cell binding assays and western blotting. Balb/c nude mice bearing tumors underwent 89Zr-CD73 IgG PET imaging and biodistribution studies. 89Zr-CD73 IgG showed 20-fold higher binding to overexpressing CT26/CD73 cells compared to low-expressing CT26 cells, and moderate expressing 4T1.2 cells showed uptake that was 38.9 ± 1.51% of CT26/CD73 cells. Uptake was dramatically suppressed by excess unlabeled antibody. CD73 content proportionately increased in CT26 and CT26/CD73 cell mixtures was associated with linear increases in 89Zr-CD73 IgG uptake. 89Zr-CD73 IgG PET/CT displayed clear accumulation in CT26/CD73 tumors with greater uptake compared to CT26 tumors (3.13 ± 1.70%ID/g vs. 1.27 ± 0.31%ID/g at 8 days; P = 0.04). Specificity was further supported by low CT26/CD73 tumor-to-blood ratio of 89Zr-isotype-IgG compared to 89Zr-CD73 IgG (0.48 ± 0.08 vs. 2.68 ± 0.52 at 4 days and 0.53 ± 0.07 vs. 4.81 ± 1.02 at 8 days; both P < 0.001). Immunoblotting and immunohistochemistry confirmed strong CD73 expression in CT26/CD73 tumors and low expression in CT26 tumors. 4T1.2 tumor mice also showed clear 89Zr-CD73 IgG accumulation at 8 days (3.75 ± 0.70%ID/g) with high tumor-to-blood ratio compared to 89Zr-isotype-IgG (4.91 ± 1.74 vs. 1.20 ± 0.28; P < 0.005). 89Zr-CD73 IgG specifically targeted CD73 on high expressing cancer cells in vitro and tumors in vivo. Thus, 89Zr-CD73 IgG immuno-PET may be useful for the non-invasive monitoring of CD73 expression in tumors of living subjects.

Severe acquired hemophilia A associated with COVID-19 vaccination: A case report and literature review.

RATIONALE: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an antibody that inhibits coagulation factor VIII activity. More than half of patients with AHA cannot identify underlying disorders. The remaining patients are associated with malignancies, autoimmune diseases, skin diseases, infections, and medications. Here, we present a case of 56-year-old Korean man with underlying hypertension, dyslipidemia, and diabetes mellitus who developed AHA following the second dose of BNT162b2 COVID-19 vaccination. PATIENT CONCERNS: He presented with a large 20 × 30 cm-sized hematoma along the psoas muscle and intracranial hemorrhage, necessitating intensive care with mechanical ventilation and continuous renal replacement therapy. Laboratory testing demonstrated that activated partial thromboplastin time and prothrombin times were 74.7 seconds (normal range 29-43 seconds) and 17.2 seconds (normal range 12.5-14.7 seconds), respectively. DIAGNOSES: Laboratory tests confirmed AHA with undetectable factor VIII activity (<1.5%) and a positive factor VIII antibody with a titer of 8.49 Bethesda units/mL. INTERVENTIONS: Recombinant factor VIIa (NovoSeven®) was administered every 2 hours to control the bleeding, alongside immunosuppression with methylprednisolone 1 mg/kg daily and cyclophosphamide 2 mg/kg daily to eliminate the autoantibody. OUTCOMES: Despite the treatments, the patient developed sepsis and succumbed 14 weeks after admission. LESSONS: This rare case underscores the importance of monitoring for AHA following COVID-19 vaccination. Although the benefits outweigh the risks of vaccination, AHA should be considered in the differential diagnosis of unusual bleeding following the vaccinations. Early diagnosis and management before severe bleeding are critical for successfully controlling life-threatening bleeding.

The effect of non-steroidal anti-inflammatory drugs on postoperative delirium: a meta-analysis.

