Purpose: This study aimed to assess the impact of aerobic exercise at different intensities over an eight-week period on the expression and activation of cortical synaptic proteins, with the potential to reduce anxiety and improve memory in young mice. Methods: Seven-week-old C57BL/6 mice were subjected to treadmill exercises at low (n = 10), moderate (n = 10), and high intensity (n = 10) for eight weeks. Behavioral assessments were conducted to evaluate anxiety and cognitive function. To explore the underlying mechanisms, we measured the phosphorylated levels of extracellular signal-regulated kinase (ERK), cyclic adenosine monophosphate response-binding protein (CREB), protein kinase (AKT), adenosine monophosphate activated protein kinase (AMPK), synapsin (S9, S549, S609), and PSD-95 in the cortex, as these are associated with synaptic strength. Additionally, the expression of doublecortin (DCX), a neurogenic factor, was analyzed in the hippocampus. Results: Exercise led to reductions in depressive and anxiety-related behaviors and elevated the levels of phosphorylated ERK, CREB, AKT, AMPK, synapsin (S9, S549, S609), and PSD-95 in the cortex of young mice. Furthermore, exercise increased DCX expression in the hippocampus. Moderate-intensity exercise yielded more pronounced effects than other intensities. Conclusion The findings of this research indicate that consistent moderate-intensity exercise increases synaptic strength and reduces depression and anxiety in young mice by activating multiple factors.

Background: The ionic mechanism underlying Brugada syndrome (BrS) arises from an imbalance in transient outward current flow between the epicardium and endocardium.Previous studies report that artemisinin, originally derived from a Chinese herb for antimalarial use, inhibits the Ito current in canines. In a prior study, we showed the antiarrhythmic effects of artemisinin in BrS wedge preparation models. However, quinidine remains a well-established antiarrhythmic agent for treating BrS. Therefore, this study aims to investigate the efficacy of combining artemisinin with low-dose quinidine in suppressing ventricular tachyarrhythmia (VTA) in experimental canine BrS models. Methods: Transmural pseudo-electrocardiogram and epicardial/endocardial action potential (AP) were recorded from coronary-perfused canine right ventricular wedge preparation. To mimic the BrS model, acetylcholine (3 μM), calcium channel blocker verapamil (1 μM), and Ito agonist NS5806 (6–10 μM) were administered until VTA was induced. Subsequently, lowdose quinidine (1–2 μM) combined with artemisinin (100 μM) was perfused to mitigate VTA.Key parameters, including AP duration, J wave area, notch index, and T wave dispersion, were measured. Results: After administering the provocation agents, all sample models exhibited prominent J waves and VTA. Artemisinin alone (100–150 μM) suppressed VTA and restored the AP dome in all three preparations. Its infusion resulted in reductions in the J wave area and epicardial notch index. Consequently, low-dose quinidine (1–2 μM) did not fully restore the AP dome in all six sample models. However, when combined with additional artemisinin (100 μM), lowdose quinidine effectively suppressed VTA in all six models and restored the AP dome while also decreasing the J wave area and epicardial notch index. Conclusion Low-dose quinidine alone fails to fully alleviate VTA in the BrS wedge model.However, its combination with artemisinin effectively suppresses VTA. Artemisinin may reduce the therapeutic dose of quinidine, potentially minimizing its associated adverse effects.

Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

Background: Currently, little is known about the relationship between the temporal radiographic latent trajectories, which are based on the extent of coronavirus disease 2019 (COVID-19) pneumonia and clinical outcomes. This study aimed to elucidate the differences in the temporal trends of critical laboratory biomarkers, utilization of critical care support, and clinical outcomes according to temporal radiographic latent trajectories. Methods: We enrolled 2,385 patients who were hospitalized with COVID-19 and underwent serial chest radiographs from December 2019 to March 2022. The extent of radiographic pneumonia was quantified as a percentage using a previously developed deep-learning algorithm. A latent class growth model was used to identify the trajectories of the longitudinal changes of COVID-19 pneumonia extents during hospitalization. We investigated the differences in the temporal trends of critical laboratory biomarkers among the temporal radiographic trajectory groups. Cox regression analyses were conducted to investigate differences in the utilization of critical care supports and clinical outcomes among the temporal radiographic trajectory groups. Results: The mean age of the enrolled patients was 58.0 ± 16.9 years old, with 1,149 (48.2%) being male. Radiographic pneumonia trajectories were classified into three groups: The steady group (n = 1,925, 80.7%) exhibited stable minimal pneumonia, the downhill group (n = 135, 5.7%) exhibited initial worsening followed by improving pneumonia, and the uphill group (n = 325, 13.6%) exhibited progressive deterioration of pneumonia. There were distinct differences in the patterns of temporal blood urea nitrogen (BUN) and C-reactive protein (CRP) levels between the uphill group and the other two groups. Cox regression analyses revealed that the hazard ratios (HRs) for the need for critical care support and the risk of intensive care unit admission were significantly higher in both the downhill and uphill groups compared to the steady group. However, regarding in-hospital mortality, only the uphill group demonstrated a significantly higher risk than the steady group (HR, 8.2; 95% confidence interval, 3.08–21.98). Conclusion Stratified pneumonia trajectories, identified through serial chest radiographs, are linked to different patterns of temporal changes in BUN and CRP levels. These changes can predict the need for critical care support and clinical outcomes in COVID-19 pneumonia.Appropriate therapeutic strategies should be tailored based on these disease trajectories.

This study aimed to assess the utilization trends of pulmonary rehabilitation (PR) among lung cancer patients in Korea using the National Health Insurance Service (NHIS) database (2017 to 2021). PR was introduced and covered under the NHIS in 2016, primarily for chronic obstructive pulmonary disease, but recent evidence suggests its benefits for lung cancer patients. Data extraction was based on Korea Informative Classification of Diseases 8th revision codes C33 and C34, with PR prescriptions identified by codes MM440 and MM290.Descriptive statistical analysis was performed, and propensity score matching was used for comparison between PR and non-PR groups. Results showed a significant increase in PR utilization, with the number of patients receiving PR (MM440) rising from 1,002 in 2017 to 3,723 in 2021, indicating a 3.7-fold increase. However, the proportion of patients receiving PR remained low at 2.9% in 2021. Enhanced access to PR services and improved evaluation strategies are essential for optimizing patient outcomes.

Background: Tinnitus is a bothersome condition associated with various mechanisms of action. Although treatment methods vary according to these mechanisms, standardized guidelines would benefit both patients and clinicians. We conducted a Delphi study, a method that collects expert opinions through multiple rounds of questionnaires, to reach a consensus on tinnitus treatment with professional experts. Methods: A two-round modified Delphi survey was conducted to develop a clinical consensus on tinnitus treatment. The experts scored each statement on a scale of 1 (highest disagreement) to 9 (highest agreement) for their level of agreement on tinnitus treatment.Consensus was defined when 75% or more of the participants scored 7–9, and 15% or less scored 1–3. To ensure reliability of the responses, the content validity ratio and Kendall’s coefficient of concordance were evaluated. Results: Approximately 19 of 31 statements reached a consensus. All 3 statements reached a consensus regarding the candidates for treatment. Regarding treatment, 3 of 8 statements on medication, 2 of 2 statements on tinnitus retraining therapy/cognitive behavioral therapy, and 5 of 7 statements on auditory rehabilitation reached a positive consensus. Although all 6 statements regarding miscellaneous treatment reached a consensus, most were negatively agreed. For treatment with neuromodulation, none of the 5 statements reached a consensus. Conclusion The experts reached a high level of consensus on treatment candidates, tinnitus retraining therapy/cognitive behavioral therapy, and auditory rehabilitation in this modified Delphi study. The results of this study can provide beneficial and practical information for clinicians regarding the treatment of tinnitus.

