Synergistic efficacy of ultrasound and ammonium persulfate in inactivating Escherichia coli O157:H7 in buffered peptone water and orange juice.

This study investigated the synergistic effects of ammonium persulfate (PS) and ultrasound (US) on the inactivation of Escherichia coli O157:H7 in buffered peptone water (BPW) and orange juice products. A comprehensive assessment of PS concentrations ranging from 1 to 300 mM, considering not only the statistical significance but also the reliability and stability of the experimental outcomes, showed that 150 mM was the optimal PS concentration for the inactivation of E. coli O157:H7. Additionally, US output intensities varying from 30 % to 60 % of the maximum US intensity were evaluated, and 50 % US amplitude was found to be the optimal US condition. A 50 % amplitude setting on the sonicator corresponds to half of its maximum displacement, approximately 60 µm, based on a maximum amplitude of 120 µm. The inactivation level of E. coli O157:H7 was significantly enhanced by the combined treatment of PS and US, compared to each treatment of PS and US alone. In the BPW, a 10-min treatment with the combination of PS and US resulted in a significant synergistic inactivation, achieving up to a log reduction of 3.86 log CFU/mL. Similarly, in orange juice products, a 5-min treatment with the combination of PS and US yielded a significant synergistic inactivation, with a reduction reaching 5.90 log CFU/mL. Although the treatment caused a significant color change in the sample, the visual differences between the treated and non-treated groups were not pronounced. Furthermore, the combined treatment in orange juice demonstrated significantly enhanced antimicrobial efficacy relative to BPW. Despite identical 5-min treatment periods, the application in orange juice resulted in a substantially higher log reduction of E. coli O157:H7, achieving 7.16 log CFU/mL at a reduced PS concentration of 30 mM, whereas the same treatment in BPW yielded only a 2.89 log CFU/mL reduction at a PS concentration of 150 mM, thereby highlighting its significantly superior antimicrobial performance in orange juice. The mechanism underlying microbial inactivation, induced by the combined treatment of PS and US, was identified as significant cell membrane damage. This damage is mediated by sulfate radicals, generated through the sono-activation of persulfate. In addition, the low pH of orange juice, measured at 3.7, is likely to have further deteriorated the E. coli O157:H7 cells compared to BPW (pH 7.2), by disrupting their cell membranes, proton gradients, and energy metabolism. These findings underscore the effectiveness of PS and US integration as a promising approach for non-thermal pasteurization in the food industry. Further research is needed to optimize treatment parameters and fully explore the practical application of this technique in large-scale food processing operations. Sensory evaluation and nutritional assessment are also necessary to address the limitations of PS.

The Barriers to Recognizing and Reporting Child Physical Abuse by Emergency Physicians and Associated Factors.

BACKGROUND: Although the reporting rate of child abuse is increasing every year, the child abuse detection rate is 3.81% as of 2019 in Korea, which is significantly lower than that of developed countries for child rights. OBJECTIVE: We investigated the associated factors with barriers that emergency physicians face in recognizing and reporting cases of child abuse. METHODS: From May to July 2022, 240 emergency physicians working in the 15 emergency department were asked to participate in the survey via email. The questionnaire included the respondent's basic information, treatment experience for child abuse, reasons for reporting or not reporting, and opinions on measures to increase the reporting rate. We conducted a logistic regression analysis to discern the factors contributing to underreporting. RESULTS: Seventy-one individuals were included in the analysis, after excluding those who had never encountered suspected cases of child abuse. A multivariable logistic regression was performed with the above variables, and although it was not statistically significant, there was a tendency for workers to report well when working at a pediatric emergency department (odds ratio [95% confidence interval], 3.97 [0.98-16.09]). The primary reason for reporting suspected abuse was the pattern of damage suspected of abuse. The first reason for not reporting suspected abuse was because they were not sure it was child abuse. Respondents answered that to report better, a quick and appropriate response from the police and confidentiality of the reporter were needed. CONCLUSIONS: Physicians in pediatric emergency departments demonstrated a tendency for more proactive reporting suspected cases of child abuse.

