Phloroglucinol Derivatives Exert Anti-Inflammatory Effects and Attenuate Cognitive Impairment in LPS-Induced Mouse Model.

Neuroinflammation is an inflammatory immune response that arises in the central nervous system. It is one of the primary causes of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Phloroglucinol (PG) is a natural product contained in extracts of plant, algae and microbe and has been reported to have antioxidant and anti-inflammatory properties. In this study, we synthesized PG derivatives to enhance antioxidant and anti-inflammatory activity. Among PG derivatives, 6 a suppressed pro-oxidative and inflammatory molecule nitric oxide (NO) production more effectively than PG. Moreover, 6 a dose-dependently reduced the expression of proinflammatory cytokines such as IL-6, IL-1ß, TNF-α, and NO producing enzyme iNOS in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Additionally, we confirmed that 6 a alleviated cognitive impairment and glial activation in mouse model of LPS-induced neuroinflammation. These findings suggest that novel PG derivative, 6 a, is a potential treatment for neurodegenerative diseases.

Prediction of postoperative cerebral infarction after combined bypass surgery in adult moyamoya disease: combining quantitative parameters on RAPID perfusion CT with clinically related factors.

OBJECTIVE: The aim of this study was to identify predictive factors of postoperative cerebral infarction (PostCI) following combined bypass (CB) surgery in adult patients with moyamoya disease (MMD) using quantitative parameters from the rapid processing of perfusion and diffusion (RAPID) perfusion CT (PCT) software. METHODS: The authors retrospectively reviewed 276 total hemispheres in patients with MMD who underwent CB. Preoperative volumes of time-to-maximum (Tmax) > 4 sec and > 6 sec were obtained from the RAPID analysis of PCT. These quantitative parameters, along with other clinical and angiographic factors, were statistically analyzed to determine the significant predictors for PostCI following CB. RESULTS: PostCI occurred in 17 hemispheres (6.16%). PCA involvement (p = 0.016), and the volume of Tmax > 6 sec (p < 0.001) and Tmax > 4 sec (p < 0.001), were identified as variables related to PostCI in the univariable analysis. In the multivariable analysis, the volume of Tmax > 6 sec (OR 1.013, 95% confidence interval 1.007-1.019, p < 0.001) was determined to be an independent predictive factor significantly associated with PostCI after CB in adult patients with MMD. In the receiver operating characteristic (ROC) curve, the cutoff value of the preoperative volume of Tmax > 6 sec was determined to be 59.5 ml (sensitivity 82.4%, specificity 71.9%, area under the ROC curve 0.811). CONCLUSIONS: For adult patients with MMD and a large volume of Tmax > 6 sec over 59.5 ml, more caution is required when deciding to undergo bypass surgery and in postoperative management.

Development and validation of a prediction model for evaluating extubation readiness in preterm infants.

Successful early extubation has advantages not only in terms of short-term respiratory morbidities and survival but also in terms of long-term neurodevelopmental outcomes in preterm infants. However, no consensus exists regarding the optimal protocol or guidelines for extubation readiness in preterm infants. Therefore, the decision to extubate preterm infants was almost entirely at the attending physician's discretion. We identified robust and quantitative predictors of success or failure of the first planned extubation attempt before 36 weeks of post-menstrual age in preterm infants (<32 weeks gestational age) and developed a prediction model for evaluating extubation readiness using these predictors. Extubation success was defined as the absence of reintubation within 72 h after extubation. This observational cohort study used data from preterm infants admitted to the neonatal intensive care unit of Seoul National University Bundang Hospital in South Korea between July 2003 and June 2019 to identify predictors and develop and test a predictive model for extubation readiness. Data from preterm infants included in the Medical Informative Medicine for Intensive Care (MIMIC-III) database between 2001 and 2008 were used for external validation. From a machine learning model using predictors such as demographics, periodic vital signs, ventilator settings, and respiratory indices, the area under the receiver operating characteristic curve and average precision of our model were 0.805 (95% confidence interval [CI], 0.802-0.809) and 0.917, respectively in the internal validation and 0.715 (95% CI, 0.713-0.717) and 0.838, respectively in the external validation. Our prediction model (NExt-Predictor) demonstrated high performance in assessing extubation readiness in both internal and external validations.