Background: Neuroinflammation is postulated as a potential mechanism underlying postoperative delirium. This study aimed to investigate the impact of non-steroidal anti-inflammatory drug (NSAID) use on postoperative delirium. Methods: We conducted a literature search in electronic databases, including PubMed, EMBASE, CENTRAL, and Web of Science, to identify eligible randomized controlled studies. The primary outcome was the incidence of postoperative delirium, and the secondary outcomes included pain scores and the amounts of opioid used at 24 h postoperatively. We estimated the effect size through calculating the odds ratios (ORs) or mean differences (MDs) with 95% CIs, as appropriate. Results: In the analysis of eight studies involving 1,238 participants, the incidence of postoperative delirium was 11% and 19% in the NSAID and control groups, respectively, with a significant reduction in the NSAID group (OR, 0.54; 95% CI, 0.38 to 0.76; P = 0.0001; I2 = 0%). NSAID use had a significant effect on postoperative pain reduction (MD, -0.75; 95% CI, -1.37 to -0.13; P = 0.0172; I2 = 88%). Significant lower postoperative opioid consumption was observed in the NSAID group (MD, -2.88; 95% CI, -3.54 to -2.22; P = 0.000; I2 = 0%). Conclusions: NSAID administration reduced the incidence of postoperative delirium, severity of pain, and opioid dose used.

Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer.

Background: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. Methods: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. Results: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. Conclusions: These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Nurses' perspectives about end-of-life care when family presence is restricted during a pandemic: A qualitative study.

BACKGROUND: To prevent the infection from spreading, patients who were dying from COVID-19 were treated in isolation with restricted family access, which differed from existing end-of-life care procedures. This was a significant change that affected the care provided by nurses. OBJECTIVES: This study explored nurses' end-of-life care experiences in a limited family visitation setting during the COVID-19 pandemic. METHODS: A descriptive qualitative study was conducted. Data were collected through individual, in-depth, semistructured interviews with ten critical care nurses who provided end-of-life care to patients with COVID-19 in South Korea. The data were analysed using thematic analysis. The Consolidated Criteria for Reporting Qualitative Research checklist was used to assess the study's rigour. FINDINGS: Three themes were identified: 'Witnessing patients' and families' heartbreak over separation', 'The gaps between the ideals and realities of end-of-life care', and 'Efforts to provide patients with a comfortable final journey'. Nurses realise the importance of their central role in supporting interactions between patients and families during end-of-life care. CONCLUSIONS: Family participation, facilitated by nurses' interest and efforts as mediators connecting patients and families, is essential for achieving high-quality care for inpatients facing end of life. This study is significant as it emphasises that the direction of end-of-life care should be family centric, even in a pandemic situation with limited family participation. To improve interaction between patients and families, creating an environment based on family participation that builds trust and strengthens communication is essential. Additionally, hospital support, such as professional education and counselling, should be provided to strengthen nurses' end-of-life care competency.

Enterohemorrhagic Escherichia coli (EHEC) disrupts intestinal barrier integrity in translational canine stem cell-derived monolayers.