IL-27-induced PD-L1highSca-1+ innate lymphoid cells suppress contact hypersensitivity in an IL-10-dependent manner.

Innate lymphoid cells (ILCs) play an important role in maintaining tissue homeostasis and various inflammatory responses. ILCs are typically classified into three subsets, as is the case for T-cells. Recent studies have reported that IL-10-producing type 2 ILCs (ILC210s) have an immunoregulatory function dependent on IL-10. However, the surface markers of ILC210s and the role of ILC210s in contact hypersensitivity (CHS) are largely unknown. Our study revealed that splenic ILC210s are extensively included in PD-L1highSca-1+ ILCs and that IL-27 amplifies the development of PD-L1highSca-1+ ILCs and ILC210s. Adoptive transfer of PD-L1highSca-1+ ILCs suppressed oxazolone-induced CHS in an IL-10-dependent manner Taken together, our results demonstrate that ILC210s are critical for the control of CHS and suggest that ILC210s can be used as target cells for the treatment of CHS.

Ideal chest compression site for cardiopulmonary resuscitation in fontan circulation patients with dextrocardia.

BACKGROUND: We aimed to identify the ideal chest compression site for cardiopulmonary resuscitation (CPR) in patients with a single ventricle with dextrocardia corrected by Fontan surgery. METHODS: The most recent stored chest computed tomography images of all patients with a single ventricle who underwent Fontan surgery were retrospectively analysed. We reported that the ideal chest compression site is the largest part of the compressed single ventricle. To identify the ideal chest compression site, we measured the distance from the midline of the sternum to the point of the maximum sagittal area of the single ventricle as a deviation and calculated the area fraction of the compressed structures. RESULTS: 58 patients (67.2% male) were analysed. The mean right deviation from the midline of the sternum to the ideal compression site was similar to the mean sternum width (32.85 ± 15.61 vs. 31.05 ± 6.75 mm). When chest compression was performed at the ideal site, the area fraction of the single ventricle significantly increased by 7%, which was greater than that of conventional compression (0.15 ± 0.10 vs. 0.22 ± 0.11, P < 0.05). CONCLUSIONS: When performing CPR on a patient with Fontan circulation with dextrocardia, right-sided chest compression may be better than the conventional location.

The Association Between Inter-Hospital Transfers and the Prognosis of Pediatric Injury in the Emergency Department.

BACKGROUND: Inter-hospital transfers of severely injured patients are inevitable due to limited resources. We investigated the association between inter-hospital transfer and the prognosis of pediatric injury using the Korean multi-institutional injury registry. METHODS: This retrospective observational study was conducted from January 2013 to December 2017; data for hospitalized subjects aged < 18 years were extracted from the Emergency Department-based Injury in Depth Surveillance database, in which 22 hospitals are participating as of 2022. The survival rates of the direct transfer group and the inter-hospital transfer group were compared, and risk factors affecting 30-day mortality and 72- hour mortality were analyzed. RESULTS: The total number of study subjects was 18,518, and the transfer rate between hospitals was 14.5%. The overall mortality rate was 2.3% (n = 422), the 72-hour mortality was 1.7% (n = 315) and the 30-day mortality rate was 2.2% (n = 407). The Kaplan-Meier survival curve revealed a lower survival rate in the inter-hospital transfer group than in the direct visit group (log-rank, P < 0.001). Cox proportional hazards regression analysis showed that inter-hospital transfer group had a higher 30-day mortality rate and 72-hour mortality (hazard ratio [HR], 1.681; 95% confidence interval [CI], 1.232-2.294 and HR, 1.951; 95% CI, 1.299-2.930) than direct visit group when adjusting for age, sex, injury severity, and head injury. CONCLUSION: Among the pediatric injured patients requiring hospitalization, inter-hospital transfer in the emergency department was associated with the 30-day mortality rate and 72-hour mortality rate in Korea.