Effective Timing of Introducing an Inpatient Smoking Cessation Program to Cancer Patients

Purpose@#We aimed to identify factors influencing smoking cessation success among cancer patients registered in an inpatient smoking cessation program at a single cancer center. @*Materials and Methods@#The electronic medical records of enrolled patients with solid cancer were retrospectively reviewed. We evaluated factors associated with 6-month smoking cessation. @*Results@#A total of 458 patients with cancer were included in this study. Their mean age was 62.9±10.3 years, and 56.3% of the participants had lung cancer. 193 (42.1%) had not yet begun their main treatment. The mean number of counseling sessions for the participants was 8.4±3.5, and 46 (10.0%) patients were prescribed smoking cessation medications. The 6-month smoking cessation success rate was 48.0%. Multivariate analysis showed that younger age (<65 years), cohabited status, early stage, and the number of counseling sessions were statistically significant factors affecting 6-month smoking cessation success (p<0.05). Initiation of a cessation program before cancer treatment was significantly associated with cessation success (odds ratio, 1.66; 95% confidence interval, 1.02–2.70; p=0.040). @*Conclusion@#Smoking cessation intervention must be considered when establishing a treatment plan immediately after a cancer diagnosis among smokers.

The Impact of Slow Infusion Intermittent Feeding on Gavage Feeding-Associated Cardiorespiratory Deterioration in Neonatal Intensive Care Unit Infants

Purpose@#Infants in the neonatal intensive care unit (NICU) often show cardiorespiratory deterioration during gavage feeding. We aimed to determine whether slow infusion intermittent feeding (SIIF) can reduce respiratory deterioration during gavage feeding in preterm infants in the NICU. @*Methods@#Data on preterm infants whose gavage feeding method was changed to SIIF (1-­­hour infusion with an infusion pump and 2-­hour rest within a 3­-hour interval) from bolus gravity feeding (2-­ or 3-­hour interval) due to feeding­-associated cardiorespiratory deterioration were retrospectively reviewed. A significant cardiorespiratory event was defined as a saturation level below 80% or heart rate below 80 bpm. We compared the frequency of cardiorespiratory events and the level of respiratory support 24 hours before and after the application of SIIF. @*Results@#A total of 34 infants were enrolled and analyzed. The total frequency of desaturation or bradycardia significantly decreased after SIIF application (8.94 vs. 5.03, P=0.001). The frequency of feeding-­related bradycardia and desaturation also significantly decreased (4.15 vs. 1.68, P=0.008). Out of 34 patients, 11 (32.4%) had a decreased level of ventilator support within 1 day after SIIF. The respiratory severity scores of the 10 patients who received invasive ventilator support decreased significantly after SIIF (5.24 vs. 4.59, P=0.032). @*Conclusion@#SIIF significantly decreased gavage feeding­-associated cardiorespiratory events and reduced respiratory support in approximately one-­third of subjects. Therefore, SIIF may be a therapeutic option for gavage feed-­associated respiratory deterioration in preterm infants in the NICU.

Comparison between Placement of an Amniotic Membrane Contact Lens and Temporary Amniotic Membrane Transplantation

Purpose@#We compared the clinical utilities of an amniotic contact lens and temporary amniotic membrane transplantation in patients with persistent corneal epithelial defects. @*Methods@#Patients diagnosed with persistent corneal epithelial defects from November 2019 to July 2022 were randomly assigned to either lens placement for 2 weeks or temporary transplantation for 1 week, and the outcomes were retrospectively analyzed. The best-corrected visual acuity, corneal sensation, tear film break-up time, and corneal opacity were measured before and after the interventions. The treatment success rates, recurrences, and other complications were analyzed during the follow-up period. @*Results@#We placed lenses in 32 patients (32 eyes) and 20 patients (20 eyes) underwent transplantation. In both groups, significant differences in best-corrected visual acuity, corneal sensation, tear film break-up time, and corneal opacity were apparent after intervention vs. before. None of the parameters showed any significant differences in terms of their rates of change. @*Conclusions@#In patients with persistent corneal epithelial defects, amniotic contact lens placement is an effective outpatient procedure and is not inferior to temporary amniotic membrane transplantation.

