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Yun Seob Jung,1 Byung Hak Jin,2 Ju Eun Choi,2 Min Soo Park,2 Young-Woo Kim,3 Hyung Won Kang,4 Sunyoung Cho,5 Choon Ok Kim2 1Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea; 2Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea; 3School of Korean Medicine, Dongguk University, Gyeongju, Korea; 4College of Korean Medicine, Wonkwang University, Iksan, Korea; 5IntegroMediLab Co., Ltd, Seoul, KoreaCorrespondence: Choon Ok Kim, Department of Clinical Pharmacology, Severance Hospital, Yonsei University Health System, Seoul, Korea, Tel +82-2-2228-0455, Fax +82-2-2227-7890, Email delivery98@yuhs.acPurpose: Herbal medicines are occasionally used in combination with conventional antidepressants to mitigate various depression-associated symptoms. However, there is limited information on herb–antidepressant interactions. In this study, we investigated the pharmacokinetic (PK) effects of four herbal medicines (Gami-soyosan, Banhasasim-tang, Ojeok-san, and Bojungikgi-tang) on escitalopram, a commonly used antidepressant.Patients and Methods: In this open-label, fixed-sequence, three-period, crossover study, 18 participants were enrolled and divided into two groups. Each group received a 10 mg oral dose of escitalopram in period 1. Participants took escitalopram once daily and their assigned herbal medicines thrice a day for 7 d in periods 2 (group 1: Gami-soyosan, group 2: Ojeok-san) and 3 (group 1: Banhasasim-tang; group 2: Bojungikgi-tang). The primary endpoints were Cmax,ss and AUCtau,ss of escitalopram. Cmax,ss and AUCtau,ss in period 1 were obtained using nonparametric superposition from single-dose data. The PK endpoints were classified according to the CYP2C19 phenotype.Results: Of 18 participants, 16 completed the study. Systemic exposure to escitalopram resulted in a minor increase in the presence of each herbal medicine. The geometric mean ratios (GMRs, combination with herbal medicines/escitalopram monotherapy) and their 90% confidence intervals (CIs) for Cmax,ss and AUCtau,ss were as follows: Gamisoyosan– 1.1454 (0.9201, 1.4258) and 1.0749 (0.8084, 1.4291), Banhasasim-tang– 1.0470 (0.7779, 1.4092) and 1.0465 (0.7035, 1.5568), Ojeok-san– 1.1204 (0.8744, 1.4357) and 1.1267 (0.8466, 1.4996), and Bojungikgi-tang– 1.1264 (0.8594, 1.4762) and 1.1400 (0.8515, 1.5261), respectively. Furthermore, no significant differences in the GMRs of Cmax,ss and AUCtau,ss were observed across different CYP2C19 phenotypes in any of the groups.Conclusion: The co-administration of escitalopram with Gami-soyosan, Banhasasim-tang, Ojeok-san, or Bojungikgi-tang did not exert significant PK effects on escitalopram. These findings provide valuable insights into the safe use of herbal medicines along with escitalopram.Keywords: CYP2C19 phenotype, herb–drug interaction, antidepressant, geometric mean ratio

AIM OF THE STUDY: Gyeongshingangjeehwan (GGEx), which is a polyherbal drug composed of four medicinal plants, has traditionally been used as anti-obesity drug in Korean local clinics. Thus, we investigated the effects of GGEx on visceral adiposity and examined whether adipose peroxisome proliferator-activated receptor [alpha] (PPAR[alpha]) activation is involved in this process. MATERIALS AND METHODS: After Obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats and differentiated 3T3-L1 adipocytes were treated with GGEx, we studied the effects of GGEx on not only visceral white adipose tissue (WAT) mass and adipocyte size, but also the expression of adipocyte marker and PPAR[alpha] target genes. RESULTS: Administration of GGEx to obese rats for 8 weeks decreased visceral WAT weight by 30% and the size of adipocytes in mesenteric WAT by 31% without weight changes of other organs. Concomitantly, GGEx increased mRNA levels of PPAR[alpha] target genes responsible for fatty acid ß-oxidation in mesenteric WAT whereas decreased mRNA expression of adipocyte markers, such as PPAR[gamma], aP2 and leptin. Serological studies demonstrated that plasma levels of free fatty acids and triglycerides as well as insulin and glucose were decreased following GGEx treatment. Consistent with the in vivo data, GGEx increased PPAR[alpha] reporter gene activity and induced the mRNA expression of PPAR[alpha] target genes involved in mitochondrial fatty acid ß-oxidation in 3T3-L1 cells. GGEx also inhibited triglyceride accumulation in these cells. CONCLUSION: These results suggest that GGEx promotes the reductions in visceral fat mass and adipocyte size in obese animals, and that this event may be mediated by adipose PPAR[alpha] activation. [ABSTRACT FROM AUTHOR]

