Genetic variation in the leptin receptor (LEPR) gene has been implicated in metabolic regulation, while the gut microbiome and circulating metabolites are increasingly recognized as mediators of host metabolic phenotype. However, the systems-level interactions among LEPR genotypes, gut microbial composition, and serum metabolomic profiles remain poorly understood, particularly in healthy individuals. We conducted a cross-sectional study involving 37 healthy Korean adults. Three LEPR single nucleotide polymorphisms (rs1137101, rs1173100, rs790419) were genotyped. Untargeted metabolomics of fasting serum was performed using gas chromatography–time-of-flight mass spectrometry, and gut microbiome composition was profiled by 16S rRNA gene sequencing. Statistical analysis included principal component analysis, Mann–Whitney U tests, and Spearman correlations. Network analysis integrating microbiome, metabolomic, and clinical phenotype data was conducted using Cytoscape. A total of 54 serum metabolites were identified. LEPR genotypes, particularly rs1137101 and rs1173100, were associated with differences in metabolites such as pimelic acid, malonic acid, and 2,4-dihydroxybutyric acid. Firmicutes negatively correlated with saturated fatty acids and organic acids, whereas Actinobacteria positively correlated with cholesterol and amino acids. Network analysis revealed indole-3-acetate and cholesterol as central nodes linking microbial taxa with body mass index and leptin levels. However, no direct molecular pathways connecting leptin or its receptor were identified. LEPR genetic variation is associated with distinct serum metabolomic patterns and microbiome–host networks in healthy adults. Although no direct leptin signaling links were found, network-level associations suggest indirect genetic influences on metabolic states through microbiome–metabolome interactions.These findings advance understanding of personalized metabolic regulation and gene–microbiome interplay.

The comprehensive in vitro proarrhythmia assay (CiPA) initiative, led by the U.S. Food and Drug Administration (FDA), provides a framework for predicting drug-induced arrhythmia risk. To support domestic CiPA implementation, we evaluated the proarrhythmic risk of sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor. Sildenafil has been misused recreationally, with reports of highdose non-medical intake. To simulate misuse, in vitro assays were conducted using concentrations up to 100× the maximum therapeutic plasma concentration (Cmax). The assessment followed the three core components of the CiPA paradigm. Patch clamp assays were conducted in Human Embryonic Kidney 293 (HEK293) and Chinese hamster ovary (CHO) cells transiently expressing Nav1.5, Cav1.2, and hERG ion channels. In silico modeling was performed using the CiPAORdv1.0 model based on IC₅₀ and Hill coefficient values. Functional evaluation included multi-electrode array (MEA) recordings in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), and in vivo electrocardiography (ECG) analysis in rats was performed to observe QT interval prolongation. Sildenafil significantly inhibited hERG currents by 40.5% at 100× Cmax. In silico modeling predicted a low Torsades de Pointes (TdP) risk based on qNet biomarkers. In contrast, MEA recordings showed a concentration-dependent prolongation of corrected field potential duration (FPDc), with a significant 13.3% increase at 100× Cmax. The TdP risk estimated from MEA modeling was 64%. In vivo ECG analysis revealed significant QT prolongation at 50× Cmax. Despite low in silico TdP predictions, functional assays suggest that high concentrations of sildenafil as in misuse may pose a clinically relevant risk of QT prolongation and arrhythmia.