Outcomes of Endoscopic Tympanoplasty for Large Perforations: A Multicenter Retrospective Study in South Korea

Objectives@#. Endoscopic tympanoplasty (ET) provides minimally invasive transcanal access to the middle ear and improves middle ear visibility for the treatment of tympanic membrane (TM) perforations. However, the literature on surgical outcomes for large TM perforations is lacking and limited to small series. This study aimed to evaluate the clinical benefits of ET for large TM perforations. @*Methods@#. This retrospective cohort study was conducted at nine tertiary referral hospitals in South Korea, where 252 patients who underwent ET as primary surgery from September 2019 to August 2021 were included. The outcome measures included the graft success rate and pre- and postoperative audiometric data. @*Results@#. In 239 patients, the graft success rate of ET for large or subtotal perforations was 86.2% (206 patients), while the graft failure rate was 13.8% (33 patients). The graft failure rate was directly correlated with surgical techniques, including overlay and medial or lateral underlay tympanoplasty (P=0.027). Lateral underlay tympanoplasty showed the most favorable results. Sex, laterality, etiology, site and size of perforation, operation time, and graft materials did not vary significantly between the graft success and failure groups (P>0.05). The mean air-bone gap (ABG) improved significantly in both groups (graft success group: 10.0±0.6 dB and graft failure group: 7.7±0.3 dB; P<0.001). However, the ABG improvement did not significantly differ between the groups. Analysis of covariance revealed that the postoperative 500-Hz bone conduction threshold improved after successful ET (adjusted coefficient, –11.351; 95% confidence interval, –21.491 to –1.212; P=0.028). @*Conclusion@#. This study involved the largest population to date of large TM perforations treated by ET. The study findings suggest that ET is feasible and effective in treating large TM perforations.

High Mean Platelet Volume Is Associated with Cerebral White Matter Hyperintensities in Non-Stroke Individuals

Purpose@#The mean platelet volume (MPV) is regarded as a marker for thrombosis, atherosclerosis, and inflammation in various vascular diseases. However, it still remains unclear whether plasma MPV is associated with cerebral white matter hyperintensities (WMH) and cerebral microvascular pathology in the elderly population. @*Materials and Methods@#We examined whether MPV level is associated with the presence of cerebral WMH on brain magnetic resonance imaging from 870 non-stroke outpatient subjects. The subjects were divided into three groups according to the consecutive level of MPV (low T1, middle T2, and high T3 MPV tertile groups). To determine the association of MPV levels with the WMH, logistic regression and receiver operating characteristic curve analyses were conducted. @*Results@#Subjects with higher MPV level were older and more likely to have hypertension, diabetes mellitus, and low renal function. Cerebral WMH were more prevalent in subjects with higher MPV level. After adjusting for confounding factors, moderate to severe cerebral WMH were significantly associated with high MPV tertile level. This association remained significant after adjusting for other cerebral vascular pathologies. T2 [odds ratio (OR): 1.49, 95% confidence interval (CI): 1.03–2.15] and T3 MPV tertile groups (OR: 1.51, 95%CI: 1.04–2.20) had more cerebral WMH lesions compared to T1 MPV tertile group. In addition, the subjects with higher Fazekas scores showed higher MPV level (p=0.020). @*Conclusion@#We found that high MPV level is independently associated with cerebral WMH. This result suggests that platelet activation plays a role in the development of cerebral WMH.

