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Preclinical models suggest anticancer activity of IM156, a novel biguanide mitochondrial protein complex 1 inhibitor of oxidative phosphorylation (OXPHOS). This first-in-human dose-escalation study enrolled patients with refractory advanced solid tumors to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D). Eligible patients received oral IM156 every other day (QOD) or daily (QD) and were assessed for safety, dose-limiting toxicities (DLTs), pharmacokinetics, and preliminary signals of efficacy. 22 patients with advanced cancers (gastric, n = 8; colorectal, n = 3; ovarian, n = 3; other, n = 8) received IM156 100 to 1,200 mg either QOD or QD. There were no DLTs. However, 1,200 mg QD was not well tolerated due to nausea; 800 mg QD was determined as the RP2D. The most frequent treatment-related AEs (TRAEs) were nausea (n = 15; 68%), diarrhea (n = 10; 46%), emesis (n = 9; 41%), fatigue (n = 4; 18%) and abdominal pain, constipation, and blood lactate increased (n = 2 each; 9%). Grade 3 nausea (n = 3; 14%) was the only grade ≥ 3 TRAE. Plasma exposures increased dose proportionally; mean Day 27 area under the curve (AUC0-24) values were higher following QD administration compared to the respective QOD regimen. Stable disease (SD), observed in 7 (32%) patients (confirmed in 2 [9%]), was the best response. To our knowledge, this is the first phase 1 study of an OXPHOS inhibitor that established a RP2D for further clinical development in cancer. Observed AEs of IM156 were manageable and SD was the best response.

Abnormal lipid metabolism may play an important role in the development of nontraumatic osteonecrosis of the femoral head (ON). By comparing lipid biomarkers in patients with ON and osteoarthritis (OA) after propensity score matching, we sought to reveal (1) common lipid biomarkers that are abnormal in ON regardless of the etiology and (2) specific lipid biomarkers associated with ON according to the etiology.Among 2,268 patients who underwent primary THA, 1,021 patients were eligible for this study. According to the Association Research Circulation Osseous criteria, ON was classified as either idiopathic (n = 230), alcohol-associated (n = 293), or glucocorticoid-associated ON (n = 132). Most common cause of OA was hip dysplasia in 106 patients (47%). We investigated patient lipid profiles by assessing total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), apolipoprotein (Apo) A1 and B, lipoprotein (a) levels and ApoB/A1 ratio. Since age and body mass index affect the lipid profile, we performed propensity score matching to select 304 patients for final analysis and compared lipid profiles between the ON and OA groups. We also compared biomarkers between the ON subgroups and the OA group.Overall, the ON group showed lower HDL-C (p0.001), higher TGs (p = 0.001) levels and higher ApoB/A1 ratio (p = 0.003). Idiopathic ON patients demonstrated lower HDL-C (p = 0.032), higher TGs (p = 0.016), ApoB (p = 0.024) levels and ApoB/A1 ratio (p = 0.008). The alcohol-associated ON subgroup showed lower HDL-C (p0.001), higher TGs (p = 0.010) levels and ApoB/A1 ratio (p = 0.030). Finally, the steroid-associated ON subgroup demonstrated lower HDL-C (p = 0.003), higher TGs (p = 0.039), lower TC (p = 0.022), LDL-C (p = 0.021), and ApoA1 (p = 0.004) levels.Higher TGs and lower HDL-C levels were associated with nontraumatic ON regardless of the etiology. Additionally, idiopathic ON was associated with higher ApoB levels and ApoB/A1 ratio. Alcohol-associated ON was related to higher ApoB/A1 ratio, and steroid-associated ON paired with decreased TC, LDL-C, and ApoA1 levels. Our findings may support future efforts for prevention and management of nontraumatic ON.Diagnostic Level III.

As an alternative to other approaches to facial rejuvenation, the air-toxin technique (dermal injection of air with micro-doses of botulinum toxin) is a promising method. We aimed to describe this novel technique and assess the overall safety and efficacy of the air-toxin technique in facial rejuvenation.A retrospective chart review was performed on cases treated with the air-toxin technique. A total of 47 Korean patients underwent a single treatment session. Treatment efficacy was assessed objectively with serial VISIAA significant improvement in wrinkle (p 0.001), UV spot (p 0.001), and porphyrin (p = 0.005) was objectively seen at 12 weeks follow-up. Patients noted improvement in the categories wrinkle (p 0.01), redness (p = 0.029), texture (p 0.001), dilated pore (p 0.001), and lifting (p 0.001) at Week 12 compared to baseline. No major adverse event was reported.Our data show that the air-toxin technique is efficacious in facial rejuvenation as shown by improved skin analysis parameters and patient assessment scores. Notably, there was some discrepancy between the objective and subjective parameters of improvement.

Although it is not recognized as essential to test for antiphospholipid antibody (aPL) in stroke of unknown cause, aPL-related stroke may account for a considerable number of cryptogenic strokes. We aimed to assess the current status and diagnostic value of aPL testing in cryptogenic stroke patients.Consecutive patients admitted with acute ischemic stroke were examined to confirm the factors associated with performing aPL testing and with positive aPL test results in real-world practice. Cryptogenic stroke patients were separately examined in the same manner. The antibody profiles of cryptogenic stroke patients with aPL positivity were compared by age.Among 2947 patients, 606 (20.6%) were tested for aPLs and 129 (21.3%) were positive. Physicians tended to perform aPL testing in patients aged50 years and in cryptogenic stroke patients. Cryptogenic stroke was a strong predictor of positive aPL results (adjusted odds ratio 3.70, 95% confidence interval 2.38-5.76). However, aPL positivity did not differ by age in stroke patients. Among 283 cryptogenic stroke patients, 136 (48.1%) were tested for aPLs and 56 (41.2%) were positive. aPL tests were performed predominantly in patients aged50 years rather than in older patients, even among cryptogenic stroke patients. The two age groups had similar positivity rates of40% (50 years: 43.2%; ≥50 years: 40.4%; p = 0.92) and their antibody profiles were similar.A significant number of patients with cryptogenic stroke had positive aPL results regardless of age. aPL testing may offer additional diagnostic opportunities in cryptogenic stroke patients, and thus may reduce the incidence of cryptogenic stroke.

Housing is an important social determinant of health. We investigated effects of changes in housing tenure and affordability on depressive symptoms.Data of 9,956 individuals aged20 years from the Korea Welfare Panel Study (2015-2020) were analyzed. Housing tenure was categorized as homeowners or tenants. Individuals with housing-related expenditures exceeding 30% of household income were defined as having housing unaffordability. Analyses using generalized estimating equations were conducted to evaluate the relationship between changes in housing tenure and affordability on depressive symptoms measured with the Center for Epidemiologic Studies Depression Scale.Individuals who became tenants (β = 0.326, p = 0.027) or were persistent tenants (β = 0.542, p0.001) demonstrated significantly more severe depressive symptoms than persistent homeowners. Individuals with new (β = 0.562, p0.001) or consistent housing unaffordability (β = 1.032, p = 0.036) showed increased depressive symptoms compared with those with persistent housing affordability. Depressive symptoms were reduced in new homeowners and those who left housing unaffordability status (β = -0.807, p = 0.031). The interaction between housing tenure and affordability on depressive symptoms differed by age and household composition. Housing tenure at post-retirement age and single-person households were associated with a decrease in depressive symptoms, respectively.All housing-related factors, especially different domains of housing insecurity including unstable neighborhoods or reasons for moving, have not been identified.Changes in housing tenure, affordability, and the two combined were significantly associated with depressive symptoms. Furthermore, the degree of interactive effect varied among age groups and household composition. Housing welfare policies that can stabilize housing tenure and affordability might help prevent depression.