This study addresses the gap in translatable in vitro models for investigating Enterohemorrhagic E. coli (EHEC) infections, particularly relevant to both canine and human health. EHEC is known to induce acute colitis in dogs, leading to symptoms like hemorrhagic diarrhea and hemolytic uremic syndrome, similar to those observed in humans. However, understanding the pathophysiology and developing treatment strategies have been challenging due to the lack of effective models that replicate the clinical disease caused by EHEC in both species. Our approach involved the development of colonoid-derived monolayers using intestinal tissues from healthy, client-owned dogs. These monolayers were exposed to EHEC, and the impact of EHEC was assessed through several techniques, including trans-epithelial electrical resistance (TEER) measurement, immunofluorescence staining for junction proteins and mucus, and scanning electron microscopy for morphological analysis. Modified culture with saline, which was intended to prevent bacterial overgrowth, maintained barrier integrity and cell differentiation. EHEC infection led to significant decreases in TEER and ZO-1 expression, but not in E-cadherin levels or mucus production. In addition, EHEC elicited a notable increase in tumor necrosis factor-alpha production, highlighting its distinct impact on canine intestinal epithelial cells compared to non-pathogenic E. coli. These findings closely replicate in vivo observations in dogs and humans with EHEC enteropathy, validating the canine colonoid-derived monolayer system as a translational model to study host-pathogen interactions in EHEC and potentially other clinically significant enteric pathogens. IMPORTANCE: This study develops a new model to better understand Enterohemorrhagic E. coli (EHEC) infections, a serious bacterial disease affecting both dogs and humans, characterized by symptoms such as hemorrhagic diarrhea and hemolytic uremic syndrome. Traditional research models have fallen short of mimicking how this disease manifests in patients. Our research used intestinal tissues from healthy dogs to create layers of cells, known as colonoid-derived monolayers, which we then exposed to EHEC. We assessed the damage caused by the bacteria using several techniques, observing significant changes similar to those seen in actual cases of the disease. The model proved effective in replicating the interaction between the host and the pathogen, marking an important step toward understanding EHEC's effects and developing treatments. This canine colonoid-derived monolayer system not only bridges a crucial gap in current research but also offers a promising platform for studying other enteric pathogens affecting both canine and human health.

A Pressure-Sensitive, Repositionable Bioadhesive for Instant, Atraumatic Surgical Application on Internal Organs.

Pressure-sensitive adhesives are widely utilized due to their instant and reversible adhesion to various dry substrates. Though offering intuitive and robust attachment of medical devices on skin, currently available clinical pressure-sensitive adhesives do not attach to internal organs, mainly due to the presence of interfacial water on the tissue surface that acts as a barrier to adhesion. In this work, a pressure-sensitive, repositionable bioadhesive (PSB) that adheres to internal organs by synergistically combining the characteristic viscoelastic properties of pressure-sensitive adhesives and the interfacial behavior of hydrogel bioadhesives, is introduced. Composed of a viscoelastic copolymer, the PSB absorbs interfacial water to enable instant adhesion on wet internal organs, such as the heart and lungs, and removal after use without causing any tissue damage. The PSB's capabilities in diverse on-demand surgical and analytical scenarios including tissue stabilization of soft organs and the integration of bioelectronic devices in rat and porcine models, are demonstrated.

Visceral adiposity is associated with iron deposition and myelin loss in the brains of aged mice.

Iron deposition and myelin loss are observed in the brain with aging, and iron accumulation is suggested to be involved in myelin damage. However, the exact mechanism of iron deposition with aging remains unclear. This study was aimed to determine whether expanded visceral adipose tissue contributes to iron deposition and myelin loss by inducing hepcidin in the brains of aged male mice. Compared with young adult mice, levels of hepcidin in the brain, epididymal adipose tissue, and circulation were increased in aged mice, which had expanded visceral adipose tissue with inflammation. An increase in expressions of ferritin, an indicator of intracellular iron status, was accompanied by decreased levels of proteins related to myelin sheath in the brains of aged mice. These age-related changes in the brain were improved by visceral fat removal. In addition, IL-6 level, activation of microglia/macrophages, and nuclear translocation of phosphorylated Smad1/5 (pSmad1/5) inducing hepcidin expression were reduced in the brains of aged mice after visceral fat removal, accompanied by decreases of pSmad1/5- and ferritin-positive microglia/macrophages and mature oligodendrocytes. These findings indicate that visceral adiposity contributes to hepcidin-mediated iron deposition and myelin loss with inflammation in the aged brain. Our results support the importance of preventing visceral adiposity for maintaining brain health in older individuals.

iRhom2 deficiency reduces sepsis-induced mortality associated with the attenuation of lung macrophages in mice.