Clinical Outcomes of Moderately Hypofractionated Concurrent Chemoradiotherapy for Newly Diagnosed Glioblastoma

Purpose@#Hypofractionated radiotherapy (HypoRT) has recently been implemented in patients with glioblastoma (GBM) receiving concurrent temozolomide. Lymphopenia during treatment (LDT) is considered an important prognostic factor of clinical outcomes for GBM. We aimed to investigate the outcomes of HypoRT. @*Materials and Methods@#Among 223 patients with GBM, 145 and 78 were treated with conventionally fractionated RT (ConvRT, 60 Gy in 30 fractions) and HypoRT (58.5 Gy in 25 fractions), respectively. To balance characteristics between the two groups, propensity score matching (PSM) was performed. @*Results@#Patients in the HypoRT group were older and had smaller tumors than those in the ConvRT group (p0.05). Multivariable analysis before PSM revealed that ≥grade 2 LDT at 6 months was associated with inferior outcomes. Subsequent analysis demonstrated that HypoRT significantly reduced the rate of ≥grade 2 LDT at 6 months post-RT before and after PSM. @*Conclusion@#HypoRT with 58.5 Gy in 25 fractions could provide comparable oncologic outcomes and significantly reduce the ALC changes. In addition, HypoRT decreased the LDT. Further investigation should be warranted to suggest the significance of reduced LDT through HypoRT affecting survival outcomes.

The prognostic value of comprehensive geriatric assessment on the management of older patients with small cell lung cancer

Background/Aims@#The prognostic value of a comprehensive geriatric assessment (CGA) for the management of older small cell lung cancer (SCLC) patients remains to be established. @*Methods@#A retrospective cohort enrolled 21 SCLC patients over 65 years from March 2018 to 2019 at the Yonsei Cancer Center. The CGA included the following instruments: frailty, body mass index, sarcopenia (circumference of arm and calf, Timed Up and Go test, grip strength), comorbidity, polypharmacy, activities of daily living (ADL), Instrumental ADL, nutrition, depression, and cognitive function. The correlations of oncological and geriatric variables with overall survival (OS) were determined. The log-rank test with Cox model and Kaplan-Meier method were used for the analysis. @*Results@#The median age was 75 years (range, 67 to 85). All patients had the Eastern Cooperative Oncology Group performance status 0–2. The median survival was 9.93 months (range, 1.53 to 36.30). Among CGA parameters, ADL and nutritional status had significant differences in OS in univariate analysis. In multivariate analysis, only nutritional status was independently associated with survival (hazard ratio, 0.17; 95% confidence interval, 0.05 to 0.57). Median OS for low nutritional status was 5.63 months and the normal nutrition group was 15.5 months (p = 0.004). @*Conclusions@#Pre-treatment nutritional status measured by CGA appears to be a predictor of OS in older SCLC patients. However, for further generalization of the implication of CGA in SCLC, a larger scale study with prospective design is strongly needed.

Current Status and Key Issues of Data Management in Tertiary Hospitals: A Case Study of Seoul National University Hospital / 대한의료정보학회지

Objectives@#In the era of the Fourth Industrial Revolution, where an ecosystem is being developed to enhance the quality of healthcare services by applying information and communication technologies, systematic and sustainable data management is essential for medical institutions. In this study, we assessed the data management status and emerging concerns of three medical institutions, while also examining future directions for seamless data management. @*Methods@#To evaluate the data management status, we examined data types, capacities, infrastructure, backup methods, and related organizations. We also discussed challenges, such as resource and infrastructure issues, problems related to government regulations, and considerations for future data management. @*Results@#Hospitals are grappling with the increasing data storage space and a shortage of management personnel due to costs and project termination, which necessitates countermeasures and support. Data management regulations on the destruction or maintenance of medical records are needed, and institutional consideration for secondary utilization such as long-term treatment or research is required. Government-level guidelines for facilitating hospital data sharing and mobile patient services should be developed. Additionally, hospital executives at the organizational level need to make efforts to facilitate the clinical validation of artificial intelligence software. @*Conclusions@#This analysis of the current status and emerging issues of data management reveals potential solutions and sets the stage for future organizational and policy directions. If medical big data is systematically managed, accumulated over time, and strategically monetized, it has the potential to create new value.

