Androgen deprivation-induced senescence confers sensitivity to a senolytic strategy in prostate cancer.

We have previously demonstrated that androgen-dependent prostate cancer (PCa) cell lines enter a state of senescence following exposure to androgen deprivation therapies (ADT). ADT-induced senescence was found to be transient, as senescent cells develop castration resistance and re-emerge into a proliferative state even under continuous androgen deprivation in vitro. Moreover, the BCL-XL/BCL-2 inhibitor, ABT-263 (navitoclax), an established senolytic agent, promoted apoptosis of senescent PCa cells, suppressing proliferative recovery and subsequent tumor cell outgrowth. As this strategy has not previously been validated in vivo, we used a clinically relevant, syngeneic murine model of PCa, where mice were either castrated or castrated followed by the administration of ABT-263. Our results largely confirm the outcomes previously reported in vitro; specifically, castration alone results in a transient tumor growth suppression with characteristics of senescence, which is prolonged by exposure to ABT-263. Most critically, mice that underwent castration followed by ABT-263 experienced a statistically significant prolongation in survival, with an increase of 14.5 days in median survival time (56 days castration alone vs. 70.5 days castration + ABT-263). However, as is often the case in studies combining the promotion of senescence with a senolytic (the "one-two" punch approach), the suppression of tumor growth by the inclusion of the senolytic agent was transient, allowing for tumor regrowth once the drug treatment was terminated. Nevertheless, the results of this work suggest that the "one-two" punch senolytic strategy in PCa may effectively interfere with, diminish, or delay the development of the lethal castration-resistant phenotype.

Comparative Effectiveness of a Second Tumor Necrosis Factor Inhibitor Versus a Non-Tumor Necrosis Factor Biologic in the Treatment of Patients With Polyarticular-Course Juvenile Idiopathic Arthritis.

OBJECTIVE: The objective of this study was to compare the effectiveness of a second tumor necrosis factor inhibitor (TNFi) versus a non-TNFi biologic following discontinuation of a TNFi for patients with polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: Using the Childhood Arthritis and Rheumatology Research Alliance Registry, patients with pJIA who started receiving a second biologic following a first TNFi were identified. Patients were required to have no active uveitis on the index date and a visit six months after the index date. Outcome measures included Clinical Juvenile Arthritis Disease Activity Score with a maximum of 10 active joints (cJADAS10), cJADAS10 inactive disease (ID; ≤2.5) and cJADAS10 minimal disease activity (MiDA; ≤5). Multiple imputation was used to account for missing data. Adjusted odds ratios (aORs) were calculated using propensity score quintiles to compare outcomes at six months following second biologic initiation. RESULTS: There were 216 patients included, 84% initially received etanercept, and most patients stopped receiving it because of its ineffectiveness (74%). A total of 183 (85%) started receiving a second TNFi, and 33 (15%) started receiving a non-TNFi. Adalimumab was the most common second biologic received (71% overall, 84% of second TNFi), and tocilizumab was the most common non-TNFi second biologic received (9% overall, 58% of non-TNFi). There was no difference between receiving TNFi versus non-TNFi in cJADAS10 ID (29% vs 25%; aOR 1.23, 95% confidence interval [CI] 0.47-3.20) or at least MiDA (43% vs 39%; aOR 1.11, 95% CI 0.47-2.62) at six months. CONCLUSION: Most patients with pJIA started receiving TNFi rather than non-TNFi as their second biologic, and there were no differences in disease activity at six months.

Sex-specific genetic architecture of blood pressure.

The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (Pfemale ≤ 5 × 10-8; Pmale > 5 × 10-8) and 142 were male-specific (Pmale ≤ 5 × 10-8; Pfemale > 5 × 10-8); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1. Analyses of gene-by-sex interactions and sexually dimorphic effects identified four genomic regions, showing female-specific associations with diastolic BP or pulse pressure, including the chromosome 13q34-COL4A1/COL4A2 locus. Notably, female-specific pulse pressure-associated loci exhibited enriched acetylated histone H3 Lys27 modifications in arterial tissues and a female-specific association with fibromuscular dysplasia, a female-biased vascular disease; colocalization signals included Chr13q34: COL4A1/COL4A2, Chr9p21: CDKN2B-AS1 and Chr4q32.1: MAP9 regions. Sex-specific and sex-biased polygenic associations of BP traits were associated with multiple cardiovascular traits. These findings suggest potentially clinically significant and BP sex-specific pleiotropic effects on cardiovascular diseases.