PURPOSE: The purpose of the present study was to evaluate the effect of an active physical therapy (PT) protocol after transoral vertical ramus osteotomy and to investigate the rehabilitation patterns of mandibular movement. MATERIALS AND METHODS: The study included 187 patients diagnosed with mandibular prognathism with or without facial asymmetry who had undergone bilateral transoral vertical ramus osteotomy from 2001 to 2009. The subjects were evaluated preoperatively and 1, 3, 6, 12, 18, and 24 months postoperatively in terms of the periods of PT and range of mandibular movement. The data were analyzed using 1-way analysis of variance (significance level, P < .05). RESULTS: Of the 187 patients, 108 (57.8%) did not receive repeat intermaxillary fixation (IMF) during the PT period, 58 (31.0%) received it once, 15 (8.0%) twice, and 6 patients more than 3 times. The average PT period for all was 10.9 days (range 5 to 45). The mean maximal mouth opening was 50.7 mm before surgery, decreasing to 33.9 mm at 1 month postoperatively. This was followed by an increase to 46.3 mm at 6 months postoperatively, with the maximal mouth opening thereafter showing 93.9% to 95.7% recovery compared with the preoperative state. CONCLUSIONS: About 88% of the patients with transoral vertical ramus osteotomy responded well to the reduced IMF duration and active PT protocols, receiving repeat IMF less than twice. It required about 6 months to recover 90% of the preoperative maximal mouth opening and 12 months to recover near preoperative levels statistically. The benefits of reduced IMF duration and the PT protocols seem to promote rehabilitation of the masticatory muscles and prevention of mandibular hypomobility. [ABSTRACT FROM AUTHOR]

Gyeongshingangjeehwan (GGEx), which comprises Liriope platyphylla F.T. Wang & T. Tang (Liliaceae), Platycodongrandiflorum A. DC. (Campanulaceae), Schisandrachinensis K. Koch (Magnoliaceae), and Ephedra sinica Stapf (Ephedraceae), has traditionally been used as an anti-obesity drug in Korean local clinics, although there is no evidence concerning the scientific analyses of its effects and mechanism(s) of action. Thus, we investigated the effects of GGEx on obesity, as well as the mechanism by which GGEx functions, in Otsuka Long-Evans Tokushima Fatty (OLETF) male rats. Compared with obese OLETF control rats, administration of GGEx for 8 weeks significantly decreased food intake and plasma leptin levels as well as body weight gain and abdominal fat in OLETF rats. GGEx treatment not only decreased circulating triglycerides, but also inhibited lipid accumulation in the liver. GGEx increased the hepatic mRNA levels of PPARalpha target genes responsible for fatty acid beta-oxidation. Consistent with the in vivo data, GGEx elevated PPARalpha reporter gene expression in NMu2Li liver cells. These results suggest that GGEx may effectively prevent obesity and hypertriglyceridemia in part through the inhibition of feeding and the activation of hepatic PPARalpha. [ABSTRACT FROM AUTHOR]

Purpose: While chronic exercise is known to have a positive influence on blood glucose regulation in older adults, the acute effect of maximal exercise on blood glucose regulation is unknown. In a cohort of masters athletes, it had been observed that younger athletes (YMA, ages 40-69) experienced postmaximal exercise glucose 'rebound' whereas older athletes (OMA, ages 70+) did not. The present study was conducted to reexamine this observation and to determine what role, if any, insulin may play. Methods: Ten YMA and 8 OMA matched for treadmill time and aerobic fitness were recruited as subjects. Blood samples were drawn at rest, immediately following maximal exercise on a treadmill, and at 2, 5, 10, 15, and 20 minutes into recovery. Plasma was analyzed for glucose, lactate, insulin, and c-peptide. Results: In this fitness-matched sample, both YMA and OMA experienced glucose rebound following maximal treadmill running, which was mirrored by an increase in plasma insulin. Significant time effects were observed for each variable, and significant between-group differences were noted for glucose at 15 min post (OMA = 8.4 +/- 1.9 mM vs. YMA = 6.4 +/- 1.6 mM) and resting insulin (YMA = 4.3 +/- 2.8 mIU * mL[-1] vs. OMA = 1.9 +/- 0.6 mIU mL[-1]) (p < 0.05). Conclusion: The most significant finding of the current study was the lack of age related differences in postmaximal exercise blood glucose concentration and/or its regulation. While aging may be associated with abnormal blood glucose regulation during recovery from maximal exercise, this effect seems to be blunted by chronic training. From a clinical perspective, this could be related to improved postexercise recovery and could provide a mechanism for the maintenance of physical function with advancing age. [ABSTRACT FROM AUTHOR]