Effects of Particulate Matter Exposure on the Eustachian Tube and Middle Ear Mucosa of Rats

Objectives@#. Particulate matter (PM) is a risk factor for various diseases. Recent studies have established an association between otitis media (OM) and PM exposure. To confirm this relationship, we developed a novel exposure model designed to control the concentration of PM, and we observed the effects of PM exposure on the Eustachian tube (ET) and middle ear mucosa of rats. @*Methods@#. Forty healthy, 10-week-old, male Sprague-Dawley rats were divided into 3-day, 7-day, 14-day exposure, and control groups (each, n=10). The rats were exposed to incense smoke as the PM source for 3 hours per day. After exposure, bilateral ETs and mastoid bullae were harvested, and histopathological findings were compared using microscopy and transmission electron microscopy (TEM). The expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α, and vascular endothelial growth factor (VEGF) in the middle ear mucosa of each group were compared using real-time reverse transcription polymerase chain reaction (RT-PCR). @*Results@#. In the ET mucosa of the exposure group, the goblet cell count significantly increased after PM exposure (P=0.032). In the middle ear mucosa, subepithelial space thickening, increased angio-capillary tissue, and inflammatory cell infiltration were observed. Moreover, the thickness of the middle ear mucosa in the exposure groups increased compared to the control group (P<0.01). The TEM findings showed PM particles on the surface of the ET and middle ear mucosa, and RT-PCR revealed that messenger RNA (mRNA) expression of IL-1β significantly increased in the 3-day and 7-day exposure groups compared to the control group (P=0.035). VEGF expression significantly increased in the 7-day exposure group compared to the control and 3-day exposure groups (P<0.01). @*Conclusion@#. The ET and middle ear mucosa of rats showed histopathologic changes after acute exposure to PM that directly reached the ET and middle ear mucosa. Therefore, acute exposure to PM may play a role in the development of OM.

Intensified First Cycle of Rituximab Plus Eight Cycles of Cyclophosphamide, Doxorubicin, Vincristine, and Prednisolone with Rituximab Chemotherapy for Advanced-Stage or Bulky Diffuse Large B-Cell Lymphoma: A Multicenter Phase II Consortium for Improving Survival of Lymphoma (CISL) Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). @*Materials and Methods@#Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. @*Results@#Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). @*Conclusion@#Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Recommendation Using the Delphi Method (Version 2023.1)

Background@#During the coronavirus disease 2019 (COVID-19) pandemic, the need for appropriate treatment guidelines for patients with brain tumors was indispensable due to the lack and limitations of medical resources. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. @*Methods@#The KSNO Guideline Working Group was composed of 22 multidisciplinary experts on neuro-oncology in Korea. In order to reach consensus among the experts, the Delphi method was used to build up the final recommendations. @*Results@#All participating experts completed the series of surveys, and the results of final survey were used to draft the current consensus recommendations. Priority levels of surgery and radiotherapy during crises were proposed using appropriate time window-based criteria for management outcome. The highest priority for surgery is assigned to patients who are life-threatening or have a risk of significant impact on a patient’s prognosis unless immediate intervention is given within 24–48 hours. As for the radiotherapy, patients who are at risk of compromising their overall survival or neurological status within 4–6 weeks are assigned to the highest priority. Curative-intent chemotherapy has the highest priority, followed by neoadjuvant/adjuvant and palliative chemotherapy during a crisis period. Telemedicine should be actively considered as a management tool for brain tumor patients during the mass infection crises such as the COVID-19 pandemic. @*Conclusion@#It is crucial that adequate medical care for patients with brain tumors is maintained and provided, even during times of crisis. This guideline will serve as a valuable resource, assisting in the delivery of treatment to brain tumor patients in the event of any future crisis.

The Korean Society for Neuro-Oncology (KSNO) Guideline for the Management of Brain Tumor Patients During the Crisis Period: A Consensus Survey About Specific Clinical Scenarios (Version 2023.1)

