Search

BackgroundHypertension is one of the most important cardiovascular disease risk factors and affects >100 million American adults. Hypertension-related health inequities are abundant in Black communities as Black individuals are more likely to use the emergency department (ED) for chronic disease–related ambulatory care, which is strongly linked to lower blood pressure (BP) control, diminished awareness of hypertension, and adverse cardiovascular events. To reduce hypertension-related health disparities, we developed MI-BP, a culturally tailored multibehavior mobile health intervention that targeted behaviors of BP self-monitoring, physical activity, sodium intake, and medication adherence in Black individuals with uncontrolled hypertension recruited from ED and community-based settings. ObjectiveWe sought to determine the effect of MI-BP on BP as well as secondary outcomes of physical activity, sodium intake, medication adherence, and BP control compared to enhanced usual care control at 1-year follow-up. MethodsWe conducted a 1-year, 2-group randomized controlled trial of the MI-BP intervention compared to an enhanced usual care control group where participants aged 25 to 70 years received a BP cuff and hypertension-related educational materials. Participants were recruited from EDs and other community-based settings in Detroit, Michigan, where they were screened for initial eligibility and enrolled. Baseline data collection and randomization occurred approximately 2 and 4 weeks after enrollment to ensure that participants had uncontrolled hypertension and were willing to take part. Data collection visits occurred at 13, 26, 39, and 52 weeks. Outcomes of interest included BP (primary outcome) and physical activity, sodium intake, medication adherence, and BP control (secondary outcomes). ResultsWe obtained consent from and enrolled 869 participants in this study yet ultimately randomized 162 (18.6%) participants. At 1 year, compared to the baseline, both groups showed significant decreases in systolic BP (MI-BP group: 22.5 mm Hg decrease in average systolic BP and P

BackgroundEmergency departments (EDs) are complex and fast-paced clinical settings where a diagnosis is made in a time-, information-, and resource-constrained context. Thus, it is predisposed to suboptimal diagnostic outcomes, leading to errors and subsequent patient harm. Arriving at a timely and accurate diagnosis is an activity that occurs after an effective collaboration between the patient or caregiver and the clinical team within the ED. Interventions such as novel sociotechnical solutions are needed to mitigate errors and risks. ObjectiveThis study aims to identify challenges that frontline ED health care providers and patients face in the ED diagnostic process and involve them in co-designing technological interventions to enhance diagnostic excellence. MethodsWe will conduct separate sessions with ED health care providers and patients, respectively, to assess various design ideas and use a participatory design (PD) approach for technological interventions to improve ED diagnostic safety. In the sessions, various intervention ideas will be presented to participants through storyboards. Based on a preliminary interview study with ED patients and health care providers, we created intervention storyboards that illustrate different care contexts in which ED health care providers or patients experience challenges and show how each intervention would address the specific challenge. By facilitating participant group discussion, we will reveal the overlap between the needs of the design research team observed during fieldwork and the needs perceived by target users (ie, participants) in their own experience to gain their perspectives and assessment on each idea. After the group discussions, participants will rank the ideas and co-design to improve our interventions. Data sources will include audio and video recordings, design sketches, and ratings of intervention design ideas from PD sessions. The University of Michigan Institutional Review Board approved this study. This foundational work will help identify the needs and challenges of key stakeholders in the ED diagnostic process and develop initial design ideas, specifically focusing on sociotechnological ideas for patient-, health care provider–, and system-level interventions for improving patient safety in EDs. ResultsThe recruitment of participants for ED health care providers and patients is complete. We are currently preparing for PD sessions. The first results from design sessions with health care providers will be reported in fall 2024. ConclusionsThe study findings will provide unique insights for designing sociotechnological interventions to support ED diagnostic processes. By inviting frontline health care providers and patients into the design process, we anticipate obtaining unique insights into the ED diagnostic process and designing novel sociotechnical interventions to enhance patient safety. Based on this study’s collected data and intervention ideas, we will develop prototypes of multilevel interventions that can be tested and subsequently implemented for patients, health care providers, or hospitals as a system. International Registered Report Identifier (IRRID)DERR1-10.2196/55357

Safe and effective sedation depends on various factors, such as the choice of sedatives, sedation techniques used, experience of the sedation provider, degree of sedation-related education and training, equipment and healthcare worker availability, the patient’s underlying diseases, and the procedure being performed. The purpose of these evidence-based multidisciplinary clinical practice guidelines is to ensure the safety and efficacy of sedation, thereby contributing to patient safety and ultimately improving public health. These clinical practice guidelines comprise 15 key questions covering various topics related to the following: the sedation providers; medications and equipment available; appropriate patient selection; anesthesiologist referrals for high-risk patients; pre-sedation fasting; comparison of representative drugs used in adult and pediatric patients; respiratory system, cardiovascular system, and sedation depth monitoring during sedation; management of respiratory complications during pediatric sedation; and discharge criteria. The recommendations in these clinical practice guidelines were systematically developed to assist providers and patients in sedation-related decision making for diagnostic and therapeutic examinations or procedures. Depending on the characteristics of primary, secondary, and tertiary care institutions as well as the clinical needs and limitations, sedation providers at each medical institution may choose to apply the recommendations as they are, modify them appropriately, or reject them completely.

In recent years, there has been increasing interest in exploring the potential therapeutic advantages of Citrullus mucosospermus extracts (CME) for nonalcoholic steatohepatitis (NASH). In this study, we investigated the therapeutic effects of CME on NASH using a mice model. High-performance liquid chromatography (HPLC) was employed to identify cucurbitacin E and cucurbitacin E-2-O-glucoside from the CME. Although CME did not significantly alter the serum lipid levels in methionine- and choline-deficient (MCD) mice, it demonstrated a protective effect against MCD diet-induced liver damage. CME reduced histological markers, reduced alanine transaminase (ALT) and aspartame transaminase (AST) levels, and modulated key NASH-related genes, including C/EBPα, PPARγ, Fas, and aP2. In addition, CME was found to restore hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) activity, both crucial for fat catabolism, and reduced the levels of pro-inflammatory cytokines. Furthermore, CME demonstrated the potential to mitigate oxidative stress by maintaining or enhancing the activation and expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and superoxide dismutase (SOD), both pivotal players in antioxidant defense mechanisms. These findings underscore the promising therapeutic potential of CME in ameliorating liver damage, inflammation, and oxidative stress associated with NASH.

This study aimed to investigate the therapeutic potential of Citrullus mucosospermus extract (CME) in counteracting adipogenesis and its associated metabolic disturbances in murine models. In vitro experiments utilizing 3T3-L1 preadipocytes revealed that CME potently inhibited adipocyte differentiation, as evidenced by a dose-dependent reduction in lipid droplet formation. Remarkably, CME also attenuated glucose uptake and intracellular triglyceride accumulation in fully differentiated adipocytes, suggesting its ability to modulate metabolic pathways in mature adipose cells. Translating these findings to an in vivo setting, we evaluated the effects of CME in C57BL/6N mice fed a high-fat diet (HFD) for 10 weeks. CME administration, concomitantly with the HFD, resulted in a significant attenuation of body weight gain compared to the HFD control group. Furthermore, CME treatment led to substantial reductions in liver weight, total fat mass, and deposits of visceral and retroperitoneal adipose tissue, underscoring its targeted impact on adipose expansion. Histological analyses revealed the remarkable effects of CME on hepatic steatosis. While the HFD group exhibited severe lipid accumulation within liver lobules, CME dose-dependently mitigated this pathology, with the highest dose virtually abolishing hepatic fat deposition. An examination of adipose tissue revealed a progressive reduction in adipocyte hypertrophy upon CME treatment, culminating in a near-normalization of adipocyte morphology at the highest dose. Notably, CME exhibited potent anti-inflammatory properties, significantly attenuating the upregulation of pro-inflammatory cytokines’ mRNA levels (TNF-α, IL-1β and IL-6) in the livers of HFD-fed mice. This suggests a potential mechanism through which CME may exert protective effects against inflammation associated with obesity and fatty liver disease.

