Background/Aims: Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients. Methods: We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19 to 79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes. Results: The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16-week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups.Each dosing regimen demonstrated significant decreases in RSI and RFS. Conclusions Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Background/Aims: Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients. Methods: We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19 to 79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes. Results: The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16-week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups.Each dosing regimen demonstrated significant decreases in RSI and RFS. Conclusions Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

Purpose: This study aimed to compare cognitive, non-cognitive, and overall learning outcomes for sepsis and trauma resuscitation skills in novices with virtual patient simulation (VPS) versus in-person simulation (IPS). Methods: A randomized controlled trial was conducted on junior doctors in 1 emergency department from January to December 2022, comparing 70 minutes of VPS (n=19) versus IPS (n=21) in sepsis and trauma resuscitation. Using the nominal group technique, we created skills assessment checklists and determined Bloom’s taxonomy domains for each checklist item. Two blinded raters observed participants leading 1 sepsis and 1 trauma resuscitation simulation. Satisfaction was measured using the Student Satisfaction with Learning Scale (SSLS). The SSLS and checklist scores were analyzed using the Wilcoxon rank sum test and 2-tailed t-test respectively. Results: For sepsis, there was no significant difference between VPS and IPS in overall scores (2.0; 95% confidence interval [CI], -1.4 to 5.4; Cohen’s d=0.38), as well as in items that were cognitive (1.1; 95% CI, -1.5 to 3.7) and not only cognitive (0.9; 95% CI, -0.4 to 2.2). Likewise, for trauma, there was no significant difference in overall scores (-0.9; 95% CI, -4.1 to 2.3; Cohen’s d=0.19), as well as in items that were cognitive (-0.3; 95% CI, -2.8 to 2.1) and not only cognitive (-0.6; 95% CI, -2.4 to 1.3). The median SSLS scores were lower with VPS than with IPS (-3.0; 95% CI, -1.0 to -5.0). Conclusion For novices, there were no major differences in overall and non-cognitive learning outcomes for sepsis and trauma resuscitation between VPS and IPS. Learners were more satisfied with IPS than with VPS (clinicaltrials.gov identifier: NCT05201950).

Background/Aims: Proton pump inhibitors (PPIs) play a crucial role in managing laryngopharyngeal reflux (LPR), but the optimal dosing regimen remains unclear. We aim to compare the effectiveness of the same total PPI dose administered twice daily versus once daily in LPR patients. Methods: We conducted a prospective randomized controlled trial at a tertiary referral hospital, enrolling a total of 132 patients aged 19 to 79 with LPR. These patients were randomly assigned to receive either a 10 mg twice daily (BID) or a 20 mg once daily (QD) dose of ilaprazole for 12 weeks. The Reflux Symptom Index (RSI) and Reflux Finding Score (RFS) were assessed at 8 weeks and 16 weeks. The primary endpoint was the RSI response, defined as a reduction of 50% or more in the total RSI score from baseline. We also analyzed the efficacy of the dosing regimens and the impact of dosing and duration on treatment outcomes. Results: The BID group did not display a higher response rate for RSI than the QD group. The changes in total RSI scores at the 8-week and 16-week visits showed no significant differences between the 2 groups. Total RFS alterations were also comparable between both groups.Each dosing regimen demonstrated significant decreases in RSI and RFS. Conclusions Both BID and QD PPI dosing regimens improved subjective symptom scores and objective laryngoscopic findings. There was no significant difference in RSI improvement between the 2 dosing regimens, indicating that either dosing regimen could be considered a viable treatment option.

Cellular senescence causes cell cycle arrest and promotes permanent cessation of proliferation. Since the senescence of mesenchymal stem cells (MSCs) reduces proliferation and multipotency and increases immunogenicity, aged MSCs are not suitable for cell therapy. Therefore, it is important to inhibit cellular senescence in MSCs. It has recently been reported that metabolites can control aging diseases. Therefore, we aimed to identify novel metabolites that regulate the replicative senescence in MSCs. Using a fecal metabolites library, we identified nervonic acid (NA) as a candidate metabolite for replicative senescence regulation. In replicative senescent MSCs, NA reduced senescence-associated β-galactosidase positive cells, the expression of senescence-related genes, as well as increased stemness and adipogenesis. Moreover, in non-senescent MSCs, NA treatment delayed senescence caused by sequential subculture and promoted proliferation. We confirmed, for the first time, that NA delayed and inhibited cellular senescence.Considering optimal concentration, duration, and timing of drug treatment, NA is a novel potential metabolite that can be used in the development of technologies that regulate cellular senescence.