Background/Aim: Bronchiectasis has long been neglected, unlike chronic obstructive pulmonary disease (COPD) and asthma. Recent clinical trials have shown that long-term use of azithromycin or erythromycin reduce exacerbations of non-cystic fibrosis (non-CF) bronchiectasis. Because of this, we should actively try to treat patients susceptible to severe status. Patients and Methods: We enrolled patients who had been diagnosed with bronchiectasis at five branches of the Catholic Medical Center between January 2015 to December 2017. We retrospectively analyzed these patients for demographic characteristics such as sex, age, body mass index (BMI), history of smoking and tuberculosis, bacterial colonization, pulmonary function, hospitalizations, and other exacerbations. Results: Colonization was shown to have a statistically significant association with hospitalization. A three-year follow up period showed that the mean frequency of hospitalization in patients without colonization was 0.8 times, compared to 0.7 times and 1.9 times, respectively in patients with NTM colonization and with other bacterial colonization (p-value=0.03). Patients with a lower BMI also had an increased risk of hospitalization (p-value=0.024). Current smokers had increased risk of mortality as compared to those who had never smoked (HR=11.29, p-value 0.015). Patients with a high BMI also had low risk of mortality as compared to patients with a low BMI (HR=0.76, p-value 0.005). Conclusion: Patients with bronchiectasis having chronic colonization, low BMI, or who are current smokers tend to be at greater risk for severe illness. Therefore, physicians should actively treat these patients to prevent exacerbations and mortality.

Objectives: The aim of this study was to identify the association between cohabitation status and sleep quality in family members of people with dementia (PwDs).Methods: Data of 190 365 participants aged ≥19 years from the 2018 Korea Community Health Survey were analyzed. Participants were categorized according to their cohabitation status with PwDs. Multiple logistic regression and ordinal logistic regression analyses were performed to evaluate the relationship between the cohabitation status of PwDs’ relatives and sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) and PSQI subscales.Results: Compared to participants without PwDs in their families, both cohabitation and non-cohabitation with PwDs were associated with poor sleep quality (cohabitation, male: odds ratio [OR],1.28; 95% confidence interval [CI], 1.08 to 1.52; female: OR, 1.40; 95% CI, 1.20 to 1.64; non-cohabitation, male: OR, 1.14; 95% CI, 1.05 to 1.24; female: OR, 1.23; 95% CI, 1.14 to 1.33). In a subgroup analysis, non-cohabiting family members showed the highest odds of experiencing poor sleep quality when the PwD lived alone (male: OR, 1.48; 95% CI, 1.14 to 1.91; female: OR, 1.58; 95% CI, 1.24 to 2.01). Cohabiting male and female participants had higher odds of poor subjective sleep quality and use of sleeping medications than non-cohabiting male and female participants, respectively.Conclusions: The residence of PwDs and cohabitation status may contribute to poor sleep quality among PwDs’ family members. The circumstances faced by cohabiting and non-cohabiting family members should be considered when evaluating sleep quality in family members of PwDs, and appropriate interventions may be needed to improve sleep quality in both cohabiting and non-cohabiting family members.

Context Despite previous studies regarding the association between smoking and diabetes, the effects of electronic cigarettes and secondhand smoke (SHS) on glucose metabolism and insulin sensitivity have not been fully elucidated. Objective To examine the association of mixed electronic and conventional cigarette use and exposure to SHS with prediabetes. Design Data from the 2014-2018 Korean National Health and Nutrition Examination Survey were analyzed. Setting Nationwide population-based. Participants Of 39 199 participants, 22 385 participants (9490 men, 12 895 women) without diabetes were included. The main independent variables were smoking behaviors, including exposure to SHS. Interventions None. Main Outcome Measures Prediabetes (hemoglobin A1C of 5.7-6.4%). Results Of 22 385 participants without diabetes, 6735 had prediabetes. Mixed cigarette use was associated with a 1.57-fold increase in the odds of prediabetes when compared with never-smoking [odds ratio (OR) = 1.57, 95% CI = 1.29-1.92] and a 1.27-fold increase when compared with conventional cigarette use only (OR = 1.27, 95% CI = 1.07-1.52). Participants who were current nonsmokers, but mixed users in the past had an increased risk of prediabetes (OR = 1.54, 95% CI = 1.04-2.13). There was no significant association between prediabetes and current nonsmoking in individuals with previous conventional cigarette use only. Among never-smokers, exposure to SHS significantly increased the risk of prediabetes (OR = 1.16, 95% CI = 1.04-1.30). Conclusions Mixed use of electronic and conventional cigarettes and exposure to SHS increased the risk of prediabetes. Further studies are required to comprehensively investigate the molecular biology underlying the effects of previous and current mixed use of electronic cigarettes and SHS on glucose metabolism.

Background Many researchers have questioned whether shoulder kinematics such as the glenohumeral position and scapular kinematics would be different in different age groups. However, studies comparing shoulder kinematics between different age groups have been rare. The aim of this study was to analyze and compare the three-dimensional (3D) glenohumeral position, scapular kinematics, and scapulohumeral rhythm (SHR) during scapular plane arm abduction between a normal young male group and a normal older male group. Methods Twenty normal men (10 young and 10 older) were enrolled in this controlled laboratory study. Fluoroscopic images were obtained using a single plane X-ray system. Bilateral computed tomography scans were taken to create a 3D model. A 3D-2D registration technique was used to determine the 3D position and orientation of the bones of the shoulder. Results During scapular plane arm abduction, there were significant differences in scapular kinematics between the groups. The older male group showed more upward rotation, posterior tilt, and external rotation than the young male group. On the other hand, the glenohumeral position such as superior inferior translation, anterior posterior translation, and external rotation of the humeral head did not show significant difference between the groups. The mean value of SHR for the overall arm elevation range from start to maximum elevation angle for the older group and young group was 2.298 ± 0.964 and 2.622 ± 0.931, respectively, showing a significant difference between the two groups (p = 0.035). Conclusions Scapular kinematics and SHR were significantly different between the older male group and the young male group. Our study could provide reference values of shoulder kinematics for older men aged 55-65 years.

Methicillin-resistant

Inadvertent intravascular injection of local anesthetics can lead to false-negative results following lumbar medial branch block (MBB) performed to diagnose facet joint origin pain. A previous study demonstrated that the type of approach method could affect the incidence of intravascular injections and technical ease of the procedure.The primary objective of our study was to compare the incidence of inadvertent intravascular injection and technical ease of the MBB between anteroposterior (AP) and oblique (OB) views.Prospective randomized trial.An interventional pain management practice in South Korea.The incidence of intravascular uptake of contrast medium was compared using AP and OB fluoroscopic views during lumbar MBB. Injection time, radiation dose, and patient discomfort during lumbar MBB were also compared. Risk factors associated with a longer procedure time and a higher radiation dose were analyzed.The incidence of intravascular injection was 22.5% (23/102) in the AP group and 17.6% (18/102) in the OB group (P = 0.382). A significantly longer injection time and a higher dose of radiation were required to complete 3 levels of MBB in the OB group than in the AP group (45.9 seconds vs 61.9 seconds, P = 0.001; 27.4 centigray [cGy]/cm2 vs 42.2 cGy/cm2, I = 0.004). The OB approach and left side injection were the risk factors associated with a longer total procedure time (odds ratio [OR] = 6.64, 95% CI, 1.99-22.17, P = 0.002; OR = 0.20, 95% CI, 0.06-0.67, P = 0.009, OB and AP, respectively).The physician performing the MBB could recognize the AP or OB fluoroscopic view during procedure.The overall incidence rate of intravascular injection during lumbar MBB showed nearly 20% in both approach methods groups. The OB approach and left side MBBs were associated with a longer total procedure time and a higher radiation dose.