N-Nitrosamines (NAs) pose a threat to food safety due to their carcinogenic and mutagenic properties. In this study, we developed and validated a QuEChERS-based LC-MS/MS method for the simultaneous analysis of 11 NAs in 74 processed fish meat, processed meat, and salted fish products. Sample preparation was optimized by screening two versions of QuEChERS buffer, four extraction methods, and eight purification methods. The optimal analytical approach was validated for three product categories in terms of linearity, matrix effects, accuracy, and precision. Satisfactory precision and accuracy were demonstrated, with relative recoveries of 70-120% for the 11 NAs. The limits of detection for fish meat, processed meat, and salted fish products were 0.12-7.50, 0.12-4.14, and 0.10-7.81 ng·g -1 , respectively. Among the 11 NAs, nine were detected in all 74 samples. This methodology could be applied to monitor NA levels to ensure the safety and quality of food products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aim: Tegoprazan, a potassium-competitive acid blocker, can be used as a substitute for proton pump inhibitors in Helicobacter pylori eradication therapy; some studies have reported improved efficacy. In Korea, where clarithromycin resistance rates are high, we aimed to compare the efficacies of tegoprazan-based concomitant and bismuth quadruple therapies., Methods: We retrospectively analyzed data from patients with H. pylori infection who received either 10-day tegoprazan-based concomitant therapy or 14-day tegoprazan-based bismuth quadruple therapy as first-line treatment. The primary outcome was H. pylori eradication rate, with secondary outcomes including adverse events and insufficient medication rates., Results: Among the 1082 patients included in the study, 620 and 462 were treated with tegoprazan-based concomitant and bismuth quadruple therapies, respectively. Intention-to-treat analysis demonstrated no difference in eradication rates between the tegoprazan-based concomitant and bismuth quadruple therapy groups (74.7% [95% confidence interval-CI, 71.1-78.0%] vs 74.7% [95% CI, 70.6-78.5%], P = 0.999). Per-protocol analysis also showed similar eradication rates between the two groups (88.0% [95% CI, 85.0-90.6%] vs 89.7% [95% CI, 86.3-92.5%], P = 0.424). The overall adverse event rates (49.6% vs 39.2%, P = 0.001) and insufficient medication rates (4.8% vs 2.4%, P = 0.036) were higher in the bismuth quadruple therapy group than in the concomitant therapy group., Conclusions: The eradication rates of tegoprazan-based 10-day concomitant therapy and 14-day bismuth quadruple therapy were comparable. However, because of its shorter treatment duration, better medical adherence, and lower incidence of adverse events, tegoprazan-based concomitant therapy may be preferable in regions with high rates of clarithromycin and metronidazole resistance., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Inside living organisms, proteins are self-assembled into diverse 3D structures optimized for specific functions. This structure-function relationship can be exploited to synthesize functional materials through biotemplating and depositing functional materials onto protein structures. However, conventional biotemplating faces limitations due to the predominantly intracellular existence of proteins and associated challenges in achieving tunability while preserving functionality. In this study, Conversion to Advanced Materials via labeled Biostructures (CamBio), an integrated biotemplating platform that involves labeling target protein structures with antibodies followed by the growth of functional materials, ensuring outstanding nanostructure tunability is proposed. Protein-derived plasmonic nanostructures created by CamBio can serve as precise quantitative tools for assessing target species is demonstrated. The assessment is achieved through highly tunable and efficient surface-enhanced Raman spectroscopy (SERS). CamBio enables the formation of dense nanogap hot spots among metal nanoparticles, templated by diverse fibrous proteins comprising densely repeated monomers. Furthermore, iterative antibody labeling strategies to adjust the antibody density surrounding targets, amplifying the number of nanogaps and consequently improving SERS performance are employed. Finally, cell-patterned substrates and whole meat sections as SERS substrates, confirming their easily accessible, cost-effective, scalable preparation capabilities and dimensional tunability are incorporated., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

To investigate air pollution's effect in the form of PM 2.5 (particulate matter measuring less than 2.5 microns) on head and neck aerodigestive cancer incidence, an epidemiological cohort analysis was performed using data from the Surveillance Epidemiology and End Results national cancer database from the years 2002-2012. The relationship between US county mean PM 2.5 levels and head and neck cancer (HNC) incidence rates were examined using a linear mixed model. Lagged effect of the pollutant's effect on HNC incidence was analyzed. Our results showed a significant association between the incidence of HNC and certain subtypes with PM 2.5 exposure after controlling for demographic characteristics, smoking and alcohol use. We observed the highest association at a 5-year lag period (β = 0.24, p value < 0.001). We observed significant associations at no lag (β = 0.16, p value = 0.02) and up to a 20-year lag period (β = 0.15, p value < 0.001). PM 2.5 exposure is associated with an increased incidence of HNC, with the strongest association at a 5-year lag period. To better understand the relationships between exposure and cancer pathogenesis, further subgroup analysis is needed., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: This study aimed to analyze the factors affecting the occurrence of peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ) in patients using anti-resorptive drugs (ARDs) on different implant position, inclinations, and types of prosthesis., Methods: The data of 75 patients with bone necrosis that progressed around the implant between 2018 and 2022 were retrospectively examined to identify the factors influencing PI-MRONJ. Data, including patient demographics (age, sex, smoking status, concomitant disease, time of ARD therapy, dose of ARDs, and parafunctional habits) and implant-specific information (type of prosthesis, angle of insertion), were extracted from medical and dental records., Results: Tilted implants with an angle ≥ 5.1° relative to the occlusal plane of the prosthesis had a stronger association with PI-MRONJ in comparison to non-tilted implants (inclination was < 5°). Additionally, the boundary of the area of osteonecrosis around the fixture was larger for the splinted implant-supported crowns than for the single implant supported crowns)., Conclusion: In patients taking anti-resorptive medications the inclination of the implant was associated with the occurrence of PI-MRONJ. Further studies are required to confirm the clinical findings., (© 2024 The Author(s). Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.)

Key Points: Decreased overall dietary consumption of micronutrients may be linked to an increased risk of olfactory dysfunction (OD) including subjective report of OD, subjective report of phantosmia, and objective OD. Interactions were identified between these micronutrients, suggesting that outcomes may vary depending on the mixture of micronutrients taken., (© 2024 ARS‐AAOA, LLC.)