Unpowered scooter injuries in children and risk factors for traumatic brain injuries: An 8-year cross-sectional study using a national registry in South Korea.

INTRODUCTION: Head trauma accounts for a large proportion of unpowered scooter injuries in children. Traumatic brain injury (TBI) is the leading cause of considerable mortality and morbidity in children, who are the main users of unpowered scooters. The aim of this study was to explore the characteristics of unpowered scooter injuries in children and to identify predictors of the occurrence of TBI. METHODS: A multicentre observational retrospective study was conducted using the Emergency Department-based Injury In-depth Surveillance (EDIIS) database in South Korea. Children aged 2 to 18 years old with unpowered scooter injuries between 2011 and 2018 were eligible for inclusion in this study, and the primary outcome was TBI defined based on the International Classification of Diseases, 10th Revision (ICD-10) code. RESULTS: The annual rate of unpowered scooter injuries per 1,000 injured patients increased throughout the study period from 1.4 in 2011 to 16.4 in 2018 (P for trend < 0.001). Of the 3,892 children who had unpowered scooter injuries, 353 (9.2 %) had TBI. Children were at a higher risk of unpowered scooter TBI if they were aged between 2 and 5 years (adjusted odds ratio [aOR]: 1.37; 95 % confidence interval (CI): 1.09-1.73), were male (aOR: 1.45; 95 % CI: 1.14-1.86), were injured either on sidewalks (aOR: 1.80; 95 % CI: 1.20-2.70) or on driveways (aOR: 2.31; 95 % CI: 1.41-3.79), and experienced a fall (aOR: 1.98; 95 % CI: 1.15-3.43). Additionally, children injured after a blunt force were at a lower risk of TBI (aOR: 0.28; 95 % CI: 0.15-0.53). CONCLUSION: Unpowered scooter injuries in children are increasing in South Korea. It is essential for younger children riding unpowered scooters to wear helmets and for caregivers to actively supervise their children to prevent TBI.

Comparison of age-adjusted shock indices as predictors of injury severity in paediatric trauma patients immediately after emergency department triage: A report from the Korean multicentre registry.

INTRODUCTION: Shock index paediatric-adjusted (SIPA) was presented for early prediction of mortality and trauma team activation in paediatric trauma patients. However, the derived cut-offs of normal vital signs were based on old references. We established alternative SIPAs based on the other commonly used references and compared their predictive values. METHODS: We performed a retrospective review of all paediatric trauma patients aged 1-15 years in the Emergency Department (ED)-based Injury In-depth Surveillance (EDIIS) database from January 1, 2011 to December 31, 2019. A total of 4 types of SIPA values were obtained based on the references as follows: uSIPA based on the Nelson textbook of paediatrics 21st ed., SIATLS based on the ATLS 10th guideline, SIPALS based on the PALS 2020 guideline, and SIPA. In each SIPA group, the cut-off was established by dividing the group into 4 subgroups: toddler (age 1-3), preschooler (age 4-6), schooler (age 7-12), and teenager (age 13-15). We performed an ROC analysis and calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) to compare the predicted values of each SIPA in mortality, ICU admission, and emergent surgery or intervention. RESULTS: A total of 332,271 patients were included. The proportion of patients with an elevated shock index was 14.9 % (n = 49,347) in SIPA, 22.8 % (n = 75,850) in uSIPA, 0.3 % (n = 1058) in SIATLS, and 4.3 % (n = 14,168) in SIPALS. For mortality, uSIPA achieved the highest sensitivity (57.0 %; 95 % confidence interval 56.9 %-57.2 %) compared to SIPA (49.4 %, 95 % CI 49.2 %-49.5 %), SIATLS (25.5 %, 95 % CI 25.4 %-25.7 %), and SIPALS (43.8 %, 95 % CI 43.7 %-44.0 %), but there were no significant differences in the negative predictive value (NPV) or area under the curve (AUC). The positive predictive value (PPV) was highest in SIATLS (5.7 %, 95 % CI 5.6 %-5.8 %) compared to SIPA (0.2 %, 95 % CI 0.2 %-0.3 %), uSIPA (0.2 %, 95 % CI 0.2 %-0.2 %), and SIPALS (0.7 %, 95 % CI 0.7 %-0.8 %). The same findings were presented in ICU admission and emergent operation or intervention. CONCLUSION: The ATLS-based shock index achieved the highest PPV and specificity compared to SIPA, uSIPA, and SIPALS for adverse outcomes in paediatric trauma.