Forkhead Box M1 (FOXM1) is known to regulate cell proliferation, apoptosis and tumorigenesis. The lignan, (−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. The present study hypothesized that DFS can have anti-cancer effects against glioblastoma (GBM) tumorspheres (TSs). Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of β-catenin through β-catenin/FOXM1 binding. DFS-pretreated GBM TSs were evaluated to assess the ability of DFS to inhibit GBM TSs and their transcriptional profiles. The in vivo efficacy was examined in orthotopic xenograft models of GBM. Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked β-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS inhibited cell viability and ATP levels, while increasing apoptosis, and it reduced tumorsphere formation and the invasiveness of GBM TSs. And DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. It suggests that DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. DFS may be a potential therapeutic agent to treat GBM.

Synthetic biomaterials are used to overcome the limited quantity of human-derived biomaterials and to impart additional biofunctionality. Although numerous synthetic processes have been developed using various phases and methods, currently commonly used processes have some issues, such as a long process time and difficulties with extensive size control and high-concentration metal ion substitution to achieve additional functionality. Herein, we introduce a rapid synthesis method using a laser-induced hydrothermal process. Based on the thermal interaction between the laser pulses and titanium, which was used as a thermal reservoir, hydroxyapatite particles ranging from nanometer to micrometer scale could be synthesized in seconds. Further, this method enabled selective metal ion substitution into the apatite matrix with a controllable concentration. We calculated the maximum temperature achieved by laser irradiation at the surface of the thermal reservoir based on the validation of three simplification assumptions. Subsequent linear regression analysis showed that laser-induced hydrothermal synthesis follows an Arrhenius chemical reaction. Hydroxyapatite and Mg

Depression in older adults is a global socioeconomic burden. Identifying factors, such as physical activity or exercise that can help prevent depression is important. We aimed to investigate the relationship between changes in handgrip strength and the presence of depression using longitudinal, nationwide data of older Korean adults. Data from the Korean Longitudinal Study of Aging were used in this study. A total of 6783 participants who had undergone a handgrip strength test and completed the short-form Center for Epidemiologic Studies Depression Scale (CESD-10-D) questionnaire from 2006 to 2018 were included. General estimating equations were used to assess the temporal effect of the changes in handgrip strength on depression. A decrease in handgrip strength was associated with high CESD-10-D scores (β = 0.1889 in men, β = 0.1552 in women). As a continuous variable, handgrip strength was negatively correlated with CESD-10-D scores(β = − 0.0166 in men, β = − 0.0196 in women). Changes in the handgrip strength were associated with depressive symptoms in our longitudinal study. Those who experienced a decrease in handgrip strength had severe depressive symptoms compared to those with unchanged or increased handgrip strength. These findings can be used to guide general health policies for the prevention of depression.

Although previous studies have demonstrated increased depression related to COVID-19, the reasons for this are not well-understood. We investigated the association of compliance with COVID-19 public health measures with depression. Data from the 2020 Korea Community Health Survey were analyzed. The main independent variable was compliance with rules based on three performance variables (social distancing, wearing a mask in indoor facilities, and outdoors). Depression was assessed using Patient Health Questionnaire-9 scores. Of 195,243 participants, 5,101 participants had depression. Bad and moderate performance scores for compliance were associated with depression (Bad score, men: adjusted odds ratio [aOR] = 2.24, 95% confidence interval [CI] = 1.29–3.87; women: aOR = 2.42, 95% CI = 1.42–4.13; moderate score, men: aOR = 1.31, 95% CI = 1.02–1.68; women: aOR = 1.28, 95% CI = 1.07–1.53). In the subgroup analysis, among the quarantine rules, not wearing a mask indoors was the most prominently associated with depression. In participants with a high level of education, non-compliance with quarantine rules was significantly associated with depression. People who do not comply with public health measures are more likely to be depressed. The preparation and observance of scientific quarantine rules can help mental health in the ongoing COVID-19 pandemic and another infectious disease pandemic that may come.

Progress in neurological research has experienced bottlenecks owing to the limited availability of purified primary neurons. Since neuronal cells are non-proliferative, it is necessary to obtain purified neurons from animal models or human patients for experimental work. However, currently available methods for purifying primary neurons are time-consuming (taking approximately 1 week), and suffer from insufficient viability and purity. Here, we report a method for rapid enrichment of neurons from the mouse embryonic dorsal root ganglion (DRG), using a fully-automated continuous centrifugal microfluidics (CCM) based neuron purification disc (NPD). Non-neuronal cells were removed

The South Korean government is seeking information on the environmental conservation value (ECV) of Cypripedium japonicum, a plant on the first-level priority endangered species list of the Korea Ministry of Environment, as well as on the Red List of the International Union for Conservation of Nature. This research paper aims to assess the ECV by employing contingent valuation (CV) to elicit people's willingness to pay (WTP) for its conservation. To achieve this aim, in May 2020, a CV survey of 1,000 interviewees in South Korea was carried out employing a closed-ended question. The average household WTP is estimated to be KRW 3,770 (USD 3.07) per annum and secures statistical significance. From a national point of view, using information on the national population, this value comes to KRW 76.72 billion (USD 62.42 million) per year. Although the cost of conserving the species has not yet been accurately estimated, the ECV seems to be larger than the cost of conservation. Thus, it is socially desirable to conserve Cypripedium japonicum, and the conservation should be carried out in a stable and continuous manner.

Specific features of the human body, such as fingerprint, iris, and face, are extensively used in biometric authentication. Conversely, the internal structure and material features of the body have not been explored extensively in biometrics. Bioacoustics technology is suitable for extracting information about the internal structure and biological and material characteristics of the human body. Herein, we report a biometric authentication method that enables multichannel bioacoustic signal acquisition with a systematic approach to study the effects of selectively distilled frequency features, increasing the number of sensing channels with respect to multiple fingers. The accuracy of identity recognition according to the number of sensing channels and the number of selectively chosen frequency features was evaluated using exhaustive combination searches and forward-feature selection. The technique was applied to test the accuracy of machine learning classification using 5,232 datasets from 54 subjects. By optimizing the scanning frequency and sensing channels, our method achieved an accuracy of 99.62%, which is comparable to existing biometric methods. Overall, the proposed biometric method not only provides an unbreakable, inviolable biometric but also can be applied anywhere in the body and can substantially broaden the use of biometrics by enabling continuous identity recognition on various body parts for biometric identity authentication.

Recognizing the lesion pattern of antiphospholipid antibody-related stroke (aPL-stroke) may contribute to establishing the cause in patients with cryptogenic stroke. We aimed to describe the neuroimaging features of aPL-stroke compared with atrial fibrillation-related stroke (AF-stroke), a major hidden cause of cryptogenic stroke. Using a prospective stroke registry, we identified consecutive aPL- and AF-stroke patients without other potential causes of stroke. Neuroimaging features based on diffusion-weighted imaging and angiographic findings at admission were compared. A total of 56 and 333 patients were included in the aPL- and AF-stroke groups, respectively. aPL-stroke patients more often presented with single small lesions (aPL-stroke, 30.4% vs. AF-stroke, 7.5%, p p p p p = 0.44). In comparison only including patients with multi-territory lesions as well, aPL-stroke patients showed small lesion dominance and smaller infarct volume. Multivariate analyses showed independent associations between mild neuroimaging features (small lesion prevalence, smaller infarct volume, and absence of relevant artery occlusion) and aPL-stroke. Patterns of small lesion prevalence, small infarct volume, and absence of relevant artery occlusion were suggestive of aPL-stroke rather than AF-stroke. Cryptogenic stroke patients with such neuroimaging features may benefit from aPL testing for a precise diagnosis.