Purpose: High-dose denosumab (Xgeva®) is increasingly used for treating bone metastasis and various malignant diseases but carries the risk of medication-related osteonecrosis of the jaw (MRONJ). This study aimed to evaluate the incidence, risk factors, and clinical outcomes of MRONJ in patients treated with high-dose denosumab., Methods: A retrospective review was performed on 1278 patients who received high-dose denosumab at Severance Hospital, Seoul, South Korea, from September 2014 to February 2023. Data on the incidence of MRONJ, patient demographics, primary diseases, and treatment outcomes were analyzed., Results: Among the 1278 patients (average age 64.72 years; 728 males and 550 females) treated, 34 developed MRONJ, with a 2.66% incidence rate. The average age of those with MRONJ was 68.32 years, and they received more Xgeva® injections on average (13.62) compared to the overall cohort. Factors such as age and the frequency of injections were significantly associated with the risk of MRONJ. Notably, the incidence of MRONJ did not significantly differ between those who underwent oral surgery and those with spontaneous MRONJ, especially if oral surgery occurred within 1 month of injection. Surgical interventions have shown higher recovery rates in advanced MRONJ stages., Conclusion: This study confirmed a significant MRONJ incidence of 2.66% among high-dose denosumab recipients, highlighting the importance of careful patient selection, monitoring, and education, particularly in older and long-term treatment patients, to mitigate the risk of MRONJ., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

During recovery from septic shock, circulating mitochondrial N-formyl peptides predispose to secondary infection by occupying formyl peptide receptor 1 on the neutrophil (polymorphonuclear leukocyte) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mitochondrial N-formyl peptides in clinical settings. Thus, we studied how to remove mitochondrial N-formyl peptides from septic-shock plasma and whether such removal could preserve cell-surface formyl peptide receptor 1 and restore sepsis-induced polymorphonuclear leukocyte dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mitochondrial N-formyl peptide removal rescued polymorphonuclear leukocyte formyl peptide receptor 1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mitochondrial N-formyl peptide exposure. However, polymorphonuclear leukocyte functional recovery occurred in a stepwise fashion over 30 to 90 min. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model, systems using blood samples obtained from patients with septic shock, antimitochondrial N-formyl peptide antibodies alone failed to eliminate mitochondrial N-formyl peptides from septic-shock plasma or inhibit mitochondrial N-formyl peptide activity. We therefore created a beads-based antimitochondrial N-formyl peptide antibody cocktail by combining protein A/sepharose with antibodies specific for the most potent human mitochondrial N-formyl peptide chemoattractants. The beads-based antimitochondrial N-formyl peptide antibody cocktail treatment successfully removed those active mitochondrial N-formyl peptides from septic-shock plasma. Furthermore, the beads-based antimitochondrial N-formyl peptide antibody cocktail treatment significantly restored chemotactic and bactericidal dysfunction of polymorphonuclear leukocytes obtained from patients with septic shock who developed secondary infections. By clearing circulating mitochondrial N-formyl peptides, the immobilized antimitochondrial N-formyl peptide antibody therapy prevented mitochondrial N-formyl peptide interactions with surface formyl peptide receptor 1, thereby restoring [Ca2+]i-dependent polymorphonuclear leukocyte antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock., Competing Interests: Conflict of interest statement. W.Y.K., Y.S.J., G.J.S., S.H.K., A.L., J.Y.K., H.Y.K., H.P., T.K., and K.S.K. are inventors on a patent application submitted by Seoul National University that covers “Blood perfusion device to reduce secondary infection in hospital”. The authors have declared no additional conflict of interest exists., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for Leukocyte Biology.)

Background/aims: Few real-world studies explored factors associated with latent tuberculosis infection (LTBI) treatment-related adverse drug reactions (ADRs). This study evaluate ADRs that lead to the discontinuation of LTBI treatment and identify the associated factors, including age groups and drug regimens., Methods: Using the Korean national tuberculosis registry and HHC investigation database linked to the National Health Insurance Service claims database, we examined treatment discontinuation due to ADRs among HHCs on LTBI treatment from January 2015 to December 2018. Multivariable logistic regression analysis was conducted to examine factors associated with ADRs, including demographics, LTBI treatment, comorbidities, and steroid use., Results: Among 11,913 participants initiated LTBI treatment, 633 participants (5.3%) discontinued treatment due to ADRs. The primary contributors to discontinuation were adverse skin reactions (2.0%) and abnormal liver function (1.9%). Risk associated with ADRs and abnormal liver function showed age-related increase, except for the age group 66-75 (adjusted odds ratio [AOR] 3.82, 95% confidence interval [CI] 2.31-6.31) which reported lower OR to that of age group 36-65 (AOR 4.38, 95% CI 3.09-6.21). Three months isoniazid/rifampin and 4 months rifampin exhibited a lower odds of ADRs and abnormal liver function when compared to 6-9 months isoniazid., Conclusion: We discovered the real-world prevalence of LTBI treatment discontinuation due to ADRs among HHCs. Our findings suggest a notably increased odds of ADRs resulting in discontinuation with age of 76 years or above, emphasizing careful attention when prescribing LTBI treatment in this population. Further studies are warranted to validate these results.