Collaborative relationships between doulas and maternity care providers when supporting migrant women during labour and birth.

OBJECTIVE: To explore the perspectives and experiences of community-based doulas and maternity care providers working with each other in Australia; and to identify the facilitators and barriers to working relationships when supporting migrant women during labour and birth. DESIGN AND METHODS: A qualitative interpretive phenomenological study using in-depth semi-structured interviews. An inductive thematic approach and Capability, Opportunity, and Motivation (COM-B) framework were used in data analysis. SETTING AND PARTICIPANTS: 10 doulas from Birth for Humankind (a community-based doula service), and 13 maternity care providers from a tertiary maternity hospital in Melbourne, Australia were included. FINDINGS: We identified how collaborative working relationships between community-based doulas and maternity care providers may be enhanced by adopting facilitators across all three COM-B domains and by removing identified barriers. Factors facilitating collaborative working relationships included: knowledge and value of doula roles, establishment of rapport and trust between doulas and providers; doulas enhancing respectful care, communication and relationships between migrant women and providers; and community-based doulas differentiated from private practising doulas. Barriers included: limited understanding of doula roles and service; limiting behaviours impacting collaborative relationships; and limited opportunities for doulas and providers to establish rapport. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Findings are relevant to other models of doula care including private practice doulas and hospital-based doula services. Positive, collaborative doula-provider working relationships are integral for ensuring that the benefits of doula care continue to reach underserved populations such as migrant women and improve their maternity care experiences and outcomes within hospitals settings.

Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation.

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

A qualitative study on community-based doulas' roles in providing culturally-responsive care to migrant women in Australia.

BACKGROUND: There is limited exploration into how culturally-responsive care may be provided to migrant women through community-based doulas. AIM: We aim to explore the roles of community-based doulas in providing culturally-responsive care to migrant women in Australian maternity settings, from the perspectives of maternity care providers and doulas. METHODS: We used an interpretive phenomenological qualitative approach with in-depth interviews with 30 maternity care providers and Birth for Humankind doulas, in Victoria, Australia. All interviews were conducted over video-call and inductive thematic analysis was performed using NVivo software. FINDINGS: Doulas were seen to support and enhance migrant women's maternity care experiences through numerous ways, strengthening cultural-responsive care provision. There were three domains which described the role of doulas in providing migrant women with culturally-responsive care: 1) enhanced care; 2) respectful care; and 3) supportive relationships with providers. The three domains included seven themes: 1) continuous individualised support; 2) social connectedness; 3) creating safe spaces; 4) cultural facilitator; 5) non-judgemental support; 6) enhancing communication and rapport with providers; and 7) making connections. DISCUSSION: Doulas appeared to counter negative factors that impact migrant women's maternity care experiences. Doulas with previous professional birth support qualifications and trauma-informed care training were equipped to create safe spaces and increase emotional safety for migrant women. Doulas may also have more responsibilities expected of them by providers when connecting migrant women with additional services in situations that may be missed through hospital care. CONCLUSION: Birth for Humankind doulas in Victoria play an important role in providing culturally-responsive care to migrant women. Employment models may be the next steps in acknowledging their valuable contribution as a complementary service to maternity settings.

Association between the dual use of electronic and conventional cigarettes and NAFLD status in Korean men.