Etomidate, with efficacy similar to that of propofol, has been used as a propofol substitute because propofol is a designated narcotic drug, and an increase in the frequency of illegal distribution and misuse has been reported in Korea. Previous analytical studies on etomidate used blood and urine. For long-term use and timing estimation, a method for etomidate analysis using hair should be developed. Therefore, in this study, an analytical method using LC-MS/MS was developed to determine etomidate and its major metabolite in hair. Human hair samples were segmented after washing to eliminate possible contaminants on the hair and stirred with methanol. The LC-MS/MS conditions were optimized, and the chromatographic separation time was 10 min. Selectivity, linearity, limit of detection, limit of quantification, precision, accuracy, recovery, process efficiency, matrix effect, and stability were evaluated to validate the analytical method. The calibration curves ranged from 0.25 to 50 pg/mg for etomidate and 2-250 pg/mg for etomidate acid; the coefficients of determination were higher than 0.997. The intra- and inter-assay precision results for all the compounds were15% and satisfied at recovery, process efficiency, matrix effect, and stability. In addition, this method was applied to the hair of 4 rats which are administered with etomidate to evaluate. The etomidate concentrations in the rat hair ranged from 2.60 to 8.50 pg/mg, and the etomidate acid concentrations were 2.06-7.13 pg/mg. Thus, this method can be used as basic data for monitoring etomidate in hair.

Background Studies investigating the association between migraine and dementia have reported inconsistent findings. This study aimed to evaluate whether patients with migraine have an increased risk of dementia compared to individuals without migraine. Methods We obtained data from the 2002–2019 Korean National Health Insurance Health Screening Cohort. Non-migraine controls were selected using a 1:1 risk-set matching with a time-dependent propensity score. The main outcome was the development of all-cause dementia, and the secondary outcome was the development of each cause of dementia (Alzheimer’s, vascular, mixed or other specified, and unspecified dementia). The incidence rate of dementia was calculated using Poisson regression, and the association between migraine and dementia was evaluated using Cox proportional hazards regression. Results Among 88,390 participants, 66.1% were female, and the mean baseline age was 55.3 ± 9.4 years. During the study period, dementia cases were identified in 4,800 of the 44,195 patients with migraine and 3,757 of the 44,915 matched controls. The incidence rate of dementia was 139.6 (95% confidence interval [CI], 135.7–143.5) and 107.7 (95% CI, 104.3–111.1) cases per 10,000 person-years in patients with migraine and matched controls, respectively. Patients with migraine had a 1.30 (hazard ratio [HR], 1.30; 95% CI, 1.25–1.35), 1.29 (HR, 1.29; 95% CI, 1.23–1.35), 1.35 (HR, 1.35; 95% CI, 1.19–1.54), 1.36 (HR, 1.36; 95% CI, 1.00–1.83), and 1.30 (HR, 1.30; 95% CI, 1.17–1.45) times higher risk of developing all-cause dementia, Alzheimer’s dementia, vascular dementia, mixed or other specified dementias, and unspecified dementia than their matched controls, respectively. Conclusion Our results suggest that migraine is associated with an increased risk of subsequent dementia. Further research is warranted to confirm these findings and to reveal the underlying mechanisms.

There is a clear relationship between rheumatoid arthritis (RA) and major osteoporotic fracture (MOF), although there is limited evidence on the effect of continuity of care (COC) on MOF in these patients. We investigated the association between COC and risk of MOF, including fractures of the lumbar spine and pelvis, forearm, and hip, among newly diagnosed RA patients aged ≥ 60 years. A total of 8715 incident RA patients from 2004 to 2010 were included from the Korean National Health Insurance Service-Senior cohort database. Participants were categorized into a good and bad COC group according to the COC index. The cumulative incidence of MOF was higher in RA patients with bad than in those with good COC (p

Background Parkinson’s disease (PD) is an increasingly common neurodegenerative disease in an aging society. Whether PD is associated with an increased suicide risk is unclear. Thus, we investigated the effect of new-onset PD on suicide. Methods Using the National Health Insurance Service Senior Sample Cohort of South Korea, 17,143 incident PD patients and 17,143 risk set controls, matched by propensity score, were selected for follow-up. The incidence rate of suicide and 95% confidence interval (CI) were calculated based on a generalized linear model of the Poisson distribution. Effect sizes were expressed as hazard ratios (HRs) using the Cox proportional hazards model with a robust variance estimator that incorporated clustering within matched pairs. Results The incidence rate of suicide was 206.7 cases per 100,000 person-years (95% CI, 172.8–246.9) among the PD cohort. Compared to the matched controls, patients with PD were 2.64 times (HR, 2.64; 95% CI, 1.31–5.30) more likely to commit suicide during the first 180 days of follow-up and 2.47 times (HR, 2.47; 95% CI, 1.42–4.28) within the first 365 days of follow-up. During the entire follow-up period, patients with PD were 2.26 times more likely to commit suicide than were their matched controls (HR, 2.26; 95% CI, 1.67–3.06). Conclusion Our findings indicated an increased risk of suicide in patients with new-onset PD, regardless of the period after diagnosis. Incorporating mental health care with social and environmental interventions into primary care and PD-specialized care can help reduce suicide risk in people with PD, improving suicide prevention, identification, and risk assessment.

SummaryTAS-117 is a potent and selective allosteric pan-v-akt murine thymoma viral oncogene homolog (Akt) inhibitor. We conducted a single-arm single-center phase 2 study of TAS-117 in heavily treated patients with tumors refractory to systemic chemotherapy and harboring phosphatidylinositol 3-kinase (PI3K)/Akt mutations. Patients with gastrointestinal (GI) cancers were orally administered 16 mg TAS-117 daily, and those with non-GI tumors were administered 24 mg on a 4 days on/3 days off schedule. The primary endpoint was overall response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), PFS ratio, safety, and tolerability. Thirteen patients were enrolled: eight with non-GI (breast, ovarian, endometrial, and non-small cell lung) and five with GI (colon, rectal, gastric, and gallbladder) cancers. Ten patients were treated with TAS-117 after ≥ 4 lines of therapy. Twelve patients showed PIK3 catalytic subunit alpha (PIK3CA) mutations; one harbored an Akt1E17K mutation. The median treatment duration was 1.4 months; the median number of treatment cycles was 2. The ORR was 8 %, and DCR was 23 %. The median PFS and OS were 1.4 and 4.8 months, respectively. Grade 3–4 treatment-related adverse events were anorexia (grade 3, 8 %) and hyperglycemia (grade 3, 8 %; grade 4, 8 %).Grade 3–4 treatment-related adverse events occurred in 27 % of grade 3 anorexia (9 %) and hyperglycemia (grade 3, 8 %; grade 4, 9\%). TAS-117 showed limited antitumor activity and manageable toxicity. Clinical efficacy was observed in patients with ovarian cancer harboring PIK3CA E545K mutations and in patients with breast cancer harboring PIK3CA H1047R and Akt1E17K mutations.Trial registration: This study was retrospectively registered with ClinicalTrial.gov (NCT03017521 on January 11, 2017).

As the clinical failure of glioblastoma treatment is attributed by multiple components, including myelin-associated infiltration, assessment of the molecular mechanisms underlying such process and identification of the infiltrating cells have been the primary objectives in glioblastoma research. Here, we adopted radiogenomic analysis to screen for functionally relevant genes that orchestrate the process of glioma cell infiltration through myelin and promote glioblastoma aggressiveness. The receptor of the Nogo ligand (NgR1) was selected as the top candidate through Differentially Expressed Genes (DEG) and Gene Ontology (GO) enrichment analysis. Gain and loss of function studies on NgR1 elucidated its underlying molecular importance in suppressing myelin-associated infiltration in vitro and in vivo. The migratory ability of glioblastoma cells on myelin is reversibly modulated by NgR1 during differentiation and dedifferentiation process through deubiquitinating activity of USP1, which inhibits the degradation of ID1 to downregulate NgR1 expression. Furthermore, pimozide, a well-known antipsychotic drug, upregulates NgR1 by post-translational targeting of USP1, which sensitizes glioma stem cells to myelin inhibition and suppresses myelin-associated infiltration in vivo. In primary human glioblastoma, downregulation of NgR1 expression is associated with highly infiltrative characteristics and poor survival. Together, our findings reveal that loss of NgR1 drives myelin-associated infiltration of glioblastoma and suggest that novel therapeutic strategies aimed at reactivating expression of NgR1 will improve the clinical outcome of glioblastoma patients.