Sepsis has a high mortality rate and leads to multi-organ failure, including lung injury. Inactive rhomboid protease family protein (iRhom2) has been identified as accountable for the release of TNF-α, a crucial mediator in the development of sepsis. This study aimed to evaluate the role of iRhom2 in sepsis and sepsis-induced acute lung injury (ALI). TNF-α and IL-6 secretion in vitro by peritoneal macrophages from wild-type (WT) and iRhom2 knoukout (KO) mice was assessed by enzyme-linked immunosorbent assay. Cecal ligation and puncture (CLP)-induced murine sepsis model was used for in vivo experiments. To evaluate the role of iRhom2 deficiency on survival during sepsis, both WT and iRhom2 KO mice were monitored for 8 consecutive days following the CLP. For histologic and biochemical examination, the mice were killed 18 h after CLP. iRhom2 deficiency improved the survival of mice after CLP. iRhom2 deficiency decreased CD68+ macrophage infiltration in lung tissues. Multiplex immunohistochemistry revealed that the proportion of Ki-67+ CD68+ macrophages was significantly lower in iRhom2 KO mice than that in WT mice after CLP. Moreover, CLP-induced release of TNF-α and IL-6 in the serum were significantly inhibited by iRhom2 deficiency. iRhom2 deficiency reduced NF-kB p65 and IκBα phosphorylation after CLP. iRhom2 deficiency reduces sepsis-related mortality associated with attenuated macrophage infiltration and proliferation in early lung injury. iRhom2 may play a pivotal role in the pathogenesis of sepsis and early stage of sepsis-induced ALI. Thus, iRhom2 may be a potential therapeutic target for the management of sepsis and sepsis-induced ALI.

Launch of the first canine mobile blood donation center in Asia: development, outcomes, and influence of an animal bloodmobile.

Introduction: A mobile blood donation station allows a maximum number of donors to donate blood at any location. In veterinary medicine, no previous studies have reported the use of bloodmobiles for blood donation in animals. We assessed Asia's first canine mobile blood donation center, which was trialed using a modified vehicle in South Korea. Methods: A vehicle was modified into a canine bloodmobile with two sections: the front as a laboratory and the back as a blood collection room with necessary equipment. To recruit companion dogs nationwide, the campaign was advertised on television and promoted via social media. Applications of the dogs meeting the following criteria were accepted: in general good health, between 2-8 years old, body weight above 25kg, vaccinated, regularly on heartworm and ectoparasite prophylactics. Pre-donation procedures included medical screening and informed consent, followed by blood collection in a routine fashion. Post-donation, dogs were monitored for complications and owners completed a post-donation survey. Results: Of the 750 applicants, 48 donor dogs were selected for investigation. Ten failed to donate blood owing to the following issues: behavioral problems (2/48), positive results on vector-borne disease screening tests (5/48), in-tubing clot formation (2/48), and absence on the relevant appointment date (1/48). Blood collection took approximately 12 minutes, and the entire procedure lasted an average of 1.5 hours per donor. The prevalence rates of dog erythrocyte antigen 1-negative and 1-positive blood were 32.6% and 67.4%, respectively. There were no donation-related complications, except for one dog that had contact dermatitis induced by clipper irritation. The post-donation survey completed by 46 owners revealed that most were satisfied with the campaign. The convenience of the mobile blood drive (93.5%) was a key factor contributing to high owner satisfaction and willingness to participate in future campaigns (95.7%), in line with findings from prior veterinary and human blood donation motivation research. Discussion: The bloodmobile effectively increased engagement in canine blood donation by enhancing accessibility. To optimize canine mobile blood drives, procuring larger vehicles and enhancing infrastructure for future campaigns would be beneficial. In conclusion, this study showed that Asia's first canine bloodmobile was successful in terms of improving the convenience, accessibility, and efficacy of canine blood donation. Although the concept is still unfamiliar to the public, active promotion of canine blood donation can help ensure a robust blood donation culture in the veterinary field.