INTRODUCTION: This study investigated the association between smoking types, including dual use (usage of both combustible cigarettes and e-cigarettes), and non-alcoholic fatty liver disease (NAFLD) status in Korean men. METHODS: Data from the 7th and 8th Korea National Health and Nutrition Examination Survey (KNHANES) 2016-2020 were used. The presence of NAFLD was defined by the respective cut-off values for the Hepatic Steatosis Index (HSI), NAFLD Ridge Score (NRS), and Korea National Health and Nutrition Examination Survey NAFLD score (KNS). Multivariate logistic regression analyses were used to determine the associations between smoking types and NAFLD as determined by HSI, NRS, and KNS. RESULTS: After adjustment for confounders, an independent association was observed between dual use and NAFLD (HSI: AOR=1.47; 95% CI: 1.08-1.99, p=0.014; NRS: AOR=2.21; 95% CI: 1.70-2.86, p=0.000; KNS: AOR=1.35; 95% CI: 1.01-1.81, p=0.045). Cigarette only smokers also had significantly higher odds of NAFLD compared to never smokers for all of the NAFLD indices (HSI: AOR=1.22; 95% CI: 1.05-1.42, p=0.008; NRS: AOR=2.13; 95% CI: 1.87-2.42, p=0.000; KNS: AOR=1.33; 95% CI: 1.14-1.55, p=0.000). In subgroup analyses, no significant interaction effects were found for age, BMI, alcohol consumption, income, physical activity, and the diagnosis of T2DM. Moreover, cigarette only smokers and dual users differed significantly in terms of log-transformed urine cotinine and pack-years. The relationship between smoking type and pack-years was attenuated after stratification by age. CONCLUSIONS: This study shows that the dual use of e-cigarettes and combustible cigarettes is associated with NAFLD. Age differences may explain why dual users, with a greater proportion of young people, appear to have fewer pack-years than cigarette only smokers. Further research should be conducted to investigate the adverse effects of dual use on hepatic steatosis.

Repurposing a Cyclin-Dependent Kinase 1 (CDK1) Mitotic Regulatory Network to Complete Terminal Differentiation in Lens Fiber Cells.

Purpose: During lens fiber cell differentiation, organelles are removed in an ordered manner to ensure lens clarity. A critical step in this process is removal of the cell nucleus, but the mechanisms by which this occurs are unclear. In this study, we investigate the role of a cyclin-dependent kinase 1 (CDK1) regulatory loop in controlling lens fiber cell denucleation (LFCD). Methods: We examined lens differentiation histologically in two different vertebrate models. An embryonic chick lens culture system was used to test the role of CDK1, cell division cycle 25 (CDC25), WEE1, and PP2A in LFCD. Additionally, we used three mouse models that express high levels of the CDK inhibitor p27 to test whether increased p27 levels affect LFCD. Results: Using chick lens organ cultures, small-molecule inhibitors of CDK1 and CDC25 inhibit LFCD, while inhibiting the CDK1 inhibitory kinase WEE1 potentiates LFCD. Additionally, treatment with an inhibitor of PP2A, which indirectly inhibits CDK1 activity, also increased LFCD. Three different mouse models that express increased levels of p27 through different mechanisms show impaired LFCD. Conclusions: Here we define a conserved nonmitotic role for CDK1 and its upstream regulators in controlling LFCD. We find that CDK1 functionally interacts with WEE1, a nuclear kinase that inhibits CDK1 activity, and CDC25 activating phosphatases in cells where CDK1 activity must be exquisitely regulated to allow for LFCD. We also provide genetic evidence in multiple in vivo models that p27, a CDK1 inhibitor, inhibits lens growth and LFCD.

Childhood Acid Suppressants May Increase Allergy Risk-A Systematic Review and Meta-Analysis.

BACKGROUND: Recent studies suggest that the use of acid suppressants in early childhood may increase the risk of allergic diseases. OBJECTIVE: To systematically review and synthesize associations between the childhood use of acid suppressants and development of allergic diseases. METHODS: PubMed, Embase, The Cochrane Library, and Scopus were searched using a systematic search strategy. We included observational or interventional studies that looked at the use of acid suppressants in the pediatric population, in association with allergic outcomes such as asthma, atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and food allergies. Key data were extracted and risk of bias was evaluated according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines and a PROSPERO-registered protocol. Maximally adjusted estimates were pooled using mixed-effects models, and heterogeneity was measured using I2. Further subgroup and sensitivity analyses were conducted. Overall quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations framework. RESULTS: This review included 5 observational studies from 1977 records with low-to-moderate risk of bias. Childhood acid-suppressant use was associated with significantly increased hazards of asthma (hazard ratio [HR] = 1.44, 95% confidence interval [CI] = 1.31-1.58), atopic dermatitis (HR = 1.12, 95% CI = 1.10-1.14), and allergic rhinitis (HR = 1.40, 95% CI = 1.24-1.58). These associations were adjusted for confounders such as demographics, parental educational level, and use of antibiotics. Overall quality of evidence was low. CONCLUSIONS: Childhood use of acid suppressants may increase the risk of incident asthma, atopic dermatitis, and allergic rhinitis. However, larger studies such as randomized controlled trials are needed to determine causality. These drugs should be used judiciously in pediatric patients, and more stringent guidelines should be advocated.