Systemic glucocorticoid treatment is highly recommended in critically ill coronavirus disease 2019 (COVID-19) patients. However, secondary fungal infections are of concern in such patients. Here, we describe the first case of COVID-19-associated invasive pulmonary aspergillosis (CAPA) and COVID-19-associated mucormycosis (CAM) coinfection in a COVID-19 positive immunocompetent patient in Korea. A 69-year-old man was admitted to our hospital with COVID-19 pneumonia. He had no underlying comorbidities and was not taking medications. He received remdesivir, dexamethasone, and antibiotic therapy under mechanical ventilation. Although his condition improved temporarily, multiple cavities were observed on chest computed tomography, and Aspergillus fumigatus was cultured from tracheal aspiration culture. He was diagnosed with probable CAPA and received voriconazole therapy. However, his condition was not significantly improved despite having received voriconazole therapy for 4 weeks. After release from COVID-19 quarantine, he underwent bronchoscopy examination and was then finally diagnosed with CAPA and CAM coinfection on bronchoscopic biopsy. Antifungal treatment was changed to liposomal amphotericin B. However, his progress deteriorated, and he died 4 months after admission. This case highlights that clinical suspicion and active checkups are required to diagnose secondary fungal infections in immunocompetent COVID-19 patients who receive concurrent glucocorticoid therapy.

Abstract While economic inequality continues to rise within countries, efforts to address it have been largely ineffective, particularly those involving behavioral approaches. It is often implied but not tested that choice patterns among low-income individuals may be a factor impeding behavioral interventions aimed at improving upward economic mobility. To test this, we assessed rates of ten cognitive biases across nearly 5000 participants from 27 countries. Our analyses were primarily focused on 1458 individuals that were either low-income adults or individuals who grew up in disadvantaged households but had above-average financial well-being as adults, known as positive deviants. Using discrete and complex models, we find evidence of no differences within or between groups or countries. We therefore conclude that choices impeded by cognitive biases alone cannot explain why some individuals do not experience upward economic mobility. Policies must combine both behavioral and structural interventions to improve financial well-being across populations.

Abstract In this study, an analysis method was established for the quantification of residues of halquinol and its metabolites in livestock and fishery products using liquid chromatography–tandem mass spectrometry (LC–MS/MS). We selected beef, pork (muscle and fat), chicken, egg, milk, flat fish, eel, and shrimp as target samples for validation of the method owing to them being typical livestock and fishery products. Validation of the developed analysis method was performed using liquid chromatography–tandem mass spectrometry (LC–MS/MS) at three concentration levels (0.5, 1, and 2 × the maximum residue limits) following the Codex Alimentarius (CODEX) guidelines (CAC/GL 71–2009). For all samples, correlation coefficients (R2) exceeded 0.99, recoveries ranged between 75.59 and 119.36%, and coefficients of variation (CV) ranged between 1.39 and 28.66%, thus satisfying CODEX guidelines. In addition, inter-laboratory validation was conducted, and the resulting recoveries and CVs satisfied the CODEX guidelines; LOQ was established as 10 μg kg–1 for pig muscle and 5 μg kg–1 for the other samples. Therefore, the analysis method developed in this study can accurately and precisely screen for and quantify halquinol and its metabolites in livestock and fishery products.

Abstract Energy drinks, often advertised as dietary supplements that enhance physical and mental performance, have gained increasing popularity among adolescents and athletes. Several studies on individual ingredients such as caffeine or taurine have reported either adverse or favorable influences on myogenic differentiation, a key process in muscle regeneration to repair microtears after an intense workout session. However, the impact of different energy drinks with various formulas on muscle differentiation has never been reported. This study aims to examine the in vitro effects of various energy drink brands on myogenic differentiation. Murine C2C12 myoblast cells were induced to differentiate into myotubes in the presence of one of eight energy drinks at varying dilutions. A dose-dependent inhibition of myotube formation was observed for all energy drinks, supported by reduced percentage of MHC-positive nuclei and fusion index. Moreover, expression of myogenic regulatory factor MyoG and differentiation marker MCK were also decreased. Furthermore, given the variation in formulas of different energy drinks, there were remarkable differences in the differentiation and fusion of myotubes between energy drinks. This is the first study to investigate the impact of various energy drinks on myogenic differentiation and our results suggest an inhibitory effect of energy drinks in muscle regeneration.

The thermal stability of the in-house-developed foot-and-mouth disease (FMD) type O and A viruses was evaluated, and the O Jincheon virus was found to exhibit the lowest thermal stability. To overcome this instability, we proposed a novel stabilizer, calcium chloride. The thermal stability of FMDVs increased up to a CaCl2 concentration of 10 mM, and it had a decreasing trend at >30 mM. The O Jincheon virus showed a significant decrease in the amount of antigen over time at 4 °C. In contrast, the samples treated with CaCl2 showed stable preservation of the virus without significant antigen loss. After the CaCl2-formulated vaccine was administered twice to pigs, the virus neutralization titer reached approximately 1:1000, suggesting that the vaccine could protect pigs against the FMDV challenge. In summary, the O Jincheon virus is difficult to utilize as a vaccine given its low stability during storage after antigen production. However, following its treatment with CaCl2, it can be easily utilized as a vaccine. This study evaluated CaCl2 as a novel stabilizer in FMD vaccines and may contribute to the development of stable vaccine formulations, especially for inherently unstable FMDV strains.

Since the foot-and-mouth disease (FMD) outbreak in South Korea in 2010–2011, vaccination policies utilizing inactivated FMD vaccines composed of types O and A have been implemented nationwide. However, because type Asia1 occurred in North Korea in 2007 and intermittently in neighboring countries, the risk of type Asia1 introduction cannot be ruled out. This study evaluated the antigen yield and viral inactivation kinetics of the recombinant Asia1 Shamir vaccine strain (Asia1 Shamir-R). When Asia1 Shamir-R was proliferated in shaking flasks (1 L), a 2 L bioreactor (1 L), and a wave bioreactor (25 L), the antigen yields were 7.5 μg/mL, 5.2 μg/mL, and 3.8 μg/mL, respectively. The optimal FMDV inactivation conditions were 2 mM BEI at 26 °C and 1.0 mM BEI at 37 °C. There was no antigen loss due to BEI treatment, and only a decrease in antigen levels was observed during storage. The sera from pigs immunized with antigen derived from a bioreactor exhibited a neutralizing antibody titer of approximately 1/1000 against Asia1 Shamir and Asia1/MOG/05 viruses; therefore, Asia1 Shamir-R is expected to provide sufficient protection against both viruses. If an FMD vaccine production facility is established, this Asia1 Shamir-R can be employed for domestic antigen banks in South Korea.

BackgroundMobile health (mHealth) interventions can deliver personalized behavioral support to users in daily contexts. These interventions have been increasingly adopted to support individuals who require low-cost and low-burden support. Prior research has demonstrated the feasibility and acceptability of an mHealth intervention app (CareQOL) designed for use with informal care partners. To further optimize the intervention delivery, we need to investigate how care partners, many of whom lack the time for self-care, react and act in response to different behavioral messages. ObjectiveThe goal of this study was to understand the factors that impact care partners’ decision-making and actions in response to different behavioral messages. Insights from this study will help optimize future tailored and personalized behavioral interventions. MethodsWe conducted semistructured interviews with participants who had recently completed a 3-month randomized controlled feasibility trial of the CareQOL mHealth intervention app. Of the 36 participants from the treatment group of the randomized controlled trial, 23 (64%) participated in these interviews. To prepare for each interview, the team first selected representative behavioral messages (eg, targeting different health dimensions) and presented them to participants during the interview to probe their influence on participants’ thoughts and actions. The time of delivery, self-reported perceptions of the day, and user ratings of a message were presented to the participants during the interviews to assist with recall. ResultsThe interview data showed that after receiving a message, participants took various actions in response to different messages. Participants performed suggested behaviors or adjusted them either immediately or in a delayed manner (eg, sometimes up to a month later). We identified 4 factors that shape the variations in user actions in response to different behavioral messages: uncertainties about the workload required to perform suggested behaviors, concerns about one’s ability to routinize suggested behaviors, in-the-moment willingness and ability to plan for suggested behaviors, and overall capability to engage with the intervention. ConclusionsOur study showed that care partners use mHealth behavioral messages differently regarding the immediacy of actions and the adaptation to suggested behaviors. Multiple factors influence people’s perceptions and decisions regarding when and how to take actions. Future systems should consider these factors to tailor behavioral support for individuals and design system features to support the delay or adaptation of the suggested behaviors. The findings also suggest extending the assessment of user adherence by considering the variations in user actions on behavioral support (ie, performing suggested or adjusted behaviors immediately or in a delayed manner). International Registered Report Identifier (IRRID)RR2-10.2196/32842