The effect of remote ischemic conditioning on mortality after kidney transplantation: the systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Ischemic-reperfusion injury resulting from kidney transplantation declines the post-transplant graft function. Remote ischemic conditioning (RIC) is known to be able to reduce the criticality of ischemic reperfusion injury. This study aimed to meta-analyze whether the application of remote ischemic conditioning to kidney transplantation patients improves clinical outcomes. METHODS: Researchers included randomized controlled studies of the application of RIC to either kidney donors or recipients. Articles were retrieved from PubMed, Embase, Web of Science, and Cochrane Library. The risk of bias was evaluated using RoB 2.0. The primary outcome was mortality after transplantation. Secondary outcomes were the incidence of delayed graft function, graft rejection, and post-transplant laboratory results. All outcomes were integrated by RevMan 5.4.1. RESULTS: Out of 90 papers, 10 articles (8 studies, 1977 patients) were suitable for inclusion criteria. Mortality collected at all time points did not show a significant difference between the groups. Three-month mortality (RR, 3.11; 95% CI, 0.13-75.51, P = 0.49) tended to increase in the RIC group, but 12-month (RR, 0.70; 95% CI, 0.14-3.45, P = 0.67) or final-reported mortality (RR, 0.49; 95% CI, 0.23-1.06, P = 0.07) was higher in the sham group than the RIC group. There was no significant difference between the RIC and sham group in delayed graft function (RR, 0.64; 95% CI, 0.30-1.35, P = 0.24), graft rejection (RR, 1.13; 95% CI, 0.73-1.73, P = 0.59), and the rate of time required for a 50% reduction in baseline serum creatinine concentration of less than 24 h (RR, 0.98; 95% CI, 0.61-1.56, P = 0.93). CONCLUSIONS: It could not be concluded that the application of RIC is beneficial to kidney transplantation patients. However, it is noteworthy that long-term mortality tended to decrease in the RIC group. Since there were many limitations due to the small number of included articles, researchers hope that large-scale randomized controlled trials will be included in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022336565.

Hypertrophic cardiomyopathy detection with artificial intelligence electrocardiography in international cohorts: an external validation study.

Aims: Recently, deep learning artificial intelligence (AI) models have been trained to detect cardiovascular conditions, including hypertrophic cardiomyopathy (HCM), from the 12-lead electrocardiogram (ECG). In this external validation study, we sought to assess the performance of an AI-ECG algorithm for detecting HCM in diverse international cohorts. Methods and results: A convolutional neural network-based AI-ECG algorithm was developed previously in a single-centre North American HCM cohort (Mayo Clinic). This algorithm was applied to the raw 12-lead ECG data of patients with HCM and non-HCM controls from three external cohorts (Bern, Switzerland; Oxford, UK; and Seoul, South Korea). The algorithm's ability to distinguish HCM vs. non-HCM status from the ECG alone was examined. A total of 773 patients with HCM and 3867 non-HCM controls were included across three sites in the merged external validation cohort. The HCM study sample comprised 54.6% East Asian, 43.2% White, and 2.2% Black patients. Median AI-ECG probabilities of HCM were 85% for patients with HCM and 0.3% for controls (P < 0.001). Overall, the AI-ECG algorithm had an area under the receiver operating characteristic curve (AUC) of 0.922 [95% confidence interval (CI) 0.910-0.934], with diagnostic accuracy 86.9%, sensitivity 82.8%, and specificity 87.7% for HCM detection. In age- and sex-matched analysis (case-control ratio 1:2), the AUC was 0.921 (95% CI 0.909-0.934) with accuracy 88.5%, sensitivity 82.8%, and specificity 90.4%. Conclusion: The AI-ECG algorithm determined HCM status from the 12-lead ECG with high accuracy in diverse international cohorts, providing evidence for external validity. The value of this algorithm in improving HCM detection in clinical practice and screening settings requires prospective evaluation.

Preoperative gastric volume assessment using ultrasound in cerebral palsy pediatric patients: a prospective observational study.