How many times should we repeat measurements of the ultrasound-guided attenuation parameter for evaluating hepatic steatosis?

Purpose@#This retrospective study aimed to determine the number of times the ultrasound-guided attenuation parameter (UGAP) should be measured during the evaluation of hepatic steatosis. @*Methods@#Patients with suspected nonalcoholic fatty liver disease who underwent two UGAP repetition protocols (six-repetition [UGAP_6] and 12-repetition [UGAP_12]) and measurement of the controlled attenuation parameter (CAP) using transient elastography between October 2020 and June 2021 were enrolled. The mean attenuation coefficient (AC), interquartile range (IQR)/median, and coefficient of variance (CV) of the two repetition protocols were compared using the paired t test. Moreover, the diagnostic performances of UGAP_6 and UGAP_12 were compared using the area under the receiver operating characteristic (AUROC) curve, considering the CAP value as a reference standard. @*Results@#The study included 160 patients (100 men; mean age, 50.9 years). There were no significant differences between UGAP_6 and UGAP_12 (0.731±0.116 dB/cm/MHz vs. 0.734±0.113 dB/cm/MHz, P=0.156) and mean CV (7.6±0.3% vs. 8.0±0.3%, P=0.062). However, the mean IQR/median of UGAP_6 was significantly lower than that of UGAP_12 (8.9%±6.0% vs. 9.8%±5.2%, P=0.012). In diagnosing the hepatic steatosis stage, UGAP_6 and UGAP_12 yielded comparable AUROCs (≥S1, 0.908 vs. 0.897, P=0.466; ≥S2, 0.883 vs. 0.897, P=0.126; S3, 0.832 vs. 0.834, P=0.799). @*Conclusion@#UGAP had high diagnostic performance in diagnosing hepatic steatosis, regardless of the number of repetitions (six repetitions vs. 12 repetitions), with maintained reliability. Therefore, six UGAP measurements seem sufficient for evaluating hepatic steatosis using UGAP.

Intra-individual comparison of two-dimensional shear wave elastography techniques using plane wave imaging and the multi-beam technique: are they interchangeable in measuring liver fibrosis?

Purpose@#This study compared two different two-dimensional shear wave elastography techniques—plane wave imaging (PWI) and multi-beam (MB) imaging—from the same vendor to evaluate liver fibrosis. @*Methods@#In this prospective study, 42 patients with chronic liver disease who had recently undergone magnetic resonance elastography (<3 months) were enrolled, and their liver stiffness (LS) values were measured using PWI or MB. The LS values (kPa) were compared using the Wilcoxon rank-sum test. Inter-technique reproducibility and intra-observer repeatability were assessed using Bland-Altman analysis with 95% limits of agreement (LOA) and coefficients of variation (CVs). The cutoff values for predicting severe fibrosis (≥F3) were estimated using receiver operating characteristic curve (ROC) analysis, with magnetic resonance elastography as the reference standard. @*Results@#PWI exhibited technical failure in four patients. Therefore, 38 patients underwent both examinations. The LS values showed moderate agreement between PWI and MB (CV, 22.5%) and 95% LOA of -3.71 to 7.44 kPa. The MB technique showed good intra-observer agreement (CV, 8.1%), while PWI showed moderate agreement (CV, 11.0%). The cutoff values of PWI and MB for diagnosing ≥F3 were 12.3 kPa and 13.8 kPa, respectively, with areas under the ROC curve of 0.89 and 0.95 (sensitivity, 100% and 100%; specificity, 65.6% and 85.7%). @*Conclusion@#The LS values significantly differed between PWI and MB, hindering their interchangeable use in longitudinal follow-up. Considering its low technical failure rate and better repeatability, the MB technique may be preferable for evaluating liver fibrosis in chronic liver disease patients.

Surgical Result of Resection of Benign Neoplasm on the External Auditory Canal Using Transcanal Endoscopic Ear Surgery / 대한이비인후과학회지

Various benign neoplasms such as osteoma, cholesteatoma, and cartilaginous choristoma can occur in the external auditory canal. The treatment method for these benign neoplasms is surgical excision. Previously, surgery had been performed using a microscope, but recently, a transcanal endoscopic ear surgery (TEES) method has been attempted. As a surgical method, it provides a better surgical view, enables rapid recovery and reduces pain through a minimally invasive approach. In this article, we introduce this endoscopic removal surgical method for benign neoplasms of the external auditory canal and the usefulness of the method.