Background and Purpose: Although it has been reported that the amount of alcohol consumption has a J-shaped association with ischemic stroke, it is unclear whether differences in drinking patterns affect this relationship. We aimed to clarify the impact of drinking patterns on ischemic stroke in midlife. Methods: We used data from the National Health Insurance Service-National Sample Cohort, which is a large-sized, standardized population cohort in Korea. Five different drinking patterns were defined by combining the frequency of alcohol consumption and quantity of alcohol consumed per occasion, that is, abstainers, not drinking alcohol; drinker group I, ≤30 g/d and 30 g/d and 30 g/d and ≥5 d/wk. The association between the drinking patterns and ischemic stroke occurrence was analyzed using the Cox proportional hazard model. Results: A total of 152 469 middle-aged participants (mean age, 50.2 years; 72 285 men [47.4%]) were eligible for the analyses. The median follow-up time was 9.0 years. Compared with abstainers, those who drank Conclusions: Reduced risk of ischemic stroke was observed in middle-aged participants with specific drinking patterns, but it was limited to the earlier period. Physicians should be cautious in educating patients on alcohol consumption, considering the long-term association between drinking patterns and ischemic stroke.

Background: The purpose of this study was to investigate the effect of general anesthesia on microvascular reactivity and tissue oxygen saturation (StO2) using near-infrared spectroscopy in conjunction with vascular occlusion tests (VOT). Age-related changes of microvascular reactivity, that is, the capacity of capillary recruitment, were examined. Methods: This prospective observational study was performed on 60 patients without comorbidities who underwent elective surgery under general anesthesia. Baseline StO2 on thenar eminence, hemodynamics, and laboratory profile were monitored before (T0) and 30 min after general anesthesia (T1). During VOT, occlusion slope representing oxygen consumption of muscle and recovery slope representing microvascular reactivity were also collected at T0 and T1. Results: Baseline StO2 and minimum / maximum StO2 during VOT increased under general anesthesia. Occlusion slope decreased while the recovery slope increased under general anesthesia. To observe aging effect, Receiver operating characteristic analysis was performed and age less than 65 years old showed a fair performance in predicting the increase of microvascular reactivity after the induction of anesthesia (AUC 0.733, 95% CI 0.594-0.845, P= 0.003). For age-related analyses, 27 patients of younger group (< 65 years) and 26 patients of older group (≥ 65 years) were divided. Recovery slope significantly increased under general anesthesia in younger group (2.44 [1.91-2.81] % ∙ sec-1 at T0 and 3.59 [2.58-3.51] % ∙ sec-1 at T1, P

Aurelia aurita (AA), a legally registered harmful marine organism in South Korea, is damaging marine human leisure activities, local residents' tourism income, fisheries, and cooling water intake at power plants. The government is therefore seeking to eradicate AA by removing AA-attached larvae (polyps). This article looks into the public willingness to pay (WTP) for the eradication, utilizing a contingent valuation. For the sake of eliciting the WTP response, the one-and-one-half-bounded (OB) model was adopted. For comparison, the single-bounded (SB) model, which uses only the response to the first question in the OB model, was also applied. A spike model with a considerable plausibility that could explicitly deal with zero WTP responses was employed. Consequently, the estimation results of the SB model were used for further policy analysis. The household average WTP was estimated as KRW 3,911 (USD 3.49) per year, securing statistical significance. The national value was KRW 80.46 billion (USD 71.71 million) per annum. This figure can be interpreted as public value of the AA eradication project and used as essential basic data to evaluate the economic feasibility of implementing the project. Some factors such as income and education level significantly positively affected the intention of paying a suggested bid.

Understanding cancer heterogeneity is essential to finding diverse genetic mutations in metastatic cancers. Thus, it is critical to isolate all types of CTCs to identify accurate cancer information from patients. Moreover, full automation robustly capturing the full spectrum of CTCs is an urgent need for CTC diagnosis to be routine clinical practice.

The purpose of this study is to suggest priority tasks necessary for building a sustainable healthcare system in Korea based on the Delphi consensus among healthcare professionals.Twenty-five items covering the three categories that make up healthcare policy (healthcare demand, supply, and environment) were selected based on a literature evaluation. Email surveys were also analyzed using a two-round modified Delphi method. Of 59 experts, 21 completed the first and second rounds. Each item asked about the degree of importance and urgency, and the answers were rated on a 9-point Likert scale. A coefficient of variation less than 50% for each item in the Delphi survey meant that consensus was reached. Only items that meet a predetermined threshold are prioritized (agreement ≥ 90%, average importance score and urgency score ≥ 6.5).Eight items that satisfy all three criteria were set as priorities for a sustainable healthcare system. These tasks are "Securing the financial soundness of the National Health Insurance (NHI)," "Solving the problem of low fertility," "Strengthening response to public health crises such as infectious or environmental diseases," "Bio-health technology innovation using D.N.A (Data, Network, AI)," "Intensive management of dementia patients," "Mental healthcare and suicide prevention," "Reform of the operation structure of the NHI Service," and "Reform the healthcare delivery system and payment system."The eight items for which consensus was reached in this study should be prioritized for Korea's sustainable healthcare system. Health policy makers will need to put considerable effort into researching and establishing these priorities.

STUDY OBJECTIVES: Although the airway mucosal system plays a pivotal role in the pathogenesis of obstructive sleep apnea (OSA), the underlying disease mechanism remains unclear. The microbiome greatly impacts human health and disease, particularly in the mucosa, where it can have direct interactions. In this study, we aimed to analyze the microbiome composition in the upper airway mucosa of individuals with and without OSA to identify potential disease severity–related microbial signatures. METHODS: This population-based cohort study involved 92 participants (mean age = 62.7 ± 5.8 years; male-to-female ratio = 0.74) who underwent a physical examination and sleep study. Upper airway swab samples were collected from the nasopharyngeal mucosa to evaluate the microbiome based on 16S rRNA gene pyrosequencing. The relationship between microbiome composition and sleep parameters was explored through bioinformatics analysis. RESULTS: The average apnea-hypopnea index was 7.75 ± 6.5 events/h. Proteobacteria, Firmicutes, and Actinobacteria were the predominant phyla in the nasopharyngeal microbiota in all participants. Simpson diversity indexes were higher in patients with OSA (0.6435 ± 0.2827) than in the control patients (0.6095 ± 0.2683); however, the difference was not significant (P = .1155). Specific anaerobes negatively correlated with the lowest oxygen saturation level during sleep (sum of powered score (1) = –117.47; P = .0052). CONCLUSIONS: The upper airway microbiome of older patients with mild-moderate OSA exhibited minor differences in composition compared with that of individuals without OSA, possibly owing to environmental changes in the upper airway mucosa resulting from recurrent airway obstruction and intermittent hypoxia in patients with OSA. CITATION: Hong S-N, Kim KJ, Baek M-G, et al. Association of obstructive sleep apnea severity with the composition of the upper airway microbiome. J Clin Sleep Med. 2022;18(2):505–515.