Senoinflammation is characterized by an unresolved low-grade inflammatory process that affects multiple organs and systemic functions. This review begins with a brief overview of the fundamental concepts and frameworks of senoinflammation. It is widely involved in the aging of various organs and ultimately leads to progressive systemic degeneration. Senoinflammation underlying age-related inflammation, is causally related to metabolic dysregulation and the formation of senescence-associated secretory phenotype (SASP) during aging and age-related diseases. This review discusses the biochemical evidence and molecular biology data supporting the concept of senoinflammation and its regulatory processes, highlighting the anti-aging and anti-inflammatory effects of calorie restriction (CR). Experimental data from CR studies demonstrated effective suppression of various pro-inflammatory cytokines and chemokines, lipid accumulation, and SASP during aging. In conclusion, senoinflammation represents the basic mechanism that creates a microenvironment conducive to aging and age-related diseases. Furthermore, it serves as a potential therapeutic target for mitigating aging and age-related diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The genus Wikstroemia has been extensively utilized in traditional Chinese medicine (TCM) for the management of conditions such as coughs, edema, arthritis, and bronchitis. Studies have indicated that the crude extracts of Wikstroemia exhibit anti-inflammatory, anti-allergy, anti-aging, skin psoriasis, anti-cancer, and antiviral properties. In addition, these extracts are known to contain bioactive substances, including flavonoids, coumarins, and lignans. However, few studies have investigated the anti-inflammatory or anti-allergic activities of Wikstroemia trichotoma (Thunb.) Makino against atopic dermatitis (AD)., Aim of the Study: The study aimed to explore the potential of a 95% ethanol extract of W. trichotoma (WTE) on the dysfunction of skin barrier and immune system, which are primary symptoms of AD, in 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice and phorbol 12-myristate 13-acetate (PMA)/ionomycin or immunoglobulin E (IgE) + 2,4-dinitrophenylated bovine serum albumin (DNP-BSA) stimulated rat basophilic leukemia cell line (RBL-2H3). Furthermore, we sought to identify the chemical contents of WTE using high-performance liquid chromatography equipped with a photodiode array detector (HPLC-PDA)., Materials and Methods: An in vitro study was conducted using RBL-2H3 cells stimulated with PMA/ionomycin or IgE + DNP-BSA to assess the inhibitory effects of WTE on mast cell degranulation and interleukin-4 (IL-4) mRNA expression levels. For the in vivo study, AD was induced in SKH-1 hairless mice by applying 1% DNCB to the dorsal skin daily for 7 days. Subsequently, 0.1% DNCB solution was applied on alternate days, and mice were orally administered WTE (at 30 or 100 mg/kg/day) dissolved in 0.5% carboxymethyl cellulose (CMC) daily for 2 weeks. Transepidermal water loss (TEWL), skin hydration, skin pH, and total serum IgE levels were measured., Results: In DNCB-stimulated SKH-1 hairless mice, WTE administration significantly improved AD symptoms and ameliorated dorsal skin inflammation. Oral administration of WTE led to a significant decrease in skin thickness, infiltration of mast cells, and level of total serum IgE, thus restoring skin barrier function in the DNCB-induced skin lesions. In addition, WTE inhibited β-hexosaminidase release and reduced IL-4 mRNA levels in RBL-2H3 cells. Chemical profile analysis of WTE confirmed the presence of three phenolic compounds, viz. chlorogenic acid, miconioside B, and matteucinol-7-O-β-apiofuranosyl (1 → 6)-β-glucopyranoside., Conclusions: WTE ameliorates AD symptoms by modulating in the skin barrier and immune system dysfunction. This suggests that W. trichotoma extract may offer therapeutic benefits for managing AD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: This study was conducted to assess the cost-effectiveness of prophylactic use of ramosetron compared to no antiemetic medications for the prevention of postoperative nausea and vomiting (PONV) from the healthcare payer and societal perspectives in South Korea., Method: A decision analytic model was constructed to assess the cost-effectiveness of prophylactic ramosetron use versus no antiemetic therapy at 24-hour and 48-hour periods post-surgery over a 5-day duration. The model was populated using costs and utility parameters from published studies as well as from surveys of an expert panel of physicians using structured questionnaires. The cost parameters included the costs of drugs, treatment, patient time, productivity loss, and transportation. Effectiveness was measured using quality adjusted life years (QALYs). The study outcome was the incremental cost-effectiveness ratio (ICER). The parameter uncertainties were addressed using deterministic and probabilistic scenario analyses., Results: The base-case analysis showed that, on average, patients treated with prophylactic ramosetron had lower costs from both the healthcare payer (US$16.88 vs US$17.33) and societal (US$16.89 vs US$18.72) perspectives and higher QALYs (0.0121 vs 0.0114) over the 5-day study duration compared to patients without any antiemetic medications. Deterministic and probabilistic sensitivity analyses were conducted to examine the robustness of results for the parameters included in the model. The acceptability curve probability showed that treating patients with ramosetron compared to no antiemetic medications was more than 99% cost-effective at a willingness-to pay threshold of US$5,000/QALY from both payer and societal perspectives., Conclusion: The results demonstrated that prophylactic use of ramosetron compared to no antiemetic therapy is highly cost-effective to prevent PONV for patients undergoing surgery from both healthcare payer and societal perspectives. The cost effectiveness is the result of the decrease in the incidence of PONV and the direct treatment costs of severe PONV with improved patient quality of life., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Suh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Insomnia is one of the most common sleep disorders, affecting 10-15% of the global population. Because classical remedies used to treat insomnia have various side effects, new therapeutics for insomnia are attracting attention. In the present study, we found that N 2 -Ethyl-N 4 -(furan-2-ylmethyl) quinazoline-2,4-diamine (AR-001) has adenosine A 1 receptor agonistic activity and exhibits hypnotic efficacy by decreasing sleep onset latency and increasing total sleep time in a pentobarbital-induced sleep model. This hypnotic effect of AR-001 was significantly inhibited by the adenosine A 1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). As a result of immunohistochemistry, AR-001 was shown to increase neural activity in the sleep-promoting region, ventrolateral preoptic nucleus (VLPO), and decrease neural activity in the wake-promoting region, basal forebrain (BF), and lateral hypothalamus (LH), and that these effects of AR-001 were significantly inhibited by DPCPX treatment. In addition, AR-001 increased adenosine A 1 receptor mRNA levels in the hypothalamus. In conclusion, this study suggests that AR-001 has a hypnotic effect, at least partially, through adenosine A 1 receptor and may have therapeutic potential for insomnia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yi-Sook Jung reports financial support was provided by GRRC program of Gyeonggi province (GRRCAjou2023-B01). Hye Jin Jee reports was provided by Korea Initiative for fostering University of Research and Innovation Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. NRF2021M3H1A104892211). Yi-Sook Jung reports financial support was provided by Ministry of Food and Drug Safety, Republic of Korea (21153MFDS602). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