Morphological Comparison of Posterior Malleolar Fractures in Tibial Spiral Fractures and Ankle Fractures / 대한정형외과학회잡지

Purpose@#This study morphologically compared and analyzed various measurements from initial radiograph and computed tomography scans of posterior malleolar fractures (PMFs) in tibial spiral fractures and ankle fractures. @*Materials and Methods@#The measurements of PMFs in 31 TSFs and 53 AFs were analyzed. PMFs were classified using Bartoníček’s classification. The initial displacement (ID), cross angle (CA), fragment length ratio (FLR), fragment width ratio (FWR), fragment height ratio (FHR), fragment height (FH), sagittal angle (SA), articular step-off (AS), and inter-fragment distance (IFD) were measured. The presence of intercalary fragments and articular incongruity were identified. @*Results@#Bartoníček types 2 and 3 in the AF group, type 3 in the supination-external rotation (SER) group, type 2 in the pronation-external rotation (PER) group, and type 4 in the TSF group accounted for the largest proportion. In the TSF group, the mean ID, FWR, SA, AS, and IFD were significantly smaller than in the AF group (p<0.001, p=0.003, p<0.001, p<0.001, and p<0.001, respectively). The CA, FLR, FH, and FHR were significantly larger than the AF group (p<0.001, p=0.019, p<0.001, and p<0.001, respectively). @*Conclusion@#In TSFs, posterior malleolar fragments tend to have longer anteroposterior lengths and heights, but shorter horizontal lengths than AFs. Most have minimal displacement, congruous joint, and no intercalary fragments. Understanding these morphological differences is necessary for the clinical approach to PMFs in TSFs and AFs.

Predictive role of absolute lymphocyte count in daratumumab-treated patients with relapsed/ refractory multiple myeloma

Background/Aims@#Daratumumab has shown an encouraging antitumor effect in patients with multiple myeloma (MM), and was known to alter the immune properties by off-targeting immunosuppressive cells. Here, we aimed to evaluate the change in absolute lymphocyte count (ALC) as a surrogate marker for predicting survival outcomes of patients treated with daratumumab. @*Methods@#Between 2018 and 2021, the medical records of patients with relapsed/refractory MM (RRMM) treated with daratumumab monotherapy at 10 centers in South Korea were reviewed. We collected the ALC data at pre-infusion (D0), day 2 after the first infusion (D2), and prior to the third cycle of daratumumab therapy (D56). @*Results@#Fifty patients who were administered at least two cycles of daratumumab were included. Overall response rate was 54.0% after two cycles of daratumumab treatment. On D2, almost all patients experienced a marked reduction in ALC. However, an increase in ALC on D56 (ALCD56) was observed in patients with non-progressive disease, whereas failure of ALC recovery was noted in those with progressive disease. Patients with ALCD56 > 700/μL (n = 39, 78.0%) had prolonged progression- free survival (PFS) and overall survival (OS) than those with ALCD56 ≤ 700/μL (median PFS: 5.8 months vs. 2.6 months, p = 0.025; median OS: 24.1 months vs. 6.1 months, p = 0.004). In addition, ALCD56 >700/μL was a significant favorable prognostic factor for PFS (hazard ratio [HR], 0.22; p = 0.003) and OS (HR, 0.23; p = 0.012). @*Conclusions@#Increase in ALC during daratumumab treatment was significantly associated with prolonged survival outcomes in patients with RRMM. The ALC value can predict clinical outcomes in patients treated with daratumumab.