South Korea is pursuing an energy transition policy (ETP) of expanding the use of renewable energy and natural gas and decreasing that of nuclear energy and coal in total generation. An investigation of whether the public is for or against the ETP is needed by the government. This article explores the public preference toward the ETP employing the data collected through a survey of 1000 individuals. They were asked to reveal their preference for the ETP on a five-point scale in the survey. Overall, there are more advocates of the ETP than those who opposed it. For the purpose of analyzing the determinants of advocacy and opposition of the ETP, an ordered probit model is employed. The results suggest that people living in the Seoul Metropolitan area think that the environment is more important than new jobs, or know the renewable energy 100% campaign before the survey is more favorable to the ETP than others. However, people who use electricity for heating tend to be negative about the ETP. As the age increases, people approve of the ETP, but when age goes beyond a certain level, they oppose it.

Triple-negative breast cancer (TNBC) that lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) is a breast cancer subtype with very aggressive metastasis and poor prognosis. Unique cartilage matrix-associated protein (UCMA) is a vitamin K-dependent protein (VKDP) with a high-density γ-carboxyglutamic acid (Gla) domain due to the action of vitamin K. UCMA promotes osteoblast differentiation and mineral deposition in bone and suppresses calcification in vessels. However, correlation between UCMA and TNBC is unknown. This study investigated the inhibitory effect of UCMA on TNBC cell in vitro migration, invasion, and colony formation in addition to in vivo tumorigenesis. Cell migration and invasion significantly decreased in Ucma-overexpressing MDA-MB-231 and 4T1 cells compared to the mock control cells. Also, colony formation and the number of colonies significantly decreased in Ucma-overexpressing MDA-MB-231 and 4T1 cells. These results indicate that UCMA significantly inhibits the migration, invasion, and colony formation of TNBC cells. In an in vivo xenograft mouse model, tumor growth significantly decreased in mice bearing Ucma-overexpressing TNBC cells compared to the mock control cells, indicating that UCMA reduced in vivo tumor growth, similar to the inhibitory role of UCMA in vitro. Survival analysis using publicly available database showed that high UCMA expression significantly correlated with favorable relapse-free survival in TNBC patients compared to those with the other VKDPs, matrix Gla protein (MGP) and osteocalcin (OCN). Collectively, this study suggests that UCMA is a promising new therapeutic agent for TNBC.

Clinical Relevance When a resin nanoceramic inlay is cemented using self-adhesive cement, a universal dentin adhesive can be applied to the prepared cavity. The application of the adhesive before self-adhesive cement placement provides similar or better interfacial adaptation than without the adhesive. SUMMARY Purpose: The first objective of this study was to determine whether the luting material used for computer-aided design and computer-aided manufacture resin nanoceramic inlays affected interfacial adaptation. The second objective was to investigate whether application of a universal dentin adhesive before cementation affected interfacial adaptation. The final objective was to compare the inlay-side and dentin-side interfaces in the cement space. Methods and Materials: Seventy-four class I cavities were prepared on extracted human third molars. Cavities were optically scanned, and resin nanoceramic inlays were milled using Lava Ultimate blocks (3M ESPE). For the control groups, the fabricated inlays were cemented using Panavia V5 (Kuraray Noritake) or FujiCem 2 (GC). For the experimental groups, the teeth were randomly divided into groups I and II. Group I contained four subgroups using different luting materials; in all subgroups, the inlays were cemented and dual cured without pretreatment. Group II contained six subgroups in which inlays were cemented and dual cured after application of a universal dentin adhesive. After thermocycling, interfacial adaptation was measured using swept-source optical coherence tomography (SS-OCT) imaging and statistically compared among groups. Results: Interfacial adaptation was different depending on the luting material used (p0.05). Conclusions: Interfacial adaptation for resin nanoceramic inlays differed with luting material. For some self-adhesive cements, application of a universal adhesive before cementation improved interfacial adaptation.

Background The purpose of the study is to evaluate the in-hospital mortality of patients who presented with acute subdural hematoma (SDH) and underwent emergency decompressive craniectomy (DC) or craniotomy (CO) within 4 hours of hospital arrival. Method The National Trauma Data Bank (NTDB) dataset of the calendar year of 2007 through 2010 was accessed for the study. All blunt severe head injury patients who presented with acute SDH were included in the study. Severe head injury is defined as a head Abbreviated Injury Scale (AIS) score ≥3 and a Glasgow Coma Scale (GCS) score ≤8. Univariate followed by propensity-matched analyses were performed to compare the two procedure groups: DC and CO. Results Out of 2370 patients, 518, (21.9%) patients underwent DC. There were significant differences found in the univariate analysis between the DC and CO groups for median age (38 (IQR: 22.0, 55.0) vs 49 (IQR: 27, 67), P < .001), mechanism of injury (fall: 33.2% vs 50.7%; motor vehicle crashes: 58.3% vs 40.9%, P < .001), and median injury severity score (ISS: 26.0 (IQR: 25, 38) vs 26 (IQR: 25.0, 33.0), P < .001). After propensity score matching and pair-matched analysis, no differences were found with any of the above characteristics. The pair-matched analysis also showed no significant difference in in-hospital mortality (42.7% vs 37.5%, P = .10) between the DC vs CO groups. Conclusion The overall in-hospital mortality for emergency CO or DC for the evacuation of SDH remains high. The preference of one operative procedure over the other did not impact overall mortality.

Introduction Whether patients with resectable colorectal liver metastases (CRLM) gain a survival benefit from perioperative chemotherapy remains controversial. The benefit of including bevacizumab in chemotherapy also remains unclear. Material and Methods Seventy-six patients with CRLM were randomly assigned to either 6 cycles of FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin)/FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan) with bevacizumab before and after surgery or 12 cycles after surgery. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared by the log-rank test. Results The median PFS of all patients was 37.4 months at 5.4 years follow-up, and the median overall survival (OS) was not reached. The PFS between the perioperative group and the postoperative group did not reveal a statistical difference (P = .280). The OS was significantly better in the perioperative group (hazard ratio [HR], 0.60; 95% confidence interval [CI],) 0.35-1.02; P = .049). In subgroup patients with carcinoembryonic antigens (CEA) ≥ 5 ng/mL or those with over 2 liver metastases, perioperative group had longer OS than postoperative group (CEA: HR, 0.49; 95% CI, 0.25-0.93; P = .030; number of liver metastases: HR, 0.55; 95% CI, 0.30-0.99; P = .049). The largest liver metastases size, disease-free interval, and sidedness did not affect PFS or OS. There was no difference between the 2 groups in postoperative complications with bevacizumab or adverse events during chemotherapy. Conclusions In patients with resectable CRLMs, perioperative chemotherapy had no effect on PFS, but improved OS. Patients with high CEA levels or over 2 liver metastases may benefit from perioperative chemotherapy.

The liver is a highly regenerative organ, but its regenerative capacity is compromised in severe liver diseases. Hepatocyte-driven liver regeneration that involves the proliferation of preexisting hepatocytes is a primary regeneration mode. On the other hand, liver progenitor cell (LPC)-driven liver regeneration that involves dedifferentiation of biliary epithelial cells or hepatocytes into LPCs, LPC proliferation, and subsequent differentiation of LPCs into hepatocytes is a secondary mode. This secondary mode plays a significant role in liver regeneration when the primary mode does not effectively work, as observed in severe liver injury settings. Thus, promoting LPC-driven liver regeneration may be clinically beneficial to patients with severe liver diseases. In this review, we describe the current understanding of LPC-driven liver regeneration by exploring current knowledge on the activation, origin, and roles of LPCs during regeneration. We also describe animal models used to study LPC-driven liver regeneration, given their potential to further deepen our understanding of the regeneration process. This understanding will eventually contribute to developing strategies to promote LPC-driven liver regeneration in patients with severe liver diseases., Regenerative medicine: Understanding regeneration in liver disease A deeper understanding of the biology of liver progenitor cells (LPCs) could give clinicians more effective tools for reversing the effects of liver disease. LPCs are precursors of the liver cells known as hepatocytes, and naturally appear when the tissue is injured or diseased. Juhoon So, Donghun Shin and colleagues at the University of Pittsburgh, USA, have reviewed the current state of knowledge of LPC biology. They explore the mechanisms by which LPCs are generated and activated in response to trauma. These molecular pathways could offer useful drug targets.The authors also point out that excessive LPC activity can promote liver damage and tumorigenesis. As a consequence, any regenerative medicine approach based on LPCs must be coupled with effective strategies for promoting the efficient maturation of these cells into healthy hepatocytes.