Objectives To compare the urine output and estimated glomerular filtration rate (eGFR) of patients postoperatively administered sugammadex or glycopyrrolate 7 days following kidney transplantation (KT). Methods We retrospectively enrolled 134 consecutive patients who underwent KT under general anesthesia. Their urine output and eGFR were recorded every 24 hours between postoperative day (POD) 1 and 7. We used regression analysis to evaluate the relationship between the reversal agent administered and the outcomes of the participants. Results The urine output and eGFR of the participants did not differ between the two groups. Multivariate analysis showed that body mass index (BMI) (odds ratio (OR) 1.21; 95% confidence interval (CI) 1.05–1.40), diabetes mellitus (OR 3.14; 95% CI 1.07–9.16), neurovascular disease (OR 7.00; 95% CI 1.61–30.42), and the duration of surgery (OR 1.01; 95% CI 1.00–1.01) were associated with lower urine output on POD 7. In addition, only BMI (OR 1.25; 95% CI 1.09–1.42) was associated with low eGFR on POD 7. Conclusions The urine output and eGFR of patients administered sugammadex or glycopyrrolate following KT did not differ 7 days later. Moreover, glycopyrrolate does not affect urine output or eGFR on POD 7, according to multivariate regression analysis.

This paper presents a simple and environmentally friendly method for synthesizing Tagetes erecta L. gold nanoparticles (TE-GNPs) using an aqueous extract of Tagetes erecta L. (TE). The TE extract serves as a reducing and stabilizing agent, and its antioxidant activity is evaluated using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The TE extract exhibits significant DPPH and ABTS radical scavenging activities, indicating its strong antioxidative properties attributed to various antioxidant compounds. TE-GNPs are successfully synthesized by incubating the TE extract with a chloroauric acid solution, resulting in a color change from light yellow to ruby red. UV–Vis spectroscopy confirms the synthesis of TE-GNPs, evidenced by a characteristic absorption peak at approximately 524 nm, corresponding to the nanoparticles' surface plasmon resonance. Physicochemical characterization reveals that TE-GNPs possess nanoscale dimensions (28.9 ± 2.3 nm), stability (zeta potential of −31.5 ± 28), and a crystalline nature (validated via X-ray diffraction; XRD). Functional groups responsible for biosynthesis and stabilization are identified through Fourier transform infrared spectroscopy (FT-IR) analysis. high-resolution transmission electron microscopy (HR-TEM) images demonstrate the morphology, size, and dispersion of TE-GNPs, while selected area electron diffraction (SAED) patterns confirm their crystalline structures. Additionally, high-angle annular dark field (HAADF) imaging and energy-dispersive X-ray spectroscopy (EDX) spectroscopy verify the distribution and presence of gold in the TE-GNPs, respectively. Cytotoxicity assays confirm the biocompatibility of TE-GNPs. Furthermore, their potential in mitigating high glucose-induced cell death and oxidative stress in retinal pigment epithelial (RPE) cells is evaluated. Treatment with TE-GNPs restores the proliferation rate of RPE cells and reduces the proportion of apoptotic cells under high glucose conditions. TE-GNPs also decrease the high glucose-induced production of intracellular and mitochondrial reactive oxygen species. Markers of cellular senescence, including SA-β-galactosidase activity and lysosomal dysfunction, are attenuated by the TE-GNPs. Moreover, the TE-GNPs effectively reduce lipid accumulation and peroxidation in RPE cells exposed to high levels of glucose. These findings highlight the successful green synthesis of TE-GNPs using an aqueous extract of TE and underscore their desirable properties and anti-senescence effects.

Background Clearance of the sugammadex-rocuronium complex is limited to renal excretion. There are restrictions on the use of sugammadex in patients with severe renal impairment. A paucity of data supports the clinical safety of sugammadex in patients with renal impairment. We analyzed mortality after using sugammadex in patients with end-stage renal disease to establish evidence of safety for sugammadex. Methods We retrospectively collected the medical records of 2,134 patients with end-stage renal disease who were dependent on hemodialysis and underwent surgery under general anesthesia between January 2018 and December 2019. Propensity score matching was used. The primary outcome was the 30-day mortality rate, and secondary outcomes were the 1-year mortality rate and causes of death. Results A total of 2,039 patients were included in the study. Sugammadex was administered as a reversal agent for rocuronium in 806 (39.5%) patients; the remaining 1,233 (60.5%) patients did not receive sugammadex. After matching, 1,594 patients were analyzed; 28 (3.5%) of the 797 patients administered sugammadex, and 28 (3.5%) of the 797 patients without sugammadex, died within 30 days after surgery (P > 0.99); 38 (4.8%) of the 797 patients administered sugammadex, and 45 (5.7%) of the 797 patients without sugammadex, died within 1 year after surgery (P = 0.499). No significant differences in the causes of 30-day mortality were observed between the two groups after matching (P = 0.860). Conclusions In this retrospective study, sugammadex did not increase the 30-day and 1-year mortality rate after surgery in end-stage renal disease patients.

BackgroundMost commercial foot-and-mouth disease (FMD) vaccines have various disadvantages, such as low antibody titers, short-lived effects, compromised host defense, and questionable safety.ObjectivesTo address these shortcomings, we present a novel FMD vaccine containing Dectin-1 agonist, β-D-glucan, as an immunomodulatory adjuvant. The proposed vaccine was developed to effectively coordinate innate and adaptive immunity for potent host defense against viral infection.MethodsWe demonstrated β-D-glucan mediated innate and adaptive immune responses in mice and pigs in vitro and in vivo. The expressions of pattern recognition receptors, cytokines, transcription factors, and co-stimulatory molecules were promoted via FMD vaccine containing β-D-glucan.Resultsβ-D-glucan elicited a robust cellular immune response and early, mid-, and long-term immunity. Moreover, it exhibited potent host defense by modulating host’s innate and adaptive immunity.ConclusionOur study provides a promising approach to overcoming the limitations of conventional FMD vaccines. Based on the proposed vaccine’s safety and efficacy, it represents a breakthrough among next-generation FMD vaccines.

Foot-and-mouth disease (FMD) is a highly contagious viral infection causing acute and severe vesicular lesions in cattle and pigs, which has prompted global vaccination policies. This study presents a technique for enhancing antigen yield in SAT1 BOT and SAT3 ZIM by treatment with calcium chloride (CaCl2). We tested changes in cell viability in BHK-21 suspension cells treated with varying concentrations of CaCl2. The optimal CaCl2 concentration was determined based on antigen yield. The timing of CaCl2 supplementation relative to FMD virus inoculation was tested. Finally, the optimal medium for antigen production was identified. We observed a concentration-dependent decrease in BHK-21 cell viability at >7.5 mM CaCl2. A CaCl2 concentration of 3 mM yielded the most antigens. CaCl2 supplementation relative to FMD virus infection was optimal 2 h before or with viral inoculation. CD-BHK 21 medium supplemented with CaCl2 was the most productive medium. Specifically, SAT1 BOT and SAT3 ZIM showed improved antigen production in CD-BHK 21 medium with 3 mM CaCl2, while Provero-1 and Cellvento BHK-200 media showed no significant enhancement. Overall, CaCl2 supplementation enhanced FMD antigen productivity. This study provides a useful framework for enhancing antigen production efficiently in the FMD vaccine industry.