Magnetic Resonance Imaging Characteristics of a Lateral Ligament Injury in Acute Ankle Sprains Among Athletes.

Background: It is important to identify the location and pattern of lateral ligament injuries that are related to the development and prognosis of chronic ankle instability in athletes with ankle sprains. Purpose: To describe the location and pattern of lateral ligament injuries on magnetic resonance imaging (MRI) in elite-level or amateur athletes with acute ankle sprains and to further assess the risk of associated concomitant injuries. Study Design: Cross-sectional study; Level of evidence, 3. Methods: The anterior talofibular ligament (ATFL) and calcaneofibular ligament (CFL) of 110 athletes with an ankle lateral ligament injury (mean age, 24.7 years) were evaluated. MRI scans were evaluated for the location and pattern of ATFL and CFL tears such as sleeve avulsions as well as concomitant deltoid ligament injuries, bone contusions, and osteochondral lesions of the talus (OLTs). Results: On MRI, 52 (47.3%) athletes had an isolated ATFL tear, 56 (50.9%) athletes had both ATFL and CFL tears, and 2 (1.8%) athletes had an isolated CFL tear. ATFL injuries occurred at the fibula, midsubstance, and talus in approximately equal numbers, whereas the majority of CFL injuries occurred at the calcaneal insertion. Concomitant deltoid ligament injuries were identified in 18 (16.4%) athletes. In addition, concomitant bone contusions and OLTs were identified in 38 (34.5%) and 6 (5.5%) athletes, respectively. Using linear-by-linear analysis, CFL injuries correlated with concomitant deltoid ligament and bone injuries (P = .023 and P = .001, respectively) and a sleeve injury pattern (P = .005). Conclusion: After an acute ankle ligament rupture, almost all athletes involved in this study had injured their ATFL, and approximately 50% had a concomitant injury to the CFL. The rate of sleeve-type CFL injuries at the calcaneal insertion was high, and concomitant deltoid ligament injuries and OLTs were associated with this pattern of injury.

Ellagic Acid Prevented Dextran-Sodium-Sulfate-Induced Colitis, Liver, and Brain Injury through Gut Microbiome Changes.

Inflammatory bowel disease (IBD) affects millions of people worldwide and is considered a significant risk factor for colorectal cancer. Recent in vivo and in vitro studies reported that ellagic acid (EA) exhibits important antioxidant and anti-inflammatory properties. In this study, we investigated the preventive effects of EA against dextran sulfate sodium (DSS)-induced acute colitis, liver, and brain injury in mice through the gut-liver-brain axis. Acute colitis, liver, and brain injury were induced by treatment with 5% (w/v) DSS in the drinking water for 7 days. Freshly prepared EA (60 mg/kg/day) was orally administered, while control (CON) group mice were treated similarly by daily oral administrations with a vehicle (water). All the mice were euthanized 24 h after the final treatment with EA. The blood, liver, colon, and brain samples were collected for further histological and biochemical analyses. Co-treatment with a physiologically relevant dose (60 mg/kg/day) of EA for 7 days significantly reduced the DSS-induced gut barrier dysfunction; endotoxemia; and inflammatory gut, liver, and brain injury in mice by modulating gut microbiota composition and inhibiting the elevated oxidative and nitrative stress marker proteins. Our results further demonstrated that the preventive effect of EA on the DSS-induced IBD mouse model was mediated by blocking the NF-κB and mitogen-activated protein kinase (MAPK) pathway. Therefore, EA co-treatment significantly attenuated the pro-inflammatory and oxidative stress markers by suppressing the activation of NF-κB/MAPK pathways in gut, liver, and brain injury. These results suggest that EA, effective in attenuating IBD in a mouse model, deserves further consideration as a potential therapeutic for the treatment of inflammatory diseases.