Background and objectives Patients around the world use a lancing device to perform self-monitoring of blood sugar (SMBG). However, there are always fears of needles and pain. Therefore, less painful devices are being developed. The purpose of this study was to compare the usefulness and safety of a laser lancing device (without a needle) to a conventional needle lancet (with a needle) for capillary blood sampling. Study design/materials and methods A total of 40 healthy subjects were enrolled in the study. Capillary blood was collected from a laser lancing device (without a needle) and a conventional needle lancet (with a needle) on opposite fingers, the choice of which was randomly selected. The laser lancing device (LMT-3000) uses a 2940 nm mono-pulse laser, a radiation field of 350 μm, laser energy of 210 mJ, and a 3.7 V battery. One week later, capillary blood was obtained by switching the devices and fingers. The biochemical measurements and pain were compared between the two groups. Puncture pain was measured on a pain scale from 0 to 10. Result All patients were tested with both a laser lancing device and a conventional needle lancet. In the biochemical analysis, the blood glucose level was 103.21 ± 17.20 mg/dl in laser lancing device group and 102.25 ± 22.44 mg/dl in the conventional needle lancet group, and there were no significant differences between the two groups (P = 0.940). The pH, CO2 , O2 , lactate and hematocrit levels of the blood were no significant differences between the two groups. In the first trial, the median pain score (interquartile range) of patients using laser lancing device was 2.0 (1.0-3.0), whereas it was 2.5 (2.0-4.0) in patients using a conventional needle lancet (P = 0.029). In the second trial, one week later, the median pain score in the laser lancing device group was 2.5 (1.0-4.0), whereas it was 3.5 (2.25-5.0) in the conventional needle lancet group (P = 0.001). The difference in pain scores between the first and second trials was significant in the conventional needle lancet group (P = 0.007), but not in the laser lancing device group (P = 0.150). Conclusion There was no difference in biochemical results between the laser lancing device group and the conventional needle lancet group. The laser lancing device demonstrated comparatively lower pain than the conventional needle lancet. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Background Although recent studies indicate that the relationship between body mass index (BMI) and Alzheimer's disease (AD) may differ by both sex and age of BMI measurement, little information is available on sex- or age-specific associations between BMI and AD neuropathologies. Objective To examined whether sex-specific BMIs measured at different life-stages (in early adulthood, midlife, and late life) were associated with cerebral amyloid-β (Aβ) deposition and AD-signature region cortical thickness (AD-CT) in cognitively normal (CN) older adults. Methods A total of 212 CN subjects aged 60-90 years (females 108, males 104), who participated in the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study, were included. All participants underwent comprehensive clinical and neuropsychological assessments, [11C] Pittsburgh Compound B positron emission tomography, and brain magnetic resonance imaging. BMIs at different life stages were calculated. Multiple regression analyses were performed separately for either sex. Results In males, lower early adulthood or midlife BMI was associated with greater cerebral Aβ deposition, but late life BMI was not. Lower midlife BMI was associated with reduced AD-CT, but the BMI in early adulthood and late life was not. In females, no significant association was observed between any lifetime BMI and Aβ deposition or AD-CT. Conclusion Our results support a male-specific association between BMI prior to late life, and in vivo AD pathologies. Avoiding underweight status early in life may be important to prevent AD dementia in males, but not females.

OBJECTIVES The aim of this study was to analyze the association between obstructive sleep apnea (OSA) severity and various cardiopulmonary coupling (CPC) parameters in children with OSA. STUDY DESIGN Retrospective cross-sectional study. METHODS A cross-sectional study was conducted among 117 children (aged 7.96 ± 3.54 years, 86 male) who underwent both full-night polysomnography (PSG) and CPC for suspicion of sleep-disordered breathing (SDB). We analyzed the association between various CPC and PSG findings. RESULTS The apnea-hypopnea index (AHI) was negatively correlated with high frequency coupling (HFC, r = -0.374, P

Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer’s disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD., Neuronal sphingosine kinase 1 (SphK1) acetylates COX2 which is needed for microglial phagocytosis activity, and release of pro-resolving mediators (SPMs) from neurons. Here the authors examine how SphK1-mediates COX2 acetylation, and how this leads to increased secretion of SPMs from neurons in the context of Alzheimer’s disease models.

Purpose Although sorafenib as a standard of care for advanced hepatocellular carcinoma (HCC) prolongs overall survival (OS), its efficacy is limited owing to its unsatisfactory objective response and marginal survival benefit. To counter these limitations, we designed a single-arm, phase II trial with liver-directed concurrent chemoradiotherapy (LD-CCRT) and sequential sorafenib treatment in patients with advanced HCC. Methods and Materials We enrolled advanced HCC patients diagnosed between 2014 and 2017 who were ineligible for curative treatment. During the first and last 5 days of 5-week radiation therapy, concurrent hepatic arterial infusion with 5-fluorouracil (500 mg/d) and leucovorin (50 mg/d) through an implanted port was administered 4 weeks after initiation of LD-CCRT and sequential sorafenib treatment (400 mg, twice daily). The primary endpoint was OS. This trial has been registered at clinicaltrials.gov . Results Among the enrolled patients (n = 47), objective response rates 4 weeks after LD-CCRT and during/up to sorafenib maintenance were 44.7% and 53.2%, respectively. Overall, 9 patients (19.1%) underwent curative resection or transplantation after down staging. The median radiation dose was 60 Gy. The median OS was 24.6 months for the entire cohort and 13.0 months for the subgroup with tumor invasion into the main portal trunk or its first branch, whereas the median progression-free survival for the cohort and subgroup was 6.8 and 5.6 months, respectively. The most frequent treatment-related adverse events were diarrhea (36.2%) and hand-foot skin reaction (34%), which were manageable with conservative treatment. Conclusions LD-CCRT and sequential sorafenib treatment provided favorable OS and progression-free survival with good tolerability. Tumor reduction using an initial LD-CCRT enabled down staging, subsequent curative treatment, and long-term survival in about 20% of the patients with advanced HCC. However, further randomized trials are required to confirm these results.

Absorbable wedge-shaped polydioxanone (PDO) sutures are currently available for facial rejuvenation, and they are extremely popular in the aesthetic clinics in Korea. Other than face lifting, threads also can be used for nonsurgical rhinoplasty. The Asian nose is typified by a flat nasal bridge, indistinct nasal dorsum, underprojected and broad nasal tip, and a short columella. In the past, Asian rhinoplasty mainly focused on dorsal augmentation. At present, augmentation of the nasal tip is very popular and is considered an important aspect of achieving a natural and balanced nose.To describe a novel technique with PDO threads in nonsurgical rhinoplasty. In addition, the authors aimed to assess the overall safety and efficacy of nonsurgical rhinoplasty combining both fillers and threads.A retrospective analysis was performed on Korean patients who received rhinoplasty with PDO threads and fillers. All participants underwent a single treatment session. The results were assessed objectively by 2 independent dermatologists using serial photography and subjectively based on the patients' satisfaction scores at 6-month follow-up.A total of 31 patients were evaluated, and 93.5% considered the results satisfactory. Consensus ratings at the 6-month follow-up were largely categorized as very much improved (38.7%), much improved (35.5%), and improved (25.8%). An average increase of 6.3° (percentage increase by 7.6) in the nasolabial angle (p.05) was measured at follow-up. The incidence of the complications was low, and the ones reported were minor.Nonsurgical rhinoplasty combining PDO threads and fillers can be safe and effective, maintaining good results at 6 months after the procedure. Threads are especially useful for lifting-up the nasal tip, contributing to a more harmonious and pleasing nasal appearance by modifying the columella-labial angle.