Background: s/Aims: Hepatocellular carcinoma (HCC) is the sixth most common cancer and second leading cause of cancer-related deaths in South Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2016-2018. Methods: Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative database of patients newly diagnosed with HCC in South Korea, were analyzed. This study investigated 4,462 patients with HCC registered in the KPLCR in 2016-2018. Results: The median patient age was 63 years (interquartile range, 55-72). 79.7% of patients were male. Hepatitis B infection was the most common underlying liver disease (54.5%). The Barcelona Clinic Liver Cancer (BCLC) staging system classified patients as follows: stage 0 (14.9%), A (28.8%), B (7.5%), C (39.0%), and D (9.8%). The median overall survival was 3.72 years (95% confidence interval, 3.47-4.14), with 1-, 3-, and 5-year overall survival rates of 71.3%, 54.1%, and 44.3%, respectively. In 2016-2018, there was a significant shift toward BCLC stage 0-A and Child-Turcotte-Pugh liver function class A (P<0.05), although survival rates did not differ by diagnosis year. In the treatment group (n=4,389), the most common initial treatments were transarterial therapy (31.7%), surgical resection (24.9%), best supportive care (18.9%), and local ablation therapy (10.5%). Conclusions Between 2016 and 2018, HCC tended to be diagnosed at earlier stages, with better liver function in later years. However, since approximately half of the patients remained diagnosed at an advanced stage, more rigorous and optimized HCC screening strategies should be implemented.

Background: s/Aims: Radiofrequency ablation (RFA) is widely employed for managing recurrent hepatocellular carcinoma (HCC) following transarterial chemoembolization (TACE). However, local tumor progression (LTP) after treatment remains a significant challenge. This study evaluates the efficacy of saline-perfused bipolar RFA using twin internally cooled-perfusion (TICP) electrodes in managing recurrent HCC post-TACE. Methods: Between September 2017 and January 2019, 100 patients with 105 nodules (mean diameter, 1.6±0.5 cm) were prospectively enrolled. Bipolar RFA with TICP electrodes was performed under ultrasound-computed tomography/magnetic resonance fusion guidance. The primary outcome was the 2-year cumulative incidence of LTP. Results: The technical success and technique efficacy rates were 100% and 97%, respectively. During a median follow-up period of 34.0 months (range, 3-41), the estimated LTP rates were 13.3% at 1 year and 17.7% at 2 years. Progression-free survival rates were 37.8% and 27.7% at 1 year and 2 years, respectively. Conclusions Saline-perfused bipolar RFA using TICP electrodes demonstrates promising results for recurrent HCC after TACE, achieving high technical success and effective local tumor control rates.

Irritable bowel syndrome (IBS) is a chronic, disabling, and functional bowel disorder that significantly affects social functioning and reduces quality of life and increases social costs. The Korean Society of Neurogastroenterology and Motility published clinical practice guidelines on the management of IBS based on a systematic review of the literature in 2017, and planned to revise these guidelines in light of new evidence on the pathophysiology, diagnosis, and management of IBS. The current revised version of the guidelines is consistent with the previous version and targets adults diagnosed with or suspected of having IBS. These guidelines were developed using a combination of de novo and adaptation methods, with analyses of existing guidelines and discussions within the committee, leading to the identification of key clinical questions. Finally, the guidelines consisted of 22 recommendations, including 3 concerning the definition and risk factors of IBS, 4 regarding diagnostic modalities and strategies, 2 regarding general management, and 13 regarding medical treatment. For each statement, the advantages, disadvantages, and precautions were thoroughly detailed. The modified Delphi method was used to achieve expert consensus to adopt the core recommendations of the guidelines. These guidelines serve as a reference for clinicians (including primary care physicians, general healthcare providers, medical students, residents, and other healthcare professionals) and patients, helping them to make informed decisions regarding IBS management.