Pomegranate-Derived Exosome-Like Nanovesicles Alleviate Binge Alcohol-Induced Leaky Gut and Liver Injury.

Alcoholic liver disease (ALD) is damage to the liver and mainly caused by binge alcohol. ALD have decreased junctional protein expression and modulated intestinal permeability. We investigated whether plant-releasing exosome-like nanovesicles can prevent liver damage and leaky gut from binge alcohol. In this study, we characterized the exosome-like nanovesicles from pomegranate juice and confirmed the round shape of a lipid bilayer. After 14 days of pomegranate-derived exosome-like nanovesicle (PNVs) pretreatment, binge alcohol (6 g/kg/dose) was administered to mice three times orally every 12 h. Exposure to binge alcohol increased levels of oxidative and nitric oxide stress marker proteins such as CYP2E1, 3-Nitrotyrosine, and inducible nitric oxide synthase in both liver and gut damage. Also, binge alcohol significantly elevated the plasma endotoxemia, inflammatory fatty liver, and leaky gut. However, PNVs reduced the oxidative stress and apoptosis marker proteins and prevented the leaky gut and endotoxemia. Markedly, PNV treatment significantly prevented a decrease in the amount of intestinal junctional proteins and an increase in leaky gut in mice exposed to alcohol. These results showed that PNVs can prevent leaky gut and liver damage caused by binge alcohol and suggest that it may be useful hepatoprotective or intestinal protective agents for the first time.

A case series: patients with complicated popliteal artery entrapment syndrome successfully treated with a hybrid surgical and interventional treatment.

Background: Popliteal artery entrapment syndrome (PAES) is an underreported and underdiagnosed condition that affects the lower extremities. Previous case reports mainly presented young and uncomplicated PAES. Here, we report the cases of complicated PAES in middle-aged patients. Furthermore, we discuss the importance of a multidisciplinary team approach from diagnosis to treatment to obtain favourable clinical outcomes against this rare disease. Case summary: Two middle-aged patients presented with recent claudication and were diagnosed with popliteal artery obstruction due to a complicated PAES. At the multidisciplinary meeting, the decided treatment plan was to prioritize the gastrocnemius tendon accessory transfer and surgical thromboendarterectomy. In case the popliteal artery patency was unsatisfactory, an additional on-site percutaneous intervention was planned. Follow-up lower extremity computed tomographic angiography showed a patent popliteal artery without any claudication in both two cases. Discussion: Popliteal artery entrapment syndrome is a rare vascular disorder. Clinical suspicion and advanced imaging modalities can lead to an accurate diagnosis. A multidisciplinary team approach helps in obtaining favourable clinical results using minimally invasive hybrid surgical and interventional treatments.

Fast and Durable Nanofiber Mat Channel Organic Electrochemical Transistors.