Background Preoperative chemoradiotherapy (PCRT) followed by surgery and adjuvant chemotherapy is the current standard treatment for stage II/III rectal cancer. However, radiotherapy in the pelvic area is commonly associated with complications such as anastomotic leakage, sexual dysfunction, and fecal incontinence. Recently, the MERCURY study showed that preoperative high-resolution magnetic resonance imaging (MRI) helped to selectively avoid PCRT. It remains unclear whether PCRT is necessary in patients who can achieve a negative circumferential resection margin (CRM) with surgery alone and in patients with cT1–2N1 or cT3N0 without CRM involvement and lateral lymph node metastasis. This study aims to evaluate the efficacy of upfront radical surgery with total mesorectal excision (TME) followed by adjuvant chemotherapy with folinic acid (or leucovorin), fluorouracil, and oxaliplatin (FOLFOX) versus the current standard treatment in patients with surgically resectable, locally advanced rectal cancer. Methods This study, named TME-FOLFOX, is a prospective, open-label, multicenter, phase II randomized trial. Patients with locally advanced rectal cancer will be randomized to receive PCRT followed by TME and adjuvant chemotherapy (arm A) or upfront radical surgery with TME followed by adjuvant FOLFOX chemotherapy (arm B). Clinical stage II/III rectal cancer without CRM involvement and lateral lymph node metastasis will be defined using preoperative MRI. The primary endpoint is 3-year disease-free survival (DFS). Secondary endpoints include 5-year DFS, local recurrence rate, systemic recurrence rate, cost-effectiveness, and overall survival. We hypothesized that our experimental group (arm B) will have a 3-year DFS of 75% and a non-inferiority margin of 15%. Discussion Identifying whether patients require PCRT is one of the critical issues in locally advanced rectal cancer. This study aims to elucidate whether PCRT may not be required for all patients with stage II/III rectal cancer, especially for the MRI-based intermediate-risk group (with cT1–2N1 or cT3N0) without CRM involvement and lateral lymph node metastasis. If the findings indicate that our proposed treatment, which omits PCRT, is non-inferior to the standard treatment, then patients may avoid unnecessary radiation-related toxicity, have a shorter treatment duration, and save on medical costs. Trial registration ClinicalTrials.gov, NCT02167321. Registered on 19 June 2014.

Serum carcinoembryonic antigen (CEA) is a widely used tumor marker in colorectal cancer (CRC), but within normal range of preoperative CEA levels the clinical significance of CEA is unknown. The aim of this study was to evaluate the usefulness of CEA within the normal range as a prognosticator of non-metastatic CRC. This retrospective cohort study included 2021 CRC patients with normal preoperative CEA who underwent elective curative surgery (discovery group). We determined the optimal cut-off value for disease-free survival (DFS) discrimination using the Contal and O’Quigley method. We also assessed the prognostic significance of the cut-off value in a prospective cohort of 171 stage III colon cancer patients treated with oxaliplatin-based adjuvant chemotherapy (validation group). The optimal cut-off CEA value was 2.1 ng/mL in the discovery group. The DFS rates were significantly poorer in patients with high-normal preoperative CEA levels (2.1–5.0 ng/mL) than in those with low-normal CEA levels (

The endoscope-assisted hairline approach is becoming a preferred technique in several surgical disciplines because of its advantage of good cosmetic outcomes. However, such operations are not yet standard for benign lesions in the maxillofacial area due to the anatomical complexity of this region. This study describes an endoscope-assisted technique for resecting benign lesions in the maxillofacial area via a hairline approach. The clinical outcomes with this approach were compared to those obtained with the conventional transcutaneous approach. Benign maxillofacial lesions were excised via endoscope-assisted hairline approach in 27 patients and via transcutaneous approach in 28 patients. Clinical outcomes and complications related to the procedures were evaluated; the primary outcome was the efficacy of the procedure and the secondary outcome was cosmetic satisfaction. There were no significant differences with respect to overall demographic characteristics between the groups, although the operation time was longer for the hairline approach (P=0.001). Cosmetic satisfaction showed much better results for the hairline approach (P=0.001). Endoscope-assisted excision of benign maxillofacial lesions via the hairline approach is a feasible method with excellent cosmetic results.

The aim of our study is to evaluate the clinical efficacy of durvalumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) or polymerase epsilon (POLE)-mutated metastatic or unresectable colorectal cancer (mCRC) who had disease progression after standard chemotherapy. This prospective, open-label, multicenter, phase II study enrolled patients with mCRC harboring MSI-H/dMMR or POLE mutations treated with at least one prior line of therapy. The participants received durvalumab (1500 mg) every 4 weeks intravenously. The primary endpoint was the objective response rate (ORR). Of the 33 patients, 30 had MSI-H/dMMR and 3 had POLE-mutated microsatellite stable (MSS) CRC. With a median follow-up duration of 11.2 months (95% confidence interval [CI]: 7.3-15.0), the ORR was 42.4% (95% CI: 25.5-60.8). Among three patients with POLE-mutated CRC, one patient who had an exonuclease domain mutation (EDM) achieved an objective response, but the others with mutations in the non-exonuclease domain had progressive disease. Overall, the median duration of response was not reached and 85.7% of the responses were ongoing at data cutoff. The progression-free survival rate of 12 months was 58.2% (95% CI: 39.0-73.1) and the 12-month overall survival rate was 68.3% (95% CI: 48.8-81.7). Grade 3 treatment-related adverse events occurred in 36.4% of the patients and were manageable. In conclusion, durvalumab showed promising clinical activity with encouraging response rates and satisfactory survival outcomes in mCRC patients with MSI-H/dMMR or POLE EDM. In patients with POLE-mutated mCRC, clinical response to durvalumab may be restricted to those with EDM.

Objective: This study aimed to evaluate the longitudinal association between changes in depressive symptoms and hazardous drinking among South Korean adults.Participants/Methods: This study was conducted using a sample drawn from participants enrolled in the Korea Welfare Panel Study (KoWePS) from 2013 to 2018. Hazardous drinking was defined as a score of 11 points for men and seven points for women on the Korean version of the Alcohol Use Disorders Identification Test. Depressive symptoms were evaluated using an 11-item version of the Center for Epidemiologic Studies Depression Scale. A generalized estimating equation model was used to analyze the association between changes in depressive symptoms and hazardous drinking.Results: Of the 12,878 people registered with KoWePS and without follow-up losses from 2013 to 2018, a total of 2,341 were included in this study, excluding those under the age of 19 and those with missing data. Persistent depressive symptoms (men, odds ratio [OR]: 2.20, 95% confidence interval [CI]: 1.48–3.21; women, OR: 2.64, 95% CI: 1.66–4.22) and the changes from non-depressive symptoms to depressive symptoms (men, adjusted OR: 2.18, 95% CI: 1.80–2.64; women, OR: 1.71, 95% CI: 1.27–2.29) increased the likelihood of hazardous drinking.Conclusions: Persistent depressive symptoms and changes from non-depressive to depressive symptoms are associated with increased prevalence of hazardous drinking. This suggests that an evaluation of the underlying mental illness or emotion should be made when counseling for abstaining from alcohol for chronic drinkers or the general public.