Increased Right Dorsolateral Prefrontal Cortex Connectivity During Emotion Recognition Task in Adolescents With Self-Injurious Behavior: A Functional Near-Infrared Spectroscopy Study

Objective@#Research on neural correlates in the prefrontal cortex (PFC) associated with self-injurious behavior has mainly been performed in adults. However, studies on adolescents are scarce. We aimed to investigate the activation and connectivity of the PFC between adolescents with self-injurious behavior (ASI) and psychiatric controls (PC) using functional near-infrared spectroscopy (fNIRS). @*Methods@#We used an emotion recognition task during fNIRS to assess 37 adolescents (23 with self-injurious behavior and 14 PC) between June 2020 and October 2021 and compared connectivity and activation between the two groups. We also measured adverse childhood events (ACE, Adverse Childhood Experiences) and performed a correlation analysis of channel activation according to ACE total scores. @*Results@#The difference in activation between the groups was not statistically significant. The connectivity of channel 6 was statistically significant. The interaction between channel 6 and the ACE total score showed statistical significance between the two groups(t[33] -2.61; p=0.014). The ASI group showed a negative correlation with the total ACE score. @*Conclusion@#This is the first study to investigate PFC connectivity using fNIRS in ASI. It has the implication of a novel attempt with a practically useful tool to uncover neurobiological differences among Korean adolescents.

A Nationwide Survey on Gastrointestinal Endoscopy Practice Patterns among Pediatric Endoscopists in South Korea / 대한소아소화기영양학회지

Purpose@#Gastrointestinal (GI) endoscopy is an important tool for diagnosing and treating GI diseases in children. This study aimed to analyze the current GI endoscopy practice patterns among South Korean pediatric endoscopists. @*Methods@#Twelve members of the Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition developed a questionnaire. The questionnaire was emailed to pediatric gastroenterologists attending general and tertiary hospitals in South Korea. @*Results@#The response rate was 86.7% (52/60), and 49 of the respondents (94.2%) were currently performing endoscopy. All respondents were performing esophagogastroduodenoscopy, and 43 (87.8%) were performing colonoscopy. Relatively rare procedures for children, such as double-balloon enteroscopy (DBE) (4.1%), endoscopic retrograde cholangiopancreatography (ERCP) (2.0%), and endoscopic ultrasound (EUS) (2.0%), were only performed by pediatric gastroenterologists at very few centers, but were performed by adult endoscopists in most of the centers; of all the respondents, 83.7% (41/49) performed emergency endoscopy. In most centers, the majority of the endoscopies were performed under sedation, with midazolam (100.0%) and ketamine (67.3%) as the most frequently used sedatives. @*Conclusion@#While most pediatric GI endoscopists perform common GI endoscopic procedures, rare procedures, such as DBE, ERCP, and EUS, are only performed by pediatric gastroenterologists at very few centers, and by adult GI endoscopists at most of the centers. For such rare procedures, close communication and cooperation with adult GI endoscopists are required.

Fecal Calprotectin Levels Significantly Correlate with Polyp Size in Children and Adolescents with Juvenile Colorectal Polyps / 대한소아소화기영양학회지

Purpose@#We aimed to investigate factors that correlate with fecal calprotectin (FC) levels in children and adolescents with colorectal polyps. @*Methods@#Pediatric patients aged <19 years who underwent colonoscopic polypectomy for a juvenile polyps (JPs) and FC tests were simultaneously conducted in a multicenter, retrospective study. Baseline demographics, colonoscopic and histological findings, and laboratory tests, including FC levels, were investigated. Correlations between the factors were investigated, and linear regression analysis revealed factors that correlated with FC levels. FC levels measured after polypectomies were investigated and the FC levels pre- and post-polypectomies were compared. @*Results@#A total of 33 patients were included in the study. According to Pearson correlation analysis, the polyp size was the only factor that showed a statistically significant correlation with FC levels (r=0.75, p<0.001). Furthermore, according to the multivariate linear regression analysis, polyp size was the only factor that showed a statistically significant correlation with FC levels (adjusted R2=0.5718, β=73.62, p<0.001). The median FC level was 400 mg/ kg (interquartile range [IQR], 141.6–1,000 mg/kg), and the median polyp size was 14 mm (IQR, 9–20 mm). Nineteen patients underwent post-polypectomy FC tests. FC levels showed a significant decrease after polypectomy from a median of 445.2 mg/kg (IQR, 225–1,000) to 26.5 mg/kg (11.5–51) ( p<0.001). @*Conclusion@#FC levels significantly correlated with polyp size in children and adolescents with JPs.