BACKGROUND: Although cerebral palsy is a risk factor for aspiration, there is insufficient research on residual gastric volume after preoperative fasting in children with cerebral palsy. We evaluated the incidence of a full stomach by ultrasound assessment of the gastric volume in children with cerebral palsy who underwent orthopedic surgery after preoperative fasting. METHODS: The patients fasted for 8 h for solid foods and 2 h for clear liquids. We obtained the gastric antral cross-sectional area using ultrasound in the semi-recumbent and right lateral decubitus positions. A calculated stomach volume > 1.5 mL.kg-1 was considered as full, which poses a high aspiration risk. The primary outcome was the incidence of full stomach, and the secondary outcomes were the qualitative gastric volume, correlation of disease severity categorized according to the Gross Motor Function Classification System with the residual gastric volume, gastric volume per body weight, and qualitative gastric volume. RESULTS: Thirty-seven pediatric patients with cerebral palsy, scheduled for elective orthopedic surgery, were included for analysis. Full-stomach status was observed in none, and the gastric volume per body weight was 0.5 (0.4-0.7) mL.kg-1. No significant differences were observed in the residual gastric volume (p = 0.114), gastric volume per body weight (p = 0.117), or qualitative grade of gastric volume (p = 0.642) in relation to disease severities. CONCLUSION: Children with cerebral palsy who fasted preoperatively had empty or nearly empty stomachs. Further studies are required to determine the optimal fasting duration for such children.

Familial clustering of dysbiotic oral and fecal microbiomes in juvenile dermatomyositis.

Juvenile dermatomyositis (JDM) is a rare immune-mediated disease of childhood with putative links to microbial exposures. In this multi-center, prospective, observational cohort study, we evaluated whether JDM is associated with discrete oral and gut microbiome signatures. We generated 16S rRNA sequencing data from fecal, saliva, supragingival, and subgingival plaque samples from JDM probands (n = 28). To control for genetic and environmental determinants of microbiome community structure, we also profiled microbiomes of unaffected family members (n = 27 siblings, n = 26 mothers, and n = 17 fathers). Sample type (oral-vs-fecal) and nuclear family unit were the predominant variables explaining variance in microbiome diversity, more so than having a diagnosis of JDM. The oral and gut microbiomes of JDM probands were more similar to their own unaffected siblings than they were to the microbiomes of other JDM probands. In a sibling-paired within-family analysis, several potentially immunomodulatory bacterial taxa were differentially abundant in the microbiomes of JDM probands compared to their unaffected siblings, including Faecalibacterium (gut) and Streptococcus (oral cavity). While microbiome features of JDM are often shared by unaffected family members, the loss or gain of specific fecal and oral bacteria may play a role in disease pathogenesis or be secondary to immune dysfunction in susceptible individuals.

Assessing the Efficacy of Acanthoic Acid Isolated from Acanthopanax koreanum Nakai in Male Infertility: An In Vivo and In Silico Approach.

Acanthoic acid, a diterpene isolated from the root bark of Acanthopanax koreanum Nakai, possesses diverse pharmacological activities, including anti-inflammatory, anti-diabetic, gastrointestinal protection, and cardiovascular protection. This study is the first to investigate the egg-hatching rates of Drosophila melanogaster affected by acanthoic acid. Notably, male flies supplemented with 10 µM acanthoic acid exhibited a strong increase in hatching rates compared with controls under adverse temperature conditions, suggesting a potential protective effect against environmental stressors. Molecular docking simulations revealed the binding affinities and specific interactions between acanthoic acid and proteins related to male infertility, including SHBG, ADAM17, and DNase I, with binding affinity values of -10.2, -6.8, and -5.8 kcal/mol, respectively. Following the docking studies, molecular dynamic simulations were conducted for a duration of 100 ns to examine the stability of these interactions. Additionally, a total binding energy analysis and decomposition analysis offered insights into the underlying energetic components and identified key contributing residues.

Association of Fibrate use with clinical expression of hypertrophic cardiomyopathy.

AIMS: An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. METHODS: We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate-user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate-naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. RESULTS: During a median follow-up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630-0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553-0.934) and 0.655 (0.492-0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591-0.929) and 0.750 (0.609-0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. CONCLUSION: The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours.