Bioelectronic devices that offer real-time measurements, biological signal processing, and continuous monitoring while maintaining stable performance are in high demand. The materials used in organic electrochemical transistors (OECTs) demonstrate high transconductance (GM) and excellent biocompatibility, making them suitable for bioelectronics in a biological environment. However, ion migration in OECTs induces a delayed response time and low cut-off frequency, and the adverse biological environment causes OECT durability problems. Herein, we present OECTs with a faster response time and improved durability, made possible by using a nanofiber mat channel of a conventional OECT structure. Poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS)/polyacrylamide (PAAm) nanofiber mat channel OECTs are fabricated and subjected to various durability tests for the first time based on continuous measurements and mechanical stability assessments. The results indicate that the nanofiber mat channel OECTs have a faster response time and longer life spans compared to those of film channel OECTs. The improvements can be attributed to the increased surface area and fibrous structure of the nanofiber mat channel. Furthermore, the hydrogel helps to maintain the structure of the nanofiber, facilitates material exchange, and eliminates the need for a crosslinker.

Outcomes After Superior Capsular Reconstruction With an Achilles Tendon-Bone Allograft Using the Modified Keyhole Technique: A 2-Year Follow-up of a Novel Technique for Irreparable Rotator Cuff Tears.

Background: Despite improved outcomes, failure or nonhealing of graft materials has been reported after superior capsular reconstruction (SCR) for massive irreparable rotator cuff tears. Purpose: To evaluate the short-term clinical and radiological outcomes of a novel technique for SCR using an Achilles tendon-bone allograft. Study Design: Case series; Level of evidence, 4. Methods: We performed a retrospective review of patients who underwent SCR using an Achilles tendon-bone allograft with the modified keyhole technique and who had a minimum follow-up of 2 years. The visual analog scale score for pain, American Shoulder and Elbow Surgeons score, and Constant score were evaluated as subjective outcomes, while range of motion of the shoulder joint and isokinetic strength were evaluated as objective outcomes. The acromiohumeral interval (AHI), bone-to-bone healing of the allograft and humeral head on computed tomography, and graft integrity on magnetic resonance imaging were evaluated as radiological outcomes. Results: This study included 32 patients with a mean age of 56.8 ± 4.2 years and a mean follow-up of 28.4 ± 6.2 months. A significant improvement from preoperatively to the last follow-up was seen in the mean visual analog scale score for pain (from 6.7 to 1.8), American Shoulder and Elbow Surgeons score (from 42.7 to 83.8), Constant score (from 47.2 to 78.5), and AHI (from 4.8 to 8.2 mm) (P < .001 for all) as well as range of motion in forward elevation and internal rotation (P < .001 for both). Medial-to-lateral graft integrity was good in all patients. Nonunion at the fitting zone of the keyhole on the greater tuberosity was diagnosed in 1 case (3.1%), and failure of incorporation between the allograft and remnant tendon at the site of posterior margin convergence was observed in 4 cases (12.5%). Conclusion: The outcomes after SCR using an Achilles tendon-bone allograft and the keyhole technique improved, with an increased AHI and excellent integrity in the medial and lateral directions compared with preoperatively. This technique is a reasonable option for the surgical treatment of irreparable rotator cuff tears.

Plum-Derived Exosome-like Nanovesicles Induce Differentiation of Osteoblasts and Reduction of Osteoclast Activation.

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 µg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.

Brain natriuretic peptide as a clinical screening tool for the diagnosis of Kawasaki disease.

N-terminal pro-brain natriuretic peptide (NT-proBNP) has been studied as a diagnostic screening tool for Kawasaki disease (KD). However, brain natriuretic peptide (BNP) has been less studied while has less variability among age groups. We aimed to find out if BNP can be used as a diagnostic screening tool for KD in Korea. This was a retrospective cohort study performed in a single pediatric emergency department. Patients younger than 19 years of age who presented with fever and underwent BNP examination for suspected KD was included. The primary outcome was the diagnostic performance of BNP for KD, and the secondary outcome was the diagnostic performance of BNP for coronary artery aneurysm (CAA). We also derived a scoring system for predicting KD and CAA. Of the 778 patients who were finally included, 400 were not diagnosed with KD and 378 were diagnosed with KD. The odds ratio of BNP at the cutoff of 30 pg/mL for KD was 7.80 (95% CI, 5.67-10.73) in the univariate analysis and 3.62 (95% CI, 2.33-5.88) in the multivariable analysis. The odds ratio of BNP at the cutoff of 270 pg/mL for CAA was 3.67 (95% CI, 2.18-6.19) in the univariate analysis and 2.37 (95% CI, 1.16-8.74) in the multivariable analysis. The AUC of KD and CAA were 0.884 and 0.726, respectively, which was the highest AUCs among all variables. Additionally, we proposed a scoring system for KD and CAA. It is important to clinically suspect KD and CAA in children with high BNP levels.