One Health is an integrative approach that emphasizes the interconnectedness of human, animal, and environmental health, advocating for collaborative, multidisciplinary efforts to address health challenges, particularly amid globalization and emerging threats. This paper examines the integration of One Health principles into global health education, highlighting the importance of interdisciplinary collaboration and innovative pedagogical approaches. It evaluates various teaching methods, including problem-based learning (PBL), team-based learning (TBL), simulation-based education (SBE), case-based learning (CBL), interdisciplinary workshops and seminars (IWS), and service-learning (SL), analyzing their strengths and weaknesses in fostering interdisciplinary understanding and practical application of One Health concepts. While these methods enhance learning by promoting critical thinking, collaboration, and real-world application, they also face challenges such as resource constraints, variability in group dynamics, and the complexity of assessing long-term learning outcomes. The paper also discusses the role of global partnerships, such as the Global One Health Research Partnership (GOHRP), in advancing One Health education through collaborative research and educational initiatives. Addressing challenges in curriculum integration and interdisciplinary collaboration is crucial for the effective implementation of One Health education, ensuring that future health professionals are equipped to tackle complex global health challenges., Competing Interests: Chang Cai is the associate editor and Michael Brouwer is the editorial board member of Science in One Health. The authors have no other competing interest to disclose., (© 2024 The Authors.)