Stress resistance insights of 65 Listeria strains: Acidic, low temperature, and high salt environments.

Genetically, Listeria monocytogenes is closely related to non-L. monocytogenes (L. innocua, L. welshimeri, L. grayi, L. aquatica, and L. fleischimannii). This bacterium is well known for its resistance to harsh conditions including acidity, low temperatures, and high salt concentrations. This study explored the responses of 65 Listeria strains to stress conditions and characterized the prevalence of stress-related genes. The 65 Listeria strains were isolated from different environments and their viability was assessed in four different tests: independent tests for pH 3, 1 °C, and 5 % salt concentration and multiple resistance tests that combined pH 3, 1 °C, 5 % salt. From the data, the 65 strains were categorized into stress-resistant (56) or stress-sensitive groups (9), with approximately 4 log CFU/mL differences. The PCR assay analyzed the prevalence of two virulence genes prfA and inlA, and eight stress-related genes: three acid (gadB, gadC, and atpD), two low temperature (betL and opuCA) and three salt resistance genes (flaA, cysS, and fbp). Two low temperature (bet and opuCA) and salt resistance (fbp) genes were more prevalent in the stress-resistant strains than in the stress-sensitive Listeria group.

Alpha-galactosylceramide pre-treatment attenuates clinical symptoms of LPS-induced acute neuroinflammation by converting pathogenic iNKT cells to anti-inflammatory iNKT10 cells in the brain.

BACKGROUND: Invariant natural killer T (iNKT) cells play protective or pathogenic roles in a variety of immune and inflammatory diseases. However, whether iNKT cells contribute to the progression of acute neuroinflammation remains unclear. Thus, we addressed this question with a mouse model of lipopolysaccharide (LPS)-induced acute neuroinflammation. METHODS: For induction of acute neuroinflammation, wild-type (WT) C57BL/6 (B6) mice were injected intraperitoneally (i.p.) with LPS for either three or five consecutive days, and then these mice were analyzed for brain-infiltrating leukocytes or mouse behaviors, respectively. To examine the role of iNKT cell activation in LPS-induced neuroinflammation, mice were injected i.p. with the iNKT cell agonist α-galactosylceramide (α-GalCer) seven days prior to LPS treatment. Immune cells infiltrated into the brain during LPS-induced neuroinflammation were determined by flow cytometry. In addition, LPS-induced clinical behavior symptoms such as depressive-like behavior and memory impairment in mice were evaluated by the open field and Y-maze tests, respectively. RESULTS: We found that iNKT cell-deficient Jα18 mutant mice display delayed disease progression and decreased leukocyte infiltration into the brain compared with WT mice, indicating that iNKT cells contribute to the pathogenesis of LPS-induced neuroinflammation. Since it has been reported that pre-treatment with α-GalCer, an iNKT cell agonist, can convert iNKT cells towards anti-inflammatory phenotypes, we next explored whether pre-activation of iNKT cells with α-GalCer can regulate LPS-induced neuroinflammation. Strikingly, we found that α-GalCer pre-treatment significantly delays the onset of clinical symptoms, including depression-like behavior and memory impairment, while decreasing brain infiltration of pro-inflammatory natural killer cells and neutrophils, in this model of LPS-induced neuroinflammation. Such anti-inflammatory effects of α-GalCer pre-treatment closely correlated with iNKT cell polarization towards IL4- and IL10-producing phenotypes. Furthermore, α-GalCer pre-treatment restored the expression of suppressive markers on brain regulatory T cells during LPS-induced neuroinflammation. CONCLUSION: Our findings provide strong evidence that α-GalCer-induced pre-activation of iNKT cells expands iNKT10 cells, mitigating depressive-like behaviors and brain infiltration of inflammatory immune cells induced by LPS-induced acute neuroinflammation. Thus, we suggest the prophylactic potential of iNKT cells and α-GalCer against acute neuroinflammation.