Background@#During the coronavirus disease 2019 (COVID-19) pandemic, there was a shortage of medical resources and the need for proper treatment guidelines for brain tumor patients became more pressing. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has undertaken efforts to develop a guideline that is tailored to the domestic situation and that can be used in similar crisis situations in the future. As part II of the guideline, this consensus survey is to suggest management options in specific clinical scenarios during the crisis period. @*Methods@#The KSNO Guideline Working Group consisted of 22 multidisciplinary experts on neuro-oncology in Korea. In order to confirm a consensus reached by the experts, opinions on 5 specific clinical scenarios about the management of brain tumor patients during the crisis period were devised and asked. To build-up the consensus process, Delphi method was employed. @*Results@#The summary of the final consensus from each scenario are as follows. For patients with newly diagnosed astrocytoma with isocitrate dehydrogenase (IDH)-mutant and oligodendroglioma with IDH-mutant/1p19q codeleted, observation was preferred for patients with low-risk, World Health Organization (WHO) grade 2, and Karnofsky Performance Scale (KPS) ≥60, while adjuvant radiotherapy alone was preferred for patients with high-risk, WHO grade 2, and KPS ≥60. For newly diagnosed patients with glioblastoma, the most preferred adjuvant treatment strategy after surgery was radiotherapy plus temozolomide except for patients aged ≥70 years with KPS of 60 and unmethylated MGMT promoters. In patients with symptomatic brain metastasis, the preferred treatment differed according to the number of brain metastasis and performance status. For patients with newly diagnosed atypical meningioma, adjuvant radiation was deferred in patients with older age, poor performance status, complete resection, or low mitotic count. @*Conclusion@#It is imperative that proper medical care for brain tumor patients be sustained and provided, even during the crisis period. The findings of this consensus survey will be a useful reference in determining appropriate treatment options for brain tumor patients in the specific clinical scenarios covered by the survey during the future crisis.

Improved Muscle Mass and Function With Protein Supplementation in Older Adults With Sarcopenia: A Meta-Analysis

Objective@#To systematically review the effects of protein supplementation in older adults with sarcopenia. @*Methods@#A systematic literature search was conducted in PubMed, Cochrane Library, and Embase databases until May 2023. The inclusion criteria were as follows: (1) randomized controlled trials with a quantitative study design; (2) studies with a study group of older adults with sarcopenia; (3) studies comparing muscle mass, muscle strength, and performance of older adults with sarcopenia after protein supplementation; and (4) studies published up to May 2023. @*Results@#Six retrospective comparative studies, including 715 patients, met the inclusion criteria. The nutritional supplementation group exhibited significant improvement in appendicular skeletal muscle mass (standardized mean difference [SMD]=0.41; 95% confidence interval [CI], 0.24–0.58; p<0.001; I2=1%), while handgrip strength (SMD=0.37; 95% CI, -0.32–1.07; p=0.29; I2=94%) and Short Physical Performance Battery (SPPB) (SMD=0.35; 95% CI, -0.47–1.18; p=0.40; I2=94%) showed a tendency for improvement. @*Conclusion@#Nutritional supplementation with protein increased appendicular muscle mass in older adults with sarcopenia and improved handgrip strength and SPPB scores.

Identification and overcoming rituximab resistance in diffuse large B-cell lymphoma using next-generation sequencing

Background/Aims@#Although rituximab, an antiCD20 monoclonal antibody, has dramatically improved the clinical outcomes of diffuse large B-cell lymphoma, rituximab resistance remains a challenge. @*Methods@#We developed a rituximab-resistant cell line (RRCL) by sequential exposure to gradually increasing concentrations of rituximab in a rituximab-sensitive cell line (RSCL). When the same dose of rituximab was administered, RRCL showed a smaller decrease in cell viability and apoptosis than RSCL. To determine the differences in gene expression between RSCL and RRCL, we performed next-generation sequencing. @*Results@#In total, 1,879 differentially expressed genes were identified, and in the over-representation analysis of Consensus-PathDB, mitogen-activated protein kinase (MAPK) signaling pathway showed statistical significance. MAPK13, which encodes the p38δ protein, was expressed more than four-fold in RRCL. Western blot analysis revealed that phosphop38 expression mainwas increased in RRCL, and when p38 inhibitor was administered, phosphop38 expression was significantly decreased. Therefore, we hypothesized that p38 MAPK activation was associated with rituximab resistance. Previous studies have suggested that p38 is associated with NF-κB activation. Deferasirox has been reported to inhibit NF-κB activity and suppress phosphorylation of the MAPK pathway. Furthermore, it also has cytotoxic effects on various cancers and synergistic effects in overcoming drug resistance. In this study, we confirmed that deferasirox induced dose-dependent cytotoxicity in both RSCL and RRCL, and the combination of deferasirox and rituximab showed a synergistic effect in RRCL at all combination concentrations. @*Conclusions@#We suggest that p38 MAPK, especially p38δ, activation is associated with rituximab resistance, and deferasirox may be a candidate to overcome rituximab resistance.