South Korea has experienced outbreaks of foot-and-mouth disease (FMD) of serotypes O and A, leading to nationwide vaccination with a bivalent vaccine. Since the FMD virus (FMDV) Asia1 group-V genotype occurred in North Korea in 2007, an Asia1/MOG/05 vaccine strain belonging to the Asia1 group-V genotype was developed using a genetic recombination method (Asia1/MOG/05-R). This study aimed to evaluate the antigen productivity and viral inactivation kinetics of Asia1/MOG/05-R to assess its commercial viability. The antigen yield of Asia1/MOG/05-R produced in flasks and bioreactors was approximately 4.0 μg/mL. Binary ethylenimine (BEI) inactivation kinetics of Asia1/MOG/05-R showed that 2 mM and 1.0 mM BEI treatment at 26 °C and 37 °C, respectively, resulted in a virus titer −7 TCID50/mL within 24 h, meeting the inactivation kinetics criteria. During incubation at 26 °C and 37 °C, 10% antigen loss occurred, but not due to BEI treatment. When pigs were inoculated twice with the Asia1/MOG/05-R antigen, the virus neutralization titer increased to approximately 1:1000; therefore, it can sufficiently protect against Asia1/MOG/05-R and Asia1 Shamir viruses. The Asia1/MOG/05-R will be useful as a vaccine strain for domestic antigen banks.

All pigs in the Republic of Korea are given the foot-and-mouth disease virus (FMDV) vaccine intramuscularly (IM) as part of the country’s vaccination policy. However, the IM administration of the FMDV vaccine to pig results in residual vaccine components in the muscle and undesirable changes in muscle and soft tissues, causing economic losses in swine production. In this study, we evaluated whether intradermal (ID) vaccination could be proposed as an alternative to IM administration. ID vaccination (0.2 mL on each side of the neck muscle) and IM vaccination (2 mL on each side of the neck muscle) were performed twice, separated by 14 days, using a commercial FMD vaccine in specific-pathogen-free pigs. We observed growth performance, gross and microscopic lesions at the inoculation site, FMDV-specific antibodies, and neutralizing antibodies for 35 days after vaccination. Side effects on the skin grossly appeared following ID administration, but most were reduced within two weeks. All ID-vaccinated pigs showed inflammatory lesions limited to the dermis, but IM-vaccinated pigs had abnormal undesirable changes and pus in the muscle. ID-vaccinated pigs performed comparably to IM-vaccinated pigs in terms of growth, FMD virus-specific antibodies, protection capability against FMDV, and T-cell induction. This study demonstrated that the ID inoculation of the inactivated FMD vaccine induced immune responses comparable to an IM injection at 1/10 of the inoculation dose and that the inoculation lesion was limited to the dermis, effectively protecting against the formation of abnormal undesirable changes in muscle and soft tissues.

Bladder cancer, the most common malignancy of the urinary tract, has a poor overall survival rate when the tumor becomes muscle invasive. The discovery and evaluation of new alternative medications targeting high-grade muscle invasive bladder cancer (MIBC) are of tremendous importance in reducing bladder cancer mortality. Isorhapontigenin (ISO), a stilbene derivative from the Chinese herb Gnetum cleistostachyum, exhibits a strong anti-cancer effect on MIBCs. Here, we report the whole transcriptome profiling of ISO-treated human bladder cancer T24 cells. A total of 1047 differentially expressed genes (DEGs) were identified, including 596 downregulated and 451 upregulated genes. Functional annotation and pathway analysis revealed that ISO treatment induced massive changes in gene expression associated with cell movement, migration, invasion, metabolism, proliferation, and angiogenesis. Additionally, ISO treatment-activated genes involved in the inflammatory response but repressed genes involved in hypoxia signaling, glycolysis, the actin cytoskeleton, and the tumor microenvironment. In summary, our whole transcriptome analysis demonstrated a shift in metabolism and altered actin cytoskeleton in ISO-treated T24 cells, which subsequently contribute to tumor microenvironment remodeling that suppresses tumor growth and progression.

Background The number of patients with end-stage renal disease (ESRD) who are dependent on hemodialysis is increasing rapidly. As a result, more patients with ESRD need surgery. These patients have a significantly higher risk of postoperative death than those with normal kidney function. Therefore, this study analyzed the causes of postoperative mortality in ESRD patients undergoing surgery under general anesthesia and the risk factors for postoperative mortality. Methods This retrospective analysis examined the mortality of ESRD patients, 20 to 80 years old, undergoing surgery under general anesthesia. We excluded patients who underwent cardiac, cancer, or emergency surgery or organ transplantation from the analysis. The primary outcome was the cause of postoperative 30-day mortality in ESRD patients. We also assessed the mortality rate and risk factors. Results There were 2,459 eligible ESRD patients. When patients underwent multiple surgeries during the study period, only the last surgery was considered. In total, 167 patients died during the study period, including 65 within 30 days postoperatively. The cause of death was sepsis in 22 cases (33.8%) and a major cardiac event in 16 (24.6%). Atrial fibrillation, current angina, previous myocardial infarction, asthma, lower hemoglobin and albumin levels, and a larger intraoperative colloid volume were likely to increase mortality. Conclusions Our study suggests that immunological issues have a significant role in the death of ESRD patients after general anesthesia.

Seaweed extracts and their specific polysaccharides are widely known for their ability to act as reducing and capping agents during nanoparticle synthesis. Their application is highly favored in green synthesis methods, owing to their eco-friendliness, cost-effectiveness, and remarkable time and energy efficiency. In this study, fucoidan extracted from Undaria pinnatifida sporophyll (UPS) is introduced as a polysaccharide that effectively serves as a dual-function reducing and capping agent for the synthesis of gold nanoparticles (AuNPs). Results from various analyses indicate that AuNPs derived from UPS extract display a uniform spherical shape with an average size of 28.34 ± 1.15 nm and a zeta potential of −37.49 ± 2.13 mV, conclusively confirming the presence of Au. The FT-IR spectra distinctly revealed the characteristic fucoidan bands on the stabilized UPS-AuNPs surface. A 1H-NMR analysis provided additional confirmation by revealing the presence of specific fucoidan protons on the UPS-AuNPs surface. To comprehensively evaluate the impact of UPS extract, UPS-AuNPs, and fucoidan on the biological properties of adipocytes, a rigorous comparative analysis of lipid droplet formation and morphology was conducted. Our findings revealed that adipocytes treated with UPS extract, fucoidan, and UPS-AuNPs, in that order, exhibited a reduction in the total lipid droplet surface area, maximum Ferret diameter, and overall Nile red staining intensity when compared to mature white adipocytes. Furthermore, our analysis of the effects of UPS extracts, UPS-AuNPs, and fucoidan on the expression of key markers associated with white adipose tissue browning, such as UCP1, PGC1a, and PRDM16, demonstrated increased mRNA and protein expression levels in the following order: UPS-AuNPs > fucoidan > UPS extracts. Notably, the production of active mitochondria, which play a crucial role in enhancing energy expenditure in beige adipocytes, also increased in the following order: UPS-AuNPs > fucoidan > UPS extract. These findings underscore the pivotal role of UPS extract, fucoidan, and UPS-AuNPs in promoting adipocyte browning and subsequently enhancing energy expenditure.

Background We compared upper- and lower-body forced-air blankets in terms of their ability to prevent perioperative hypothermia, defined as a reduction in body temperature to < 36.0°C, during the perioperative period in patients undergoing spine surgery in the prone position. Methods In total, 120 patients scheduled for elective spine surgery under general anesthesia were divided into an upper-warming group (n = 60) and a lower-warming group (n = 60). After inducing anesthesia and preparing the patient for surgery, including prone positioning, the upper and lower bodies of the patients in the upper- and lower-warming groups, respectively, were warmed using a forced-air warmer with specified upper and lower blankets. Body temperature was measured using a tympanic membrane thermometer during the pre- and post-operative periods and using a nasopharyngeal temperature probe during the intraoperative period. Patients were evaluated in terms of shivering, thermal comfort, and satisfaction in the post-anesthesia care unit (PACU). Results The incidence of intraoperative and postoperative hypothermia was lower in the upper-warming group than in the lower-warming group ([55.2% vs. 75.9%, P = 0.019] and [21.4% vs. 49.1%, P = 0.002]). Perioperative body temperature was higher in the upper-warming group (P < 0.001). However, intraoperative blood loss, postoperative thermal comfort scale and shivering scores, patient satisfaction, and PACU duration were similar in the two groups. Conclusions The upper-body blanket was more effective than the lower-body blanket for preventing perioperative hypothermia in patients who underwent spine surgery in the prone position.