Objectives: Presurgical infant orthopedic appliances, such as presurgical nasoalveolar molding (PNAM) devices, are used to attain optimal conditions for primary repair of the lip and nose (PRoLN) in patients with cleft lip. We aimed to analyze the three-dimensional (3D) outcomes of PNAM using an LED surface scanner., Methods: Fifteen patients with unilateral cleft lip and palate (CLP) were included in this study and treated using a PNAM device. The patients' faces were digitized pre- and post-PNAM using an Artec Space Spider scanner, and the scanned data were analyzed using 3D software (Geomagic Control X and ANSYS SpaceClaim). The columellar angle (CA), nostril curvature (NC) on the affected (NC&#95;A) and unaffected (NC&#95;U) sides, gap of cleft lip (GCL), alar width (AW), and nasal tip angle (NTA) were measured., Results: CA increased significantly by 10.00° and NC&#95;A by 0.030 mm -1 (p < 0.001). GCL decreased by 4.98 mm 2 on average and NC&#95;U by 0.015 mm -1 (p = 0.029 and 0.046, respectively). AW also decreased by approximately 1.22 mm pre- and post-treatment (p = 0.002), and NTA, which shows a lateral profile, decreased by approximately 3.32° (p = 0.002)., Conclusions: This study confirmed the orthopedic benefits of PNAMd treatment through 3D analysis using an LED surface scanner. Further studies involving a larger number of participants are warranted to study the effects of PNAM and analyze longitudinal changes in patients with CLP., Clinical Significance: This study shows that PNAM effectively corrects columellar deviation and nostril shape in patients with unilateral cleft lip, with 3D scanners enhancing primary lip and nose repair outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Small molecules that exhibit broad-spectrum enteroviral inhibitory activity by targeting viral replication proteins are highly desired in antiviral drug discovery studies. To discover new human rhinovirus (hRV) inhibitors, we performed a high-throughput screening of 100,000 compounds from the Korea Chemical Bank library. This search led to identification of two phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) inhibitors having the pyrazolo-pyrimidine core structure, which display moderate anti-rhinoviral activity along with mild cytotoxicity. The results of a study aimed at optimizing the activity of the hit compounds showed that the pyrazolo-pyrimidine derivative 6f exhibits the highest activity (EC 50  = 0.044, 0.066, and 0.083 μM for hRV-B14, hRV-A16, and hRV-A21, respectively) and moderate toxicity (CC 50  = 31.38 μM). Furthermore, 6f has broad-spectrum activities against various hRVs, coxsackieviruses and other enteroviruses, such as EV-A71, EV-D68. An assessment of kinase inhibition potencies demonstrated that 6f possesses a high and selective kinase inhibition activity against PI4KIIIβ (IC 50 value of 0.057 μM) and not against PI4KIIIα (>10 μM). Moreover, 6f exhibits modest hepatic stability (46.9 and 55.3 % remaining after 30 min in mouse and human liver microsomes, respectively). Finally, an in vivo study demonstrated that 6f possesses a desirable pharmacokinetic profile reflected in low systemic clearance (0.48 L∙h -1  kg -1 ) and modest oral bioavailability (52.4 %). Hence, 6f (KR-26549) appears to be an ideal lead for the development of new antiviral drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Orthognathic surgery in patients with lip and palate clefts is challenging owing to scar tissue from primary repairs and severe deformities. In this study, we evaluated the stability of Le Fort I osteotomy with intraoral vertical ramus osteotomy (IVRO) in patients with cleft lip and palate using 3-dimensional (3D) analysis. This retrospective study comprised 14 cleft lip and palate patients (3 females, 11 males; the average age at surgery: 23.8 y) who underwent bimaxillary orthognathic surgery involving Lefort I osteotomy and IVRO. Cone-beam computed tomography (CBCT) images were obtained at preoperative (T0), 1-month postoperative (T1), and 1-year follow-up (T2) periods. The 3D analysis assessed the transitions and rotations of the maxilla and mandible using a virtual triangle. The maxilla showed stability in all directions at the 1-year follow-up with minimal relapse. The distal segment of the mandible exhibited clinically acceptable anterior (1.15 mm relapse) movements and pitch rotation (2.88° counterclockwise relapse) during the first year postoperatively. The proximal mandibular segment underwent anterior-inferior transition (1.21 and 2.01 mm, respectively) and lateral-outward rotation (4.90° and 7.51°, respectively) postsurgery, remaining unchanged 1 year postoperation. Le Fort I osteotomy with IVRO provides skeletal stability in patients with cleft lips and palates. This study demonstrated a minimal maxillary relapse and clinically acceptable movements in the distal mandibular segment during the first postoperative year. The proximal mandibular segment moved anteriorly and inferiorly, rotated laterally and outward after surgery, and remained unchanged at the 1-year follow-up., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