Periodic Limb Movement Disorder and Mortality / 수면정신생리

Periodic limb movement disorder (PLMD) is a sleep-related movement disorder characterized by involuntary, rhythmic limb movements during sleep. While PLMD itself is not considered life-threatening, its association with certain underlying health conditions raises concerns about mortality risks. PLMD has been found to be associated with cardiovascular diseases such as hypertension and cardiovascular disease. The fragmented sleep caused by the repetitive limb movements and associated arousals may contribute to sympathetic activation, chronic sleep disruption, sleep deprivation, and subsequent cardiovascular problems, which can increase mortality risks. The comorbidities and health factors commonly associated with PLMD, such as obesity, diabetes, and chronic kidney disease, may also contribute to increased mortality risks. PLMD is often observed alongside other neurological disorders, including restless legs syndrome (RLS) and Parkinson's disease. The presence of PLMD in these conditions may exacerbate the underlying health issues and potentially contribute to higher mortality rates. Further research is needed to elucidate the specific mechanisms linking PLMD to mortality risks and to develop targeted interventions that address these risks.

Dietary Carotene Intake and Suicidal Ideation in Korean Females: Analysis of Data From the Korea National Health and Nutrition Examination Survey (2012, 2013, and 2015)

Objective@#The suicide rate in Korea was the highest among countries in the Organisation for Economic Co-operation and Development in 2019. In a previous study, higher intake of vegetables and fruits was associated with a lower risk of suicidal ideation, and carotene-rich fruits and vegetables lowered the risk of depression. This study aimed to examine the direct relationship between carotene intake and suicidal ideation, adjusting for the effect on depression. @*Methods@#This study used data from the Korea National Health and Nutrition Examination Survey (KNHANES) conducted in 2012, 2013, and 2015. Carotene intake was assessed through a food intake frequency survey with a 24-hour recall. Suicidal ideation and depression were assessed using the mental health section of the KNHANES. We applied logistic regression to assess the relationship between carotene intake and suicidal ideation, adjusting for potential confounders. @*Results@#A total of 5,480 females aged 19–64 years were included in this study. Carotene intake was significantly lower in the suicidal ideation group (3,034.5±1,756.4 μg/day) than in the nonsuicidal ideation group (3,225.4±1,795.1 μg/day) (p=0.015). We found a significant inverse association between carotene intake and the risk of suicidal ideation after adjusting for potential confounders (odds ratio=0.934, 95% confidence interval=0.873–0.999). @*Conclusion@#These results suggest that carotene intake may be inversely associated with the risk of suicidal ideation. Our findings may inform the development of new nutritional interventions to prevent increases in the risk of suicide worldwide.

The Factors Affecting Longitudinal Course of Posttraumatic Stress Disorder Symptoms in Sexual Assault Victims

Objective@#This study aimed to identify the factors affecting posttraumatic stress disorder (PTSD) symptom remission prospectively through a 1-year follow-up of sexual assault (SA) victims. @*Methods@#A total 65 female SA victims who visited the crisis intervention center were included. Self-administered questionnaires regarding PTSD symptoms and PTSD related prognostic factors were conducted at both recruitment (T1) and 1 year after recruitment (T2). The multivariate analyses were used to determine the significant predictors of PTSD remissionon-remission state 1 year after SA. @*Results@#In logistic regression analysis, both anxiety and secondary victimization were identified as significant factors explaining the results on PTSD remissionon-remission state at T2 (Beck’s Anxiety Inventory [BAI], p=0.003; Secondary Victimization Questionnaire, p=0.024). In a linear mixed analysis, both depression and anxiety were found to be significant variables leading to changes in Posttraumatic Diagnostic Scale for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition from T1 to T2 (BAI, p<0.001; Center for Epidemiological Studies Depression Scale, p<0.001). @*Conclusion@#Depression, anxiety symptoms, and secondary victimization after SA were associated with PTSD symptom non-remission 1 year after SA.