Combined effects of smoking and alcohol consumption on the risk of liver cancer according to metabolic syndrome: A nested case-control study in South Korea.

Tobacco and alcohol may interact to increase the risk of liver cancer, which might be modified by other risk factors. Their combined effects in the context of metabolic syndrome (MetS) remain unclear. Given the increasing prevalence of MetS, this nested case-control study was conducted to evaluate the combined effects of smoking and alcohol consumption on liver cancer risk with stratification by MetS. We included 15,352 liver cancer patients and 92,112 matched controls who attended the nationwide general health examination during 2009-2019, using a customized database (N = 5,545,835) from the Korean National Health Insurance Service. Liver cancer risk according to smoking and alcohol consumption was estimated using conditional multivariable logistic regression. Additive and multiplicative interactions between these two factors were assessed. Results showed that in men, dual current users were at a significantly higher risk of liver cancer compared with dual nonusers, adjusted odds ratio (aOR) = 1.61, 95% confidence interval: (1.50, 1.72). Interactions were detected between light-to-moderate alcohol consumption (0.1-28 g/day) and heavy smoking (>20 pack-years) on additive scale, relative excess risk due to interaction = 0.34 (0.16, 0.51), attributable proportion = 0.22 (0.11, 0.33), synergy index = 2.75 (1.85, 3.66), and multiplicative scale, aOR for the product term = 1.28 (1.11, 1.49). An additive interaction was also revealed between light-to-moderate drinking and light-to-moderate smoking in the MetS subgroup. In women, light-to-moderate drinking/nonsmoking was negatively associated with the risk in the non-MetS subgroup. In conclusion, a holistic health promotion program should target male dual users of tobacco cigarettes and alcohol, including light-to-moderate users, especially those with MetS.

Effects of resistance training and nutritional support on osteosarcopenia in older, community-dwelling postmenopausal Korean females (ERTO-K study): a study protocol.

BACKGROUND: Osteosarcopenia is geriatric syndrome defined as the concomitant occurrence of osteopenia/osteoporosis, and sarcopenia. Osteosarcopenia is a relatively new concept in geriatric medicine; however, it may increase the risk of fragility fractures, several morbidities and mortalities, and socioeconomic costs. Although resistance exercises and nutritional support-including protein, calcium, and vitamin D-are potential non-pharmacological management procedures, evidence is still lacking. The objective of this study was therefore to evaluate the effect of combined resistance exercise and nutritional support on the quality and quantity of bone and muscle in postmenopausal females with osteosarcopenia. METHODS: This research proposal presents the protocol for a prospective, single-center, single-blinded, two-armed randomized controlled trial. Thirty-four participants with osteosarcopenia will be recruited and randomly divided into intervention and control groups; both groups will receive nutritional supplements (protein, 40 g; vitamin D, 1600 IU; calcium, 600 mg) daily. The intervention group will undergo 24 weeks of resistance exercise of increasing intensity, achieved through a three-phase step-up process. The primary outcomes will be the changes in skeletal muscle index and bone marrow density of the lumbar spine and femoral neck between the baseline and end of intervention (24 weeks). The secondary outcomes will be the body composition, whole body phase angle, physical function assessment, quality of life, psychological assessment, and bone turnover markers of participants, surveyed at multiple time points. DISCUSSION: This randomized controlled trial may reveal the effect of resistance exercise and nutritional support on older postmenopausal women with osteosarcopenia. The results will provide evidence for developing proper non-pharmacological management guidelines for postmenopausal women. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea, KCT0008291, Registered on 16 March 2023, https://cris.nih.go.kr/cris/search/detailSearch.do/25262 .

The moderating role of circadian gene polymorphisms in the relationship between sleep disturbance and circulating lymphocyte subsets in colorectal cancer patients.

AIM: We investigated the impact of sleep disturbance on immune status in colorectal cancer (CRC) patients with consideration of the moderating role of circadian clock gene polymorphisms. METHODS: A prospective longitudinal study design was used to collect information regarding sleep disturbance. Blood samples for immunologic assays were obtained the day before the first (baseline) and last cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. Clinical sleep disturbance was compared between the two-time points using the Pittsburgh Sleep Quality Index (PSQI) global score. We analysed single-nucleotide polymorphisms in rs2278749, rs3749474, rs2291738, rs17031614, and rs2287161. The dependent variables included changes in the percentages of CD4+, CD8+, CD19+, and CD16/56+ lymphocytes between the two-time points. The results were analysed using moderated regression analysis; the p-values were adjusted using the false discovery rate. RESULTS: Among the 104 patients, no significant dyadic associations were observed between changes in lymphocyte percentages and the PSQI global score. However, the moderated regression analysis revealed five significant associations (rs2287161 with CD8+, rs2278749 and rs2291738 with CD19+, and rs17031614 with CD4+ and CD16/56+ lymphocytes). The inclusion of each interaction resulted in a significant increase (5.7-10.7%) in the variance explained by changes in lymphocyte percentage. CONCLUSION: Patients with specific circadian gene allele types may be more susceptible to immune dysregulation when experiencing sleep disturbances. Considering that sleep disturbance is a modifiable factor that can impact immune regulation, it is essential to prioritise the management of sleep disturbances in CRC patients receiving FOLFOX chemotherapy.

Improvement in Yield of Extracellular Vesicles Derived from Edelweiss Callus Treated with LED Light and Enhancement of Skin Anti-Aging Indicators.

The process of skin aging is currently recognized as a disease, and extracellular vesicles (EVs) are being used to care for it. While various EVs are present in the market, there is a growing need for research on improving skin conditions through microbial and plant-derived EVs. Edelweiss is a medicinal plant and is currently an endangered species. Callus culture is a method used to protect rare medicinal plants, and recently, research on EVs using callus culture has been underway. In this study, the researchers used LED light to increase the productivity of Edelweiss EVs and confirmed that productivity was enhanced by LED exposure. Additionally, improvements in skin anti-aging indicators were observed. Notably, M-LED significantly elevated callus fresh and dry weight, with a DW/FW ratio of 4.11%, indicating enhanced proliferation. Furthermore, M-LED boosted secondary metabolite production, including a 20% increase in total flavonoids and phenolics. The study explores the influence of M-LED on EV production, revealing a 2.6-fold increase in concentration compared to darkness. This effect is consistent across different plant species (Centella asiatica, Panax ginseng), demonstrating the universality of the phenomenon. M-LED-treated EVs exhibit a concentration-dependent inhibition of reactive oxygen species (ROS) production, surpassing dark-cultured EVs. Extracellular melanin content analysis reveals M-LED-cultured EVs' efficacy in reducing melanin production. Additionally, the expression of key skin proteins (FLG, AQP3, COL1) is significantly higher in fibroblasts treated with M-LED-cultured EVs. These results are expected to provide valuable insights into research on improving the productivity of plant-derived EVs and enhancing skin treatment using plant-derived EVs.

Statement by the Korean Society of Occupational and Environmental Medicine on the proposed reform of working hours in South Korea.

The current 52-hour workweek in South Korea consists of 40 hours of regular work and 12 hours of overtime. Although the average working hours in South Korea is declining, it is still 199 hours longer than the Organisation for Economic Co-operation and Development average of 1,716 hours per year. In view to this, the South Korean government has now proposed to reform the workweek, mainly intending to increase the workweek to 69 hours when the workload is heavy. This reform, by increasing the labor intensity due to long working hours, goes against the global trend of reducing work hours for a safe and healthy working environment. Long working hours can lead to increased cerebrovascular and cardiovascular diseases, industrial accidents, mental health problems, and safety accidents due