BackgroundHealth care and well-being are 2 main interconnected application areas of conversational agents (CAs). There is a significant increase in research, development, and commercial implementations in this area. In parallel to the increasing interest, new challenges in designing and evaluating CAs have emerged. ObjectiveThis study aims to identify key design, development, and evaluation challenges of CAs in health care and well-being research. The focus is on the very recent projects with their emerging challenges. MethodsA review study was conducted with 17 invited studies, most of which were presented at the ACM (Association for Computing Machinery) CHI 2020 conference workshop on CAs for health and well-being. Eligibility criteria required the studies to involve a CA applied to a health or well-being project (ongoing or recently finished). The participating studies were asked to report on their projects’ design and evaluation challenges. We used thematic analysis to review the studies. ResultsThe findings include a range of topics from primary care to caring for older adults to health coaching. We identified 4 major themes: (1) Domain Information and Integration, (2) User-System Interaction and Partnership, (3) Evaluation, and (4) Conversational Competence. ConclusionsCAs proved their worth during the pandemic as health screening tools, and are expected to stay to further support various health care domains, especially personal health care. Growth in investment in CAs also shows the value as a personal assistant. Our study shows that while some challenges are shared with other CA application areas, safety and privacy remain the major challenges in the health care and well-being domains. An increased level of collaboration across different institutions and entities may be a promising direction to address some of the major challenges that otherwise would be too complex to be addressed by the projects with their limited scope and budget.

BackgroundPropofol-based total intravenous anesthesia (TIVA) is considered a prophylactic approach to decrease postoperative nausea and vomiting (PONV). Despite general anesthesia commonly being performed in end-stage renal disease (ESRD) patients, PONV in ESRD patients has not been well-described. We investigated PONV in peripheral vascular surgery under general anesthesia in ESRD patients.MethodsTo compare PONV between propofol-based TIVA and anesthesia with volatile anesthetics, we collected retrospective data from patients who underwent peripheral vascular surgery under general anesthesia from July 2018 to April 2020. We performed univariable and multivariable analyses, including factors that could be associated with PONV and those previously shown to affect PONV.ResultA total of 1,699 peripheral vascular surgeries under general anesthesia in ESRD patients were eligible for analysis. Based on the multivariable analysis, TIVA (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.35–0.60; P

This study focuses on the green synthesis of silver and gold nanoparticles using the marine algae extract, Sargassum horneri, as well as the degradation of organic dyes using biosynthesized nanoparticles as catalysts. The phytochemicals of the brown algae Sargassum horneri acted as reducing and capping agents for nanoparticle synthesis. Ultraviolet–visible absorption spectroscopy, dynamic light scattering, high-resolution transmission electron microscopy, selected area electron diffraction, energy dispersive X-ray spectroscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy were used to characterize the biosynthesized nanoparticles. The green-synthesized SH-AgNPs and SH-AuNPs exhibited high catalytic activity for degradation of organic dyes, such as methylene blue, rhodamine B, and methyl orange. The reduction reactions of dyes are based on pseudo-first-order kinetics.

Recently, with the development of metal nanostructure synthesis technology, Au nanostructures (AuNPs) are synthesized using seaweed extract without using an organic solvent and applied to the pharmaceutical field. In this regard, in this study, AuNPs biosynthesis was mediated through extracts of two brown algae (Sargassum siliquastrum [SS] and Sargassum horneri [SH]) without the use of stabilizers or surfactants. In addition, we investigated the effects of SS-AuNPs (SS-functionalized AuNPs) and SH-AuNPs (SH-functionalized AuNPs) on adipogenesis in adipocytes and their underlying molecular mechanisms. A rapid and simplified synthesis of SS-AuNP and SH-AuP was achieved using aqueous extracts of SS and SH. The morphology, structure and composition of SS-AuNPs and SH-AuNPs were characterized by DLS, FTIR, UV–Vis spectroscopy, HR-TEM and EDS analysis. The stable monodisperse SS-AuNPs and SH-AuPs were synthesized with mean sizes of 17.47 ± 0.13 nm and 21.0 ± 2.74 and zeta potentials of −31.9 ± 0.75 and −34.57 ± 4.43, the biosynthetic AuNPs with the face-centered structure of SS-AuNPs and SH-AuPs had crystalline characteristics, and many functional groups that play an important role in the biological reduction present in the SS and SH extracts were adsorbed on the surfaces of the SS-AuNPs and SH-AuPs. This study was conducted to investigate the effect of SS-AuNPs and SH-AuPs on adipogenesis in adipocytes. SS-AuNPs and SH-AuPs reduced morphological changes and increased lipid accumulation by approximately 80% compared with that in mature adipocytes (MDI-induced). This result was accompanied by a reduction in the triglyceride content. SS-AuNPs and SH-AuPs suppressed lipid accumulation by downregulating C/EBPα, PPARγ, SREBP 1, FAS, and aP2 mRNA and protein expression. Furthermore, SS-AuNPs and SH-AuPs induced the mRNA and protein expression of UCP1, PRDM16, and PGC1α to increase mitochondrial biogenesis in mature adipocytes and effectively induced brown adipogenesis. SS-AuNPs and SH-AuPs have potent anti-adipogenic effects and can be used as potential therapeutic agents for obesity.

This study investigated the anti-obesity effects of Cucumis melo var. gaettongchamoe (CG) in mice fed a high-fat diet (HFD). The mice received CG water extract (CGWE) treatment for 8 weeks, and changes in body weight and serum lipid levels were analyzed. The HFD + vehicle group showed a significant increase in body weight compared to the control group, while the HFD + CGWE and HFD + positive (orlistat) groups exhibited reduced body weight. Lipid profile analysis revealed lower levels of total cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol in the HFD + CGWE group compared to the HFD + vehicle group. The HFD + vehicle group had increased abdominal fat weight and fat content, whereas both HFD + CGWE groups showed significant reductions in abdominal fat content and adipocyte size. Additionally, CGWE administration downregulated mRNA expression of key proteins involved in neutral lipid metabolism. CGWE also promoted hepatic lipolysis, reducing lipid droplet accumulation in hepatic tissue and altering neutral lipid metabolism protein expression. Furthermore, CGWE treatment reduced inflammatory mediators and suppressed the activation of the mitogen-activated protein kinase pathway in hepatic tissue. In conclusion, CGWE shows promise as a therapeutic intervention for obesity and associated metabolic dysregulation, including alterations in body weight, serum lipid profiles, adipose tissue accumulation, hepatic lipolysis, and the inflammatory response. CGWE may serve as a potential natural anti-obesity agent.

Foot-and-mouth disease (FMD) is a highly infectious disease affecting cloven-hoofed animals and causes significant economic losses to the livestock industry. The Type O PanAsia-2 (O PA-2) vaccine strain is protective against a wide range of serotype O FMD virus (FMDV) strains in East Asia, and A22 Iraq/24/64 (A22 IRQ) is the most widely used vaccine strain in FMD vaccine antigen banks. The aim of this study was to produce antigens from O PA-2 and A22 IRQ viruses using a 100 L bioreactor and evaluate the protective efficacy of varying antigen concentrations in pigs. More than 2 μg/mL of the antigen was recovered from the O PA-2 and A22 IRQ virus-infected supernatants. Further, inactivation of O PA-2 and A22 IRQ by binary ethyleneimine revealed that the viral titers decreased below 10−7 TCID50/mL within 13 h and 9 h, respectively. The O PA-2 and A22 IRQ vaccines, containing 10 μg and 5 μg of antigen, respectively, provided protection against homologous viruses in pigs. This is the first report demonstrating that the antigens obtained from the pilot-scale production of O PA-2 and A22 IRQ are viable candidate vaccines. These results will pave the way for industrial-scale FMD vaccine production in South Korea.

Foot-and-mouth disease (FMD) vaccines must be produced in a biosafety level 3 facility, so the FMD virus (FMDV) must be completely inactivated after amplification. The inactivation kinetics of FMDV during vaccine antigen production were assessed by evaluating whether the viral titer dropped below 10−7 TCID50/mL within 24 h of binary ethyleneimine (BEI) treatment. This study dealt with four FMD vaccine candidate strains for the efficacy of BEI treatment at different concentrations and temperatures to determine the optimal inactivation condition of each virus. Two domestic isolates, O/SKR/Boeun/2017 (O BE) and A/SKR/Yeoncheon/2017 (A YC), and two recombinant viruses, PAK/44/2008 (O PA-2) and A22/Iraq/24/64 (A22 IRQ), were investigated. The O BE and A22 IRQ required 2 mM BEI at 26 °C and 0.5 mM BEI at 37 °C for complete inactivation. The O PA-2 and A YC required 2 mM BEI at 26 °C and 1 mM BEI at 37 °C. Crucially, the yield of FMD virus particles (146S) in the viral infection supernatant was higher (>4.0 µg/mL) than those previously reported; additionally, there was little antigen loss, even after 24 h of treatment with 3 mM BEI. Overall, it is considered economical to produce FMD vaccines using these four kinds of viruses; therefore, these candidate strains will be prioritized for the manufacture of FMD vaccines in South Korea.