Aloe-derived nanovesicles attenuate inflammation and enhance tight junction proteins for acute colitis treatment.

Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of the digestive tract that causes pain and weight loss and also increases the risk of colon cancer. Inspired by the benefits of plant-derived nanovesicles and aloe, we herein report aloe-derived nanovesicles, including aloe vera-derived nanovesicles (VNVs), aloe arborescens-derived nanovesicles (ANVs), and aloe saponaria-derived nanovesicles (SNVs) and evaluate their therapeutic potential and molecular mechanisms in a dextran sulfate sodium (DSS)-induced acute experimental colitis mouse model. Aloe-derived nanovesicles not only facilitate markedly reduced DSS-induced acute colonic inflammation, but also enable the restoration of tight junction (TJ) and adherent junction (AJ) proteins to prevent gut permeability in DSS-induced acute colonic injury. These therapeutic effects are ascribed to the anti-inflammatory and anti-oxidant effects of aloe-derived nanovesicles. Therefore, aloe-derived nanovesicles are a safe treatment option for IBD.

Predictors of Caregiver Satisfaction With Pediatric Laceration Repair in the Pediatric Emergency Department.

OBJECTIVES: The objective of this study was to define the care factors that are important to caregivers' satisfaction with pediatric laceration repair and the overall emergency department (ED) experience. METHODS: This was a cross-sectional observation study performed in an urban tertiary hospital. The caregivers of patients younger than 18 years who presented to the ED for laceration repair completed a survey. Demographic data were analyzed. Univariate and multivariate logistic regressions were used to determine the factors related to satisfaction with the laceration repair and the overall ED experience. RESULTS: Fifty-five caregivers were enrolled. Most of the children had facial lacerations (n = 44, 80%). The median length of ED stay was 181 minutes (interquartile range [IQR], 157-208 minutes). The children's median age was 41.8 months (IQR, 23-91 months); the caregivers' median age was 37 years (IQR, 35-41 years). Most lacerations were repaired by plastic surgeons (81.8%). In the multivariate regression analysis, preparation before the procedure, mid-income family, caring attitude of the nurse, cosmetic outcome, and measures to control the patient's anxiety were significantly related to the caregiver's satisfaction with laceration repair (P < 0.05), whereas preparation before the procedure and ED environment were significantly related to the caregiver's satisfaction with the overall ED experience (P < 0.05). CONCLUSIONS: Preparation before the procedure was significantly related to the caregiver's satisfaction with both pediatric laceration repair and the overall PED experience. The strongest predictors were cosmetic outcome for laceration repair and preparation for the procedure for the overall PED experience. Our findings suggest that improvements in various aspects will increase parent satisfaction.

Crystal structure of LRG1 and the functional significance of LRG1 glycan for LPHN2 activation.