Endocrine-disrupting chemicals (EDCs) and persistent organic pollutants (POPs) cross the placenta and accumulate during gestation and early postnatal life, periods of heightened hormonal and neurodevelopmental plasticity. Exposure to contaminants such as bisphenol A (BPA), phthalates, polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) during these critical windows can reprogram endocrine and neural circuits, resulting in persistent behavioral alterations. This review synthesizes mechanistic evidence from animal models and epidemiological studies linking developmental EDC/POP exposure to attention deficits, impulsivity, anxiety and altered reward sensitivity—phenotypes defined here as addiction vulnerability (addiction-relevant endophenotypes) rather than clinically diagnosed substance-use disorder (SUD). We propose a two-hit, adverse outcome pathway (AOP)-informed model in which prenatal EDC/POP exposure induces endocrine-related perturbations that prime reward and stress circuitry. Subsequent exposure to psychoactive drugs and/or chronic stress then acts on these sensitized systems to increase the probability of maladaptive reinforcement learning and impaired behavioral control. Mechanistically, early-life exposures disrupt thyroid and sex-steroid signaling, dysregulate the hypothalamic–pituitary–adrenal axis, and alter dopaminergic, serotonergic, and glutamatergic neurotransmission with additional modulation by epigenetic reprogramming, oxidative stress, and neuroinflammation. Human cohort studies consistently associate prenatal BPA and phthalate exposures with adverse neurobehavioral and externalizing symptoms in children, supporting this framework while underscoring the limited availability of longitudinal data linking early exposure to SUD outcomes. Integrating these findings within an AOP perspective highlights the importance of developmental timing, sex, dose, genetic background, and co-exposures, and supports risk-assessment strategies that account for sequential environmental and drug exposures.

Subglottic stenosis (SGS) and tracheal stenosis (TS) are rare conditions that can cause significant breathing difficulties and, if not properly managed, may lead to life-threatening complications. Despite their clinical importance, debate continues regarding the optimal management of adult SGS and TS, and no comprehensive guidelines have been established to date. The Korean Bronchoesophagological Society appointed a task force to develop clinical practice guidelines with the goal of providing evidence-based recommendations for managing SGS and TS in adults. The task force conducted a systematic review of the relevant literature by searching PubMed, Embase, and the Cochrane Library using predefined search terms aligned with key clinical questions. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which also informed the formulation and reporting of the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for eligible patients. After drafting the guidelines, feedback was obtained through Delphi questionnaires completed by members of the Korean Bronchoesophagological Society. Ultimately, the committee developed 17 evidence-based recommendations across four categories: initial evaluation, medical management, surgical treatment, and postoperative management and rehabilitation. These guidelines aim to support clinicians in delivering optimal care to adult patients with SGS and TS.

This study investigated the relationship between the perceptions and consumption patterns of alternative sweetener (AS) foods among healthy young adults.We surveyed and classified two hundred and fifty adults aged 20~30 years residing in Hwaseong-si into high- and low-intake groups based on the frequency of AS beverage consumption. Data were collected using self-administered questionnaires assessing general characteristics, awareness, purchasing behavior, satisfaction, dietary habits, and health management behaviors, followed by correlation analyses. The high-intake group showed significantly higher awareness of specific sweeteners, including aspartame, sucralose, erythritol, and maltitol (P<0.05). The high-intake group was also more likely to check nutrition labeling (P<0.05) and identify diet- and health-related factors as primary purchase motives (P<0.001). Although overall satisfaction with AS foods was above average in both groups, it was significantly higher in the high-intake group (P<0.001). General dietary behaviors did not differ substantially between groups, but carbonated beverage consumption was significantly higher in the high-intake group (P<0.001). Regarding health-related behaviors, individuals in the high-intake group were more likely to perceive themselves as slightly overweight (P<0.05) and reported a higher frequency of weight control efforts (P<0.05). Correlation analysis confirmed a significant positive association between overall intake frequency and overall perception of AS. In conclusion, favorable perceptions of ASs are associated with higher consumption and purchase intentions, while consumption patterns vary according to the type of use. Nevertheless, limited detailed knowledge highlights the need for improved nutrition labeling and consumer education to support informed consumption.

Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

Objective: : To identify sex-specific risk factors for postoperative urinary retention (POUR) in patients undergoing spine surgery with total intravenous anesthesia (TIVA) and explore differences between male and female patients. Methods: : A retrospective chart review was conducted on 446 adult patients (268 males, 178 females) who underwent spine surgery with TIVA from January 1, 2019 to December 31, 2023. Propensity score matching was applied to adjust for confounding variables, resulting in 328 matched patients (164 males and 164 females). Multivariable logistic regression analyses were performed to identify independent risk factors for POUR. Residual urine volume ≥300 mL was used to define POUR. Results: : Male patients had a higher incidence of POUR compared to female patients. Significant risk factors for POUR in males included myelopathy (adjusted odds ratio [aOR], 5.17; 95% confidence interval [CI], 1.11–24.15), benign prostatic hyperplasia (BPH) (aOR, 2.63; 95% CI, 1.02–6.78), and prolonged anesthesia time ≥240 minutes (aOR, 2.54; 95% CI, 1.13–5.72). No significant risk factors were found in female patients. Myelopathy and prolonged anesthesia were associated with an increased risk of POUR across the overall population. Conclusion : Male sex, myelopathy, BPH, and prolonged anesthesia time are significant risk factors for POUR following spine surgery with TIVA. Given these findings, particular attention should be paid to myelopathy, a history of BPH, and anesthesia time in male patients.

Subarachnoid hemorrhage (SAH) is a stroke subtype with high mortality and poor functional outcomes. Prompt occlusion of a ruptured aneurysm at an early stage is crucial to prevent rebleeding, which can result in even higher mortality and more severe disabilities. The most critical initial decision in SAH management is the choice of treatment method with surgical clipping or endovascular coiling. We aimed to develop an evidence-based clinical guideline to select the optimal initial treatment in patients with SAH. We developed this guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted across four databases (MEDLINE, Embase, Cochrane, and KoreaMed) to answer two population, intervention, comparison, outcome questions comparing clipping and coiling. The risk of bias was assessed using ROB 2.0 and the Newcastle-Ottawa Scale. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagrams and meta-analyses were generated for functional outcome and mortality. We included six randomized control trials (RCTs) and 58 observational studies. Meta-analysis of RCTs showed that coiling improved functional outcomes compared to clipping (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.86–0.97). No significant mortality difference was observed in RCTs (OR, 1.38; 95% CI, 0.91–2.09), but non-RCTs favored clipping for reduced mortality (OR, 0.77; 95% CI, 0.69–0.86). However, it is difficult to generalize these findings to all clinical situations, as patients with SAH have a highly variable clinical course. Final treatment decision should be tailored to the individual patient’s status, including aneurysm location, morphology, and the expertise available at the treatment center. Such decisions are best made by specialists such as a board-certified physician and should be explained to the patient and their caregivers, along with the rationale for selecting the most appropriate treatment at the given hospital. Korea has many certified endovascular neurosurgeons, cerebrovascular surgeons, and certified cerebrovascular centers. Proper selection of the most suitable treatment method by certified physicians and centers would greatly benefit patient outcomes and healthcare professionals.

Accurate and early identification of stroke and large vessel occlusion (LVO) in emergency settings is essential for improving patient outcomes and ensuring the efficient allocation of medical resources. This clinical practice guideline systematically reviews domestic and international literature and conducts meta-analyses to evaluate the utility and diagnostic accuracy of stroke assessment tools used in prehospital emergency medical services (EMS). We developed a guideline based on evidence from systematic reviews and meta-analyses via a de novo process. A systematic literature review was conducted to evaluate the usefulness of diagnostic EMS assessment tools for diagnosing stroke and LVO. Overall, 70 non-randomized control studies were selected for this study. A meta-analysis was conducted with a subgroup analysis to distinguish between patients with stroke and those with LVO. EMS tools demonstrated high sensitivity but low specificity for diagnosing stroke. In the prehospital setting, using validated EMS stroke assessment tools is recommended for the early identification of stroke and LVO. Upon hospital arrival, stroke specialists should conduct further evaluation and triage to confirm the diagnosis and guide appropriate management. Delays in diagnosing LVO are frequently unacceptable. While experts advocate for the use of EMS assessment tools to facilitate early identification of LVO, these tools alone lack adequate sensitivity. Therefore, further diagnostic evaluations and consultation with stroke specialists upon hospital arrival are recommended.