Background This study aimed to evaluate the efficacy of 10-min pre-warming in preventing inadvertent perioperative hypothermia, which is defined as a reduction in body temperature to less than 36.0℃ during the perioperative period in intraoperative warming patients. Methods In this prospective randomized study, 60 patients scheduled for elective surgery under general anesthesia lasting less than 120 min were divided into two groups: the 10-min pre-warming group (n = 30) and the control group (n = 30). Patients in the 10-min pre-warming group were pre-warmed for 10 min in the pre-anesthetic area using a forced-air warmer set at 47ºC. Intraoperatively, we warmed all patients with a forced-air warmer. Body temperature was measured using a tympanic membrane thermometer pre- or postoperatively and a nasopharyngeal temperature probe intraoperatively. Patients were evaluated on the shivering and thermal comfort scale in the pre-anesthetic area and post-anesthesia care unit. Results The incidences of intraoperative hypothermia and postoperative hypothermia were similar in both groups (10.7% vs. 28.6%, P = 0.177; 10.7% vs. 10.7%, P = 1.000 respectively). Body temperature was higher in the 10-min pre-warming group (P = 0.003). Thermal comfort during the pre-warming period was higher in the 10-min pre-warming group (P < 0.001). However, postoperative thermal comfort and shivering grades of both groups were similar. Conclusions Ten minutes of pre-warming has no additional effect on the prevention of inadvertent perioperative hypothermia in intraoperative warming patients.

Coagulation and transfusion management in patients undergoing liver transplantation is challenging. Proper perioperative monitoring of hemostasis is essential to predict the risk of bleeding during surgery, to detect potential causes of hemorrhage in time, and to guide hemostatic therapy. The value of conventional coagulation test is questionable in the acute perioperative setting due to their long turnaround time and the inability to adequately reflect the complex changes in hemostasis in patients with liver disease. Viscoelastic coagulation tests provide simultaneous measurement of multiple aspects of whole-blood coagulation including plasmatic coagulation and fibrinolytic factors and inhibitors that reflect most aspects of hemostasis. Coagulation initiation, mechanical clot stability, and fibrinolysis can be estimated immediately using point-of-care techniques. Therefore, viscoelastic coagulation tests including ROTEM & TEG would be useful to guide patient blood management strategy during liver transplantation.

Purpose To describe magnetic resonance imaging (MRI) findings in 10 cases of Toxocara canis myelitis and to analyze these findings to aid in the diagnosis of this condition. Materials and Methods From June 2015 to March 2018, we retrospectively analyzed the electronic medical records and MR images of patients who were diagnosed with Toxocara canis myelitis. The analysis of the MR images was based on a discussion between an experienced spinal radiologist and a radiology resident. Results This study classified MRI findings into the following two types. Type 1 was defined as central and diffuse T2 high signal intensity on the axial plane, which was observed in 50% of all cases. All lesions showed avid enhancement, mostly in the posterolateral or posterior region (4 cases, 80%). Type 2 was defined as wedge-shaped or focal T2 high signal intensity in the posterolateral or posterior region and corresponded to the remaining 50% of the cases. In this case, the extent of the lesion was relatively small and contrast enhancement was observed in only one case. Conclusion This study revealed that various imaging findings could be observed in cases of Toxocara canis myelitis, and the findings were classified into two types.

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease that affects cloven-hoofed animals and often causes enormous economic loss in the livestock industry. The capsid of FMD virus (FMDV) consists of four structural proteins. Initially, one copy each of the proteins VP0, VP3, and VP1 are folded together into a protomer, and five copies of the protomer compose a pentamer. Finally, 12 pentamers are assembled into an icosahedral capsid. At the maturation stage during RNA encapsidation, VP0 is cleaved into VP4 and VP2. The mechanism underlying VP0 maturation remains unclear. While monoclonal antibodies (mAbs) against VP2 have been developed in previous studies, a mAb specific to VP0 has not yet been reported. In this study, we generated VP0-specific mAbs by immunizing mice with peptides spanning the C-terminal amino acids of VP4 and N-terminal amino acids of VP2. We verified that these mAbs displayed specificity to VP0 with no reactivity to VP4 or VP2. Therefore, these mAbs could prove useful in identifying the role of VP0 in FMDV replication and elucidating the mechanism underlying VP0 cleavage into VP4 and VP2.

Loss of immunity is an important cause in the pathology of infectious disease. This study investigates the effect of Litsea japonica fruit extract (LJFE) as a potential functional food on immunity and hematopoietic function in immunosuppressed BALB/c mice. Immunity-stimulating activity was observed in mice supplemented with LJFE at low (25 mg/kg), medium (50 mg/kg), and high (100 mg/kg) dosage for seven days after administration of cyclophosphamide. LJFE treatment significantly improved spleen injury score (p < 0.001) and body weight (p < 0.02) by approximately two-fold with a high dosage of LJFE (100 mg/kg). Spleen-derived lymphocyte analysis demonstrated that the numbers of clusters of differentiation (CD)4+ and CD8+ T-cells were notably increased by approximately two-fold (p < 0.001) with a high dosage of LJFE (100 mg/kg). In mouse splenocytes differentiated into T- and B-lymphocytes, LJFE significantly induced proliferation up to approximately 90% of control for T- (p < 0.001) and B-lymphocytes (p < 0.01) with a high dosage of LJFE (100 mg/kg). Furthermore, LJFE significantly recovered the numbers of white blood cells, red blood cells, and platelets. Enzyme-linked immunosorbent assay revealed that serum levels of immune-related cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-2, and interferon (IFN)-γ, were notably Increased. In addition, serum levels of immunoglobulin (Ig) A, IgM, and IgG were restored by LJFE treatment. This study provides a reference to use L. japonica as a functional food ingredient to improve immunity and hematological function in humans.

The mechanism of white adipose tissue browning is not well understood; however, naturally occurring compounds are known to play a positive role. The effects of cucurbitacins B, E, and I on the browning of mature white adipocytes were investigated. First, the cell viability exhibited by cucurbitacins B, E, and I in pre- and mature adipocytes was verified. Cucurbitacins B, E, and I had no effect on cell viability in pre- and mature adipocytes at concentrations up to 300 nM. To investigate the characteristics of representative beige adipocytes, the formation and morphology of cucurbitacin B, E, and I lipid droplets were verified. The total lipid droplet surface area, maximum Feret diameter, and total Nile red staining intensity of cucurbitacin B-, E-, and I-treated adipocytes were lower than those of mature white adipocytes. Furthermore, treatment of white mature adipocytes with cucurbitacin B, E, and I led to the formation of several small lipid droplets that are readily available for energy expenditure. We evaluated the effect of cucurbitacins B, E, and I on the expression of representative browning markers UCP1, PGC1a, and PRDM16, which participate in the browning of white adipose tissue. Cucurbitacins B, E, and I increased the mRNA and protein expression levels of UCP1, PGC1a, and PRDM16 in a concentration-dependent manner. To promote energy consumption by beige adipocytes, active mitochondrial biogenesis is essential. Next, we investigated the effects of cucurbitacin B, E, and I on mitochondrial biogenesis in mature adipocytes. Mitochondrial mass increased when mature adipocytes were treated with cucurbitacin B, E, and I. The degree of cucurbitacin B-, E- and I-induced transformation of white adipocytes into beige adipocytes was in the order of Cu E > Cu B > Cu I. To verify the effect of phospholipase D2 on the browning of white adipocytes, CAY10594—a PLD2 pharmacological inhibitor, and a knockdown system were used. PLD2 inhibition and knockdown improved the expression levels of UCP1, PGC1a, and PRDM16. In addition, PLD2 inhibition and knockdown in mature white adipocytes promoted mitochondrial biosynthesis. The effect of PLD2 inhibition and knockdown on promoting browning of white adipocytes significantly increased when Cu B, Cu E, and Cu I were co-treated. These data indicate that mature white adipocytes’ beige properties were induced by cucurbitacins B, E, and I. These effects became more potent by the inhibition of PLD2. These findings provide a model for determining anti-obesity agents that induce browning and increase energy expenditure in mature white adipocytes.