Comparison of Ablation Performance between Octopus Multipurpose Electrode and Conventional Octopus Electrode

Objective@#To compare Octopus multipurpose (MP) electrodes, which are capable of saline instillation and direct tissue temperature measurement, and conventional electrodes for radiofrequency ablation (RFA) in porcine livers in vivo. @*Materials and Methods@#Sixteen pigs were used in this study. In the first experiment, RFA was performed in the liver for 6 minutes using Octopus MP electrodes (n = 15 ablation zones) and conventional electrodes (n = 12 ablation zones) to investigate the effect of saline instillation. The ablation energy, electrical impedance, and ablation volume of the two electrodes were compared. In the second experiment, RFA was performed near the gallbladder (GB) and colon using Octopus MP electrodes (n = 12 ablation zones for each) with direct tissue temperature monitoring and conventional electrodes (n = 11 ablation zones for each). RFA was discontinued when the temperature increased to > 60°C in the Octopus MP electrode group, whereas RFA was performed for a total of 6 minutes in the conventional electrode group. Thermal injury was assessed and compared between the two groups by pathological examination. @*Results@#In the first experiment, the ablation volume and total energy delivered in the Octopus MP electrode group were significantly larger than those in the conventional electrode group (15.7 ± 4.26 cm3 vs. 12.5 ± 2.14 cm3 , p = 0.027; 5.48 ± 0.49 Kcal vs. 5.04 ± 0.49 Kcal, p = 0.029). In the second experiment, thermal injury to the GB and colon was less frequently noted in the Octopus MP electrode group than that in the conventional electrode group (16.7% [2/12] vs. 90.9% [10/11] for GB and 8.3% [1/12] vs. 90.9% [10/11] for colon, p < 0.001 for all). The total energy delivered around the GB (2.65 ± 1.07 Kcal vs. 5.04 ± 0.66 Kcal) and colon (2.58 ± 0.57 Kcal vs. 5.17 ± 0.90 Kcal) were significantly lower in the Octopus MP electrode group than that in the conventional electrode group (p < 0.001 for all). @*Conclusion@#RFA using the Octopus MP electrodes induced a larger ablation volume and resulted in less thermal injury to the adjacent organs compared with conventional electrodes.

The Association of Smoking Status and Clustering of Obesity and Depression on the Risk of Early–Onset Cardiovascular Disease in Young Adults: A Nationwide Cohort Study

Background and Objectives@#To evaluate the impact of smoking in young adults on the risk of cardiovascular disease (CVD) and the clustering effect of behavioral risk factors such as smoking, obesity, and depression. @*Methods@#A Korean nationwide population-based cohort of a total of 3,280,826 participants aged 20–39 years old who underwent 2 consecutive health examinations were included. They were followed up until the date of CVD (myocardial infarction [MI] or stroke), or December 2018 (median, 6 years). @*Results@#Current smoking, early age of smoking initiation, and smoking intensity were associated with an increased risk of CVD incidence. Even after quitting smoking, the risk of MI was still high in quitters compared with non-smokers. Cigarette smoking, obesity, and depression were independently associated with a 1.3–1.7 times increased risk of CVD, and clustering of 2 or more of these behavioral risk factors was associated with a 2–3 times increased risk of CVD in young adults. @*Conclusions@#In young adults, cigarette smoking was associated with the risk of CVD, and the clustering of 2 or more behavioral risk factors showed an additive risk of CVD.

Family Based Genome-Wide Association Analysis of Schizophrenia in a Korean Population: A Pilot Study / 생물치료정신의학

Objectives@#Schizophrenia (SPR) is the most devastating mental illness that causes severe deterioration in social and occupational functioning, but, the aetiology remains unknown. The aim was to identify patterns of association and segregation for genetic variants and to identify the genes and signalling pathways that determine the risk of developing SPR, through a family-based Genome-wide association study. @*Methods@#We have recruited 27 probands(with SPR) with their parents and siblings whenever possible. DNA was extracted from blood sampling of 58 individuals in 27 families and analysed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test was used to derive SNP association values across all chromosomes. @*Results@#Although none of the final 800,000 SNPs reached the genome-wide significant threshold of 5×10-8 , the most significant 3 SNPs were within the 10-5 -10-7 . @*Conclusions@#This confirms that SPR is not monogenic but results as a consequence of interactions between multiple host genes and possibly also environmental factors. The present approach provides novel insights into the mechanisms underlying SPR and raises the possibility of identifying individuals at risk of acquiring this condition. In this study, several possible susceptibility genes have been identified that are linked to a range of different pathways, which could reflect the mind-body interaction that is included in the psychiatric genomics consortium.