The rise in the prevalence of allergic diseases has become a global health burden. Allergic diseases are a group of immune-mediated disorders characterized by IgE-mediated conditions resulting from a type 2 helper T cell (Th2)-skewed immune response. This review aims to comprehensively summarize recent research on the roles of allergen immunotherapy (AIT) and biologics in allergic diseases. Specifically, we review the mechanisms of AIT and biologics in modulating innate and adaptive immunity involved in allergic disease pathogenesis, as well as their safety and efficacy in the treatment of allergic diseases. We also discuss current new AIT strategies such as recombinant allergen-based vaccines and allergen extract nanoencapsulation. Further research is needed to understand immune tolerance mechanisms beyond the Th2 pathway and to characterize immunological changes in responders and nonresponders to AIT or biologics. This additional research may uncover new targets for monitoring treatment responses and developing personalized treatment strategies for allergic diseases., Competing Interests: Declaration of Competing Interest Dr. Nadeau reports grants from National Institute of Allergy and Infectious Diseases (NIAID), National Heart, Lung, and Blood Institute (NHLBI), National Institute of Environmental Health Sciences (NIEHS), and Food Allergy Research & Education (FARE); Stock options from IgGenix, Seed Health, ClostraBio, Cour, Alladapt; Advisor at Cour Pharma; Consultant for Excellergy, Red tree ventures, Before Brands, Alladapt, Cour, Latitude, Regeneron, and IgGenix; Co-founder of Before Brands, Alladapt, Latitude, and IgGenix; National Scientific Committee member at Immune Tolerance Network (ITN), and National Institutes of Health (NIH) clinical research centers; patents include ‘Mixed allergen com-position and methods for using the same,’ ‘Granulocyte-based methods for detecting and monitoring immune system disorders,’ and ‘Methods and Assays for Detecting and Quantifying Pure Subpopulations of White Blood Cells in Immune System Disorders.’ The other authors have no conflicts of interest to report., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: Although hook plate fixation is popularly used, concerns exist regarding periprosthetic fractures and the necessity to remove the plate to prevent subacromial erosion and subsequent acromion fracture, due to its non-anatomical design. We hypothesized that a low profile 2.7 mm distal locking hook plate would provide comparable stability to a properly used 3.5 mm distal locking hook plate MATERIALS AND METHODS: A 3.5 mm distal locking plate (type 1) and a low profile 2.7 mm plate (type 2) were assessed by finite element analysis. Peak von Mises stress (PVMS) was calculated on the acromion's undersurface, clavicle shaft, and hook, focusing on how these stresses varied with the number and placement of distal locking screws., Results: Increased distal screws in both types led to lower PVMS on the acromion's undersurface and the hook, with the lowest acromion PVMS observed in type 2 with three distal screws, and on the hook in type 1 with two distal screws. Increasing the number of distal screws similarly reduced PVMS on the clavicle shaft, with the lowest in type 1 with two distal screws. In both plate types, the most posterior distal locking screw played a crucial role in distributing stress across the acromion and the hook., Conclusion: The low profile 2.7 mm distal locking hook plate showed comparable biomechanical results to the 3.5 mm distal locking hook plate. Increasing the number of distal locking screws showed less stress concentration on the bone and hook in both models. The most posterior distal locking screw showed an essential role in stress distribution., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. None of the researchers or an affiliated institute has received (or agreed to receive) from a commercial entity something of value (exceeding the equivalent of US$500) related in any way to this manuscript or research., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: Hypothermia is associated with poor outcomes in sepsis patients, and hypothermic sepsis patients exhibit temperature alterations during initial treatment. The objective of this study was to classify hypothermic sepsis patients based on body temperature trajectories and investigate the associations of these patients with 28-day mortality., Methods: This was a retrospective analysis of prospectively collected data from adult sepsis or septic shock patients who visited three emergency departments between August 2014 and December 2019. Hypothermic sepsis was defined as an initial body temperature <36 °C. delta temperature was calculated by subtracting the 0 h body temperature from the 6 h body temperature. We divided the patients into three groups according to delta temperature: Group A (delta temperature ≤ 0), Group B (0 < delta temperature ≤ 1) and Group C (delta temperature > 1). The primary outcome was 28-day mortality, and a multivariable Cox proportional hazards regression model was generated., Results: Among 7344 patients with sepsis or septic shock, 325 hypothermic patients were included in the analysis, and the overall mortality rate was 36%. While initial body temperature was not different between survivors and nonsurvivors, survivors exhibited a higher body temperature at 6 h. The 28-day mortality rates for Groups A, B and C were 53.1%, 36.0%, and 30.0%, respectively, and Group A had significantly higher mortality than Group C did (p < 0.05). Group C demonstrated a 44.2% decrease in 28-day mortality compared to Group A (adjusted hazard ratio of 0.558; 95% confidence interval of 0.330-0.941)., Conclusions: In hypothermic sepsis patients, an increase of 1 °C or more in body temperature after the initial 6 h is associated with a reduced risk of 28-day mortality., Competing Interests: Declaration of competing interest This study did not receive any sources of support that might pose a conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Herein, we report halide nanocomposite solid electrolytes (HNSEs) that integrate diverse oxides with alterations that allow tuning of their ionic conductivity, (electro)chemical stability, and specific density. A two-step mechanochemical process enabled the synthesis of multimetal (or nonmetal) HNSEs, MO 2 -2Li 2 ZrCl 6 , as verified by pair distribution function and X-ray diffraction analyses. The multimetal (or nonmetal) HNSE strategy increases the ionic conductivity of Li 2 ZrCl 6 from 0.40 to 0.82 mS cm -1 . Additionally, cyclic voltammetry test findings corroborated the enhanced passivating properties of the HNSEs. Notably, incorporating SiO 2 into HNSEs leads to a substantial reduction in the specific density of HNSEs, demonstrating their strong potential for achieving a high energy density and lowering costs. Fluorinated SiO 2 -2Li 2 ZrCl 5 F HNSEs exhibited enhanced interfacial compatibility with Li 6 PS 5 Cl and LiCoO 2 electrodes. Cells employing SiO 2 -2Li 2 ZrCl 5 F with LiCoO 2 exhibit superior electrochemical performance delivering the initial discharge capacity of 162 mA h g -1 with 93.7% capacity retention at the 100th cycle at 60 °C.

Achieving both formability and functionality in thermoelectric materials remains a significant challenge due to their inherent brittleness. Previous approaches, such as polymer infiltration, often compromise thermoelectric efficiency, underscoring the need for flexible, all-inorganic alternatives. This study demonstrates that the extreme brittleness of thermoelectric bismuth telluride (Bi 2 Te 3 ) bulk compounds can be overcome by harnessing the nanoscale flexibility of Bi 2 Te 3 nanoribbons and twisting them into a yarn structure. The resulting Bi 2 Te 3 yarn, with a Seebeck coefficient of -126.6 µV K -1 , exhibits remarkable deformability, enduring extreme bending curvatures (down to 0.5 mm -1 ) and tensile strains of ≈5% through over 1000 cycles without significant resistance change. This breakthrough allows the yarn to be seamlessly integrated into various applications-wound around metallic pipes, embedded within life jackets, or woven into garments-demonstrating unprecedented adaptability and durability. Moreover, a simple 4-pair thermoelectric generator comprising Bi 2 Te 3 yarns and metallic wires generates a maximum output voltage of 67.4 mV, substantiating the effectiveness of thermoelectric yarns in waste heat harvesting. These advances not only challenge the traditional limitations posed by the brittleness of thermoelectric materials but also open new avenues for their application in wearable and structural electronics., (© 2024 Wiley‐VCH GmbH.)