Objectives: . This study evaluated the surgical outcomes of patients with Beckwith-Wiedemann syndrome who underwent tongue-reduction surgery and analyzed whether the malocclusion and mandibular prognathism caused by macroglossia could be improved. Methods: . A retrospective medical record review was performed for 11 patients with Beckwith-Wiedemann syndrome whose macroglossia was surgically treated. Demographic data, symptoms and signs, and intraoperative and postoperative surgical outcomes were evaluated. Surgery was performed by a single surgeon using the “keyhole” technique, involving midline elliptical excision and anterior wedge resection. Preoperative and postoperative plain skull lateral X-rays were evaluated to assess prognathism improvement. Results: . The median age at the time of surgery was 35.09 months, and the ratio of males to females was 4:7. The median surgical time was 98±31.45 minutes, and the median duration of the postoperative intensive care unit stay was 3.81±2.4 days. There were no airway complications. Two patients (18.2%) had postoperative wound dehiscence; however, there was no nerve damage, recurrence, or other complications. Among the five patients who underwent postoperative speech evaluation, all showed normal speech development, except one patient who had brain dysfunction and developmental delay. Measurements of the A point-nasion-B point (ANB) angles and sella-nasion-B point (SNB) angles (point A is the most concave point of the anterior maxilla; point B is the most concave point on the mandibular symphysis) on plain X-rays showed a significant decrease in the postoperative SNB angle (P <0.001) and a significant increase in the ANB angle (P <0.011). Conclusion . Tongue-reduction surgery is an effective and safe technique for severe forms of macroglossia associated with Beckwith-Wiedemann syndrome. In addition, it improves mandibular prognathism in young Beckwith-Wiedemann syndrome patients with macroglossia.

Background: To deliver therapeutics into the brain, it is imperative to overcome the issue of the blood-brain-barrier (BBB). One of the ways to circumvent the BBB is to administer therapeutics directly into the brain parenchyma. To enhance the treatment efficacy for chronic neurodegenerative disorders, repeated administration to the target location is required. However, this increases the number of operations that must be performed. In this study, we developed the IntraBrain Injector (IBI), a new implantable device to repeatedly deliver therapeutics into the brain parenchyma. Methods: We designed and fabricated IBI with medical grade materials, and evaluated the efficacy and safety of IBI in 9 beagles. The trajectory of IBI to the hippocampus was simulated prior to surgery and the device was implanted using 3D-printed adaptor and surgical guides. Ferumoxytol-labeled mesenchymal stem cells (MSCs) were injected into the hippocampus via IBI, and magnetic resonance images were taken before and after the administration to analyze the accuracy of repeated injection. Results: We compared the planned vs. insertion trajectory of IBI to the hippocampus.With a similarity of 0.990 ± 0.001 (mean ± standard deviation), precise targeting of IBI was confirmed by comparing planned vs. insertion trajectories of IBI. Multiple administrations of ferumoxytol-labeled MSCs into the hippocampus using IBI were both feasible and successful (success rate of 76.7%). Safety of initial IBI implantation, repeated administration of therapeutics, and long-term implantation have all been evaluated in this study. Conclusion Precise and repeated delivery of therapeutics into the brain parenchyma can be done without performing additional surgeries via IBI implantation.

Objective: The purpose of this study is to examine the effect of high mobility group AT-hook 1 (HMGA1) on the phenotyptic change of vascular smooth muscle cells (VSMCs). Methods: Gene silencing and overexpression of HMGA1 were introduced to evaluate the effect of HMGA1 expression on the phenotypic change of VSMCs. Marker gene expression of VSMCs was measured by promoter assay, quantitative polymerase chain reaction, and western blot analysis. Common left carotid artery ligation model was used to establish in vivo neointima formation. Results: HMGA1 was expressed strongly in the synthetic type of VSMCs and significantly downregulated during the differentiation of VSMCs. Silencing of HMGA1 in the synthetic type of VSMCs enhanced the expression of contractile marker genes thereby enhanced angiotensin II (Ang II)-dependent contraction, however, significantly suppressed proliferation and migration. Stimulation of contractile VSMCs with platelet-derived growth factor (PDGF) enhanced HMGA1 expression concomitant with the downregulation of marker gene expression which was blocked significantly by the silencing of HMGA1. Silencing of HMGA1 retained the Ang II-dependent contractile function, which was curtailed by PDGF stimulation, however, overexpression of HMGA1 in the contractile type of VSMCs suppressed marker gene expression. Proliferation and migration were enhanced significantly by the overexpression of HMGA1. Furthermore, the Ang II-dependent contraction was reduced significantly by the overexpression of HMGA1. Finally, the expression of HMGA1 was enhanced significantly in the ligated artery, especially in the neointima area. Conclusion HMGA1 plays an essential role in the phenotypic modulation of VSMCs.Therefore, paracrine factors such as PDGF may affect vascular remodeling through the regulation of HMGA1.