Oxaliplatin is a platinum analog that can interfere with DNA replication and transcription. Continuous exposure to oxaliplatin results in chemoresistance; however, this mechanism is not well known. In this study, oxaliplatin-resistant (OR) colorectal cancer (CRC) cells of HCT116, HT29, SW480 and SW620 were established by gradually increasing the drug concentration to 2.5 μM. The inhibitory concentrations of cell growth by 50% (IC50) of oxaliplatin were 4.40–12.7-fold significantly higher in OR CRC cells as compared to their respective parental (PT) CRC cells. Phospho-Akt and phospho-mammalian target of rapamycin (mTOR) decreased in PT CRC cells but was overexpressed in OR CRC cells in response to oxaliplatin. In addition, an oxaliplatin-mediated decrease in phospho-AMP-activated protein kinase (AMPK) in PT CRC cells induced autophagy. Contrastingly, an increased phospho-AMPK in OR CRC cells was accompanied by a decrease in LC3B, further inducing the activity of glycolytic enzymes, such as glucose transporter 1 (GLUT1), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK1), to mediate cell survival. Inhibition of AMPK in OR CRC cells induced autophagy through inactivation of Akt/mTOR pathway and a decrease in GLUT1, PFKFB3, and PFK1. Collectively, targeting AMPK may provide solutions to overcome chemoresistance in OR CRC cells and restore chemosensitivity to anticancer drugs.

Identification of bacterial strains is critical for the theranostics of bacterial infections and the development of antibiotics. Many organic fluorescent probes have been developed to overcome the limitations of conventional detection methods. These probes can detect bacteria with “off-on” fluorescence change, which enables the real-time imaging and quantitative analysis of bacteria in vitro and in vivo. In this review, we outline recent advances in the development of fluorescence-based dyes capable of detecting bacteria. Detection strategies are described, including specific interactions with bacterial cell wall components, bacterial and intracellular enzyme reactions, and peptidoglycan synthesis reactions. These include theranostic probes that allow simultaneous bacterial detection and photodynamic antimicrobial effects. Some examples of other miscellaneous detections in bacteria have also been described. In addition, this review demonstrates the validation of these fluorescent probes using a variety of biological models such as gram-negative and -positive bacteria, antibiotic-resistant bacteria, infected cancer cells, tumor-bearing, and infected mice. Prospects for future research are outlined by presenting the importance of effective in vitro and in vivo detection of bacteria and development of antimicrobial agents.

Background The facilitator effects of steroids on neuromuscular transmission may cause resistance to neuromuscular blocking agents. Additionally, steroids may hinder sugammadex reversal of neuromuscular blockade, but these findings remain controversial. Therefore, we explored the effect of dexamethasone and hydrocortisone on rocuronium-induced neuromuscular blockade and their inhibitory effect on sugammadex. Methods We explored the effects of steroids, dexamethasone and hydrocortisone, in vitro using a phrenic nerve-hemidiaphragm rat model. In the first phase, an effective dose of rocuronium was calculated, and in the second phase, following sugammadex administration, the recovery of the train-of-four (TOF) ratio and T1 was evaluated for 30 minutes, and the recovery index was calculated in dexamethasone 0, 0.5, 5, and 50 μg/ml, or hydrocortisone 0, 1, 10, or 100 μg/ml. Results No significant effect of steroids on the effective dose of rocuronium was observed. The TOF ratios at 30 minutes after sugammadex administration were decreased significantly only at high experimental concentrations of steroids: dexamethasone 50 μg/ml and hydrocortisone 100 μg/ml (P < 0.001 and P = 0.042, respectively). There were no statistical significances in other concentrations. No differences were observed in T1. Recovery index was significantly different only in 100 μg/ml of hydrocortisone (P = 0.03). Conclusions Acute exposure to steroids did not resist the neuromuscular blockade caused by rocuronium. And inhibition of sugammadex reversal on rocuronium-induced neuromuscular blockade is unlikely at typical clinical doses of dexamethasone and also hydrocortisone. Conclusively, we can expect proper effects of rocuronium and sugammadex when dexamethasone or hydrocortisone is used during general anesthesia.

Background Phase-lag entropy (PLE) was recently described as a measurement of temporal pattern diversity in the phase relationship between two electroencephalographic signals from prefrontal and frontal montages. This study was performed to evaluate the performance of PLE for assessing the depth of sedation. Methods Thirty adult patients undergoing upper limb surgery with a brachial plexus block were administered propofol by target-controlled infusion. The depth of sedation was assessed using the Observer’s Assessment of Alertness/Sedation (OAA/S) scale. The effect-site concentration (Ce) of propofol was initially started at 0.5 μg/ml and was increased in increments of 0.2 μg/ml until an OAA/S score of 1 was reached. Three minutes after the target Ce was reached, the PLE, bispectral index (BIS), and level of sedation were assessed. Correlations between the OAA/S score and PLE or BIS were determined. The prediction probabilities (Pk) of PLE and BIS were also analyzed. Results The PLE values were closely correlated with the OAA/S scores (Spearman’s Rho = 0.755; P < 0.001) to an extent comparable with the correlation between the BIS and OAA/S score (Spearman’s Rho = 0.788; P < 0.001). The Pk values of PLE and BIS were 0.731 and 0.718, respectively. Conclusions PLE is a new and reliable consciousness monitoring system for assessing the depth of sedation induced by propofol, which is comparable with the BIS.

Background Considering the functional role of red blood cells (RBC) in maintaining oxygen supply to tissues, RBC transfusion can be a life-saving intervention in situations of severe bleeding or anemia. RBC transfusion is often inevitable to address intraoperative massive bleeding; it is a key component in safe perioperative patient management. Unlike general medical resources, packed RBCs (pRBCs) have limited availability because their supply relies entirely on voluntary donations. Additionally, excessive utilization of pRBCs may aggravate prognosis or increase the risk of developing infectious diseases. Appropriate perioperative RBC transfusion is, therefore, crucial for the management of patient safety and medical resource conservation. These concerns motivated us to develop the present clinical practice guideline for evidence-based efficient and safe perioperative RBC transfusion management considering the current clinical landscape. Methods This guideline was obtained after the revision and refinement of exemplary clinical practice guidelines developed in advanced countries. This was followed by rigorous evidence-based reassessment considering the healthcare environment of the country. Results This guideline covers all important aspects of perioperative RBC transfusion, such as preoperative anemia management, appropriate RBC storage period, and leukoreduction (removal of white blood cells using filters), reversal of perioperative bleeding tendency, strategies for perioperative RBC transfusion, appropriate blood management protocols, efforts to reduce blood transfusion requirements, and patient monitoring during a perioperative transfusion. Conclusions This guideline will aid decisions related to RBC transfusion in healthcare settings and minimize patient risk associated with unnecessary pRBC transfusion.

Foot-and-mouth disease (FMD) is an economically important and highly infectious viral disease, predominantly controlled by vaccination. The removal of non-structural proteins (NSPs) is very important in the process of FMD vaccine production, because vaccinated and naturally infected animals can be distinguished by the presence of NSP antibodies in the FMD serological surveillance. A previous study reported that 3AB protein, a representative of NSPs, was removed by chloroform treatment. Therefore, in this study, the causes of 3AB removal and factors affecting the effect of chloroform were investigated. As a result, the effectiveness of chloroform differed depending on the virus production medium and was eliminated by detergents. In addition, it was found that 3AB protein removal by chloroform is due to the transmembrane domain of the N-terminal region (59–76 amino acid domain). Further, industrial applicability was verified by applying the chloroform treatment process to scale-up FMD vaccine antigen production. A novel downstream process using ultrafiltration instead of polyethylene glycol precipitation for high-purity FMD vaccine antigen production was established. This result will contribute toward simplifying the conventional process of manufacturing FMD vaccine antigens and ultimately reducing the time and cost of vaccine production.