The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1), primarily produced by hepatocytes and neutrophils, is a multifunctional protein that modulates various signaling cascades, mainly TGFß signaling. Serum LRG1 and neutrophil-derived LRG1 have different molecular weights due to differences in glycosylation, but the impact of the differential glycan composition in LRG1 on its cellular function is largely unknown. We previously reported that LRG1 can promote both angiogenic and neurotrophic processes under hyperglycemic conditions by interacting with LPHN2. Here, we determined the crystal structure of LRG1, identifying the horseshoe-like solenoid structure of LRG1 and its four N-glycosylation sites. In addition, our biochemical and cell-biological analyses found that the deglycosylation of LRG1, particularly the removal of glycans on N325, is critical for the high-affinity binding of LRG1 to LPHN2 and thus promotes LRG1/LPHN2-mediated angiogenic and neurotrophic processes in mouse tissue explants, even under normal glucose conditions. Moreover, the intracavernous administration of deglycosylated LRG1 in a diabetic mouse model ameliorated vascular and neurological abnormalities and restored erectile function. Collectively, these data indicate a novel role of LRG1 glycans as molecular switches that can tune the range of LRG1's cellular functions, particularly the LRG1/LPHN2 signaling axis.

Development of a screening platform to discover natural products active against SARS-CoV-2 infection using lung organoid models.

BACKGROUND: Natural products can serve as one of the alternatives, exhibiting high potential for the treatment and prevention of COVID-19, caused by SARS-CoV-2. Herein, we report a screening platform to test the antiviral efficacy of a natural product library against SARS-CoV-2 and verify their activity using lung organoids. METHODS: Since SARS-CoV-2 is classified as a risk group 3 pathogen, the drug screening assay must be performed in a biosafety level 3 (BSL-3) laboratory. To circumvent this limitation, pseudotyped viruses (PVs) have been developed as replacements for the live SARS-CoV-2. We developed PVs containing spikes from Delta and Omicron variants of SARS-CoV-2 and improved the infection in an angiotensin-converting enzyme 2 (ACE2)-dependent manner. Human induced pluripotent stem cells (hiPSCs) derived lung organoids were generated to test the SARS-CoV-2 therapeutic efficacy of natural products. RESULTS: Flavonoids from our natural product library had strong antiviral activity against the Delta- or Omicron-spike-containing PVs without affecting cell viability. We aimed to develop strategies to discover the dual function of either inhibiting infection at the beginning of the infection cycle or reducing spike stability following SARS-CoV-2 infection. When lung cells are already infected with the virus, the active flavonoids induced the degradation of the spike protein and exerted anti-inflammatory effects. Further experiments confirmed that the active flavonoids had strong antiviral activity in lung organoid models. CONCLUSION: This screening platform will open new paths by providing a promising standard system for discovering novel drug leads against SARS-CoV-2 and help develop promising candidates for clinical investigation as potential therapeutics for COVID-19.

Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice.

Plants-releasing exosome-like nanovesicles (PENs) contain miRNA, bioactive lipids, mRNAs, and proteins to exert antioxidant, anti-inflammatory, and regenerative activity. Substances extracted from yams have been reported to promote osteoblast growth in bone regeneration, which prevent weak and brittle bones in osteoporosis. Herein, we describe the beneficial effects of yam-derived exosome-like nanovesicles (YNVs) on promoting differentiation and mineralization of osteoblasts for bone regeneration in ovariectomized (OVX)-induced osteoporotic mice. YNVs were successfully isolated and characterized. YNVs stimulate the proliferation, differentiation, and mineralization of osteoblasts with increased bone differentiation markers (OPN, ALP, and COLI). Interestingly, YNVs do not contain saponins including diosgenin and dioscin known to mainly exert osteogenic activity of yams. Instead, the osteogenic activity of YNVs was revealed to be resulted from activation of the BMP-2/p-p38-dependent Runx2 pathway. As a result, YNVs promote longitudinal bone growth and mineral density of the tibia in the OVX-induced osteoporotic mice in vivo, and these results positively correlate the significant increases in osteoblast-related parameters. In addition, the orally administered YNVs were transported through the GI tract and absorbed through the small intestine. These results showed an excellent systemic biosafety determined by histological analysis and liver/kidney toxicity tests. Taken together, YNVs can serve as a safe and orally effective agent in the treatment of osteoporosis.