Here, Au nanostructure (AuNS) biosynthesis was mediated through ethanolic extract of Plocamium telfairiae (PT) without the use of stabilizers or surfactants. PT-functionalized AuNSs (PT-AuNSs) were analyzed using ultraviolet–visible spectroscopy, dynamic light scattering, high-resolution transmission electron microscopy, energy-dispersive spectroscopy, and Fourier-transform infrared spectroscopy. Stable monodisperse PT-AuNSs were synthesized, with a mean size of 15.36 ± 0.10 nm and zeta potential of −35.85 ± 1.36 mV. Moreover, biosynthetic AuNPs with a face-centered structure of PT-AuNS exhibited crystalline characteristics. In addition, many functional groups playing important roles in the biological reduction of PT extracts were adsorbed on the surface of PT-AuNSs. Furthermore, the effects of PT-AuNSs on adipogenesis in immature adipocytes were investigated. PT-AuNSs reduced morphological changes, lowered triglyceride content, and increased lipid accumulation by approximately 78.6% in immature adipocytes compared with the values in mature adipocytes (MDI-induced). PT-AuNS suppressed lipid accumulation by downregulating the transcript and protein expression of C/EBPα, PPARγ, SREBP 1, FAS, and aP2. Finally, PT-AuNS induced the transcript and protein expression of UCP1, PRDM16, and PGC1a, thereby increasing mitochondrial biogenesis in mature adipocytes and effectively inducing brown adipogenesis. In this study, the biosynthesized PT-AuNS was used as a potential therapeutic candidate because it conferred a potent anti-lipogenic effect. As a result, it can be used in various scientific fields such as medicine and the environment.

BackgroundTo determine whether the anesthetic method of propofol total intravenous anesthesia (TIVA) is associated with postoperative outcome in ESRD patients, we evaluated the incidence of postoperative major adverse cardiac events (MACE), comparing propofol TIVA versus anesthesia with volatile anesthesia in ESRD patients.MethodsRetrospectively, we identified cases with ESRD patients who underwent surgery under general anesthesia. Patients were divided into those who received only volatile anesthesia (volatile group) and those who received only propofol TIVA (TIVA group). The incidence of MACE and potential confounding variables were compared separately in a univariate logistic model and subsequently by multivariate logistic regression.ResultsAmong the 2576 cases in ESRD patients, 1374 were in the TIVA group and 1202 were in the volatile group. The multivariate analysis included 12 factors, including the anesthesia method, of which five factors were significant. Factors that were associated with a significantly lower MACE risk included preoperative chloride concentration (OR: 0.96; 95% CI, 0.92-0.99), baseline SBP (OR: 0.98; 95% CI, 0.98-0.99), and propofol TIVA (OR: 0.37; 95% CI, 0.22-0.60).ConclusionsWe inferred that the anesthetic method associated with the postoperative outcome in patients with ESRD.

It can be difficult for anesthesiologists to determine the optimal dose of propofol for end-stage kidney disease (ESKD) patients due to changes in drug disposition. The purpose of this study was to evaluate the potency of propofol for inducing loss of consciousness in ESKD patients. Patients with normal kidney function (Control group, n = 15), those with ESKD (ESKD group, n = 15), and those with ESKD undergoing cervical epidural anesthesia (ESKD-CEB group, n = 15) were administered propofol by target-controlled infusion (TCI) using the Schneider model. The effect-site concentration (Ce) of propofol started at 0.5 μg/ml and increased in increments of 0.5 μg/ml until the patient did not respond to verbal commands. The relationship between the probability (P) of loss of consciousness and the Ce of propofol was analyzed in each group using logistic regression. The Ce values of propofol at the time of loss of consciousness were 4.3 ± 0.9, 3.7 ± 0.9, and 3.3 ± 1.0 μg/ml for the Control, ESKD, and ESKD-CEB* groups, respectively (*significant difference vs. control, P < 0.05). The estimated Ce50 values for lost ability to respond to verbal command were 4.56, 3.75, and 3.21 μg/ml for the Control, ESKD, and ESKD-CEB groups, respectively. In conclusion, when inducing anesthesia in ESKD patients, we recommend using an initial dose similar to that of patients with normal kidney function, or rather starting with a lower dose.

Foot-and-mouth disease (FMD) causes substantial economic losses in the livestock industry. The protective immunizing component of the FMD virus (FMDV) is a ribonucleoprotein particle with a sedimentation coefficient of 146S. Size-exclusion high-performance liquid chromatography (SE-HPLC) was introduced to replace sucrose density gradient ultracentrifugation (SDG), which is the gold standard for the quantification of FMDV 146S particles. SE-HPLC showed a pattern similar to that of SDG; however, the two methods resulted in different quantities for the same amount of 146S particles. This study aimed to identify the reason for this disparity and adjust the difference between the two methods by employing a standard material. While SE-HPLC displayed all the virus particles in the peak fraction by SDS-PAGE and Western blotting, the virus particles were widely dispersed in multiple fractions, including peak fractions in the SDG. To adjust the difference between the two methods, a stable surrogate virus, bovine enterovirus, was devised to draw a standard curve, and the gap was reduced to

Purpose: Chronic irradiated wounds are characterized by a delayed and incomplete healing course. Currently, there are no therapies directed at the deficient or dysfunctional biology associated with cutaneous radiation injury. We have previously demonstrated that fibronectin is a key extracellular matrix glycoprotein known to be significantly downregulated in radiation-damaged skin. We further identified that an enzymatically crosslinked hydrogel is a suitable construct for incremental fibronectin release in vitro and in murine wound models. Our present objective was to investigate the design of this fibronectin hydrogel dressing for the treatment of irradiated wounds in the clinically relevant porcine irradiated wound model. Methods: We created a chronic irradiation skin injury model in female Yucatan minipigs. Two 1-month-old minipigs underwent irradiation of the right dorsolateral neck region for 5 consecutive days in 5.5 Gy fractionated doses for a total of 27.5 Gy. Following irradiation, the minipigs were allowed 6 weeks of recovery to enable chronic irradiation skin changes to develop. After recovery, nine 1 cm x 1 cm full-thickness wounds were created in the irradiated fields. After wound creation, 100 μl of fibronectin hydrogel was topically applied on experimental wounds and 100 μl of phosphate-buffered saline (PBS) hydrogel was applied on control wounds. Standardized wound photographs were taken at weekly time intervals to calculate the percentage of wound closure relative to original wound size. Tissues isolated from the wound areas were evaluated histologically for wound healing quality and analyzed for gene and protein levels of radiation injury mediators with quantitative RT-PCR and ELISA. Results: Wounds treated with fibronectin hydrogel demonstrated significantly faster wound closure and decreased scarring than wounds treated with PBS hydrogel. On postoperative day 21, the mean percentage of wound area relative to original wound size was significantly higher in the control wounds (21.3% ± 2.8%) than in the fibronectin-treated wounds (4.7 ± 1.0%). By the experimental endpoint on postoperative day 28, the mean percentage of control wound area was 6.8% ± 2.9% while all fibronectin-treated wounds were fully healed. Picrosirius red staining demonstrated that the fibronectin-treated wounds had decreased total scar area (9.9 ± 3.0 mm2) compared to control wounds (38.1 ± 3.6 mm2). In addition, fibronectin hydrogel treatment was associated with decreased levels of radiation-induced inflammatory mediators. RT-qPCR of samples from fibronectin-treated wounds had significantly lower mRNA levels of TGF-β1 (0.45 ± 0.09) compared to levels in control wounds (1 ± 0.13). Similarly, RT-qPCR data revealed that relative mRNA levels of SMAD3 were significantly lower in fibronectin-treated wounds (0.34 ± 0.11) than in control wounds (1 ± 0.43). Lastly, protein level correlation with ELISA identified significantly lower TGF-β1 concentrations in fibronectin-treated wounds (2682 + 515.83 pg/mL) compared to control wounds (5244.5 + 700.08 pg/mL). Conclusion: Hydrogel-facilitated delivery of fibronectin significantly improved the rate and quality of wound healing in a porcine chronic irradiation wound model. Thus, this novel mechanism of fibronectin supplementation demonstrates potential for treating these otherwise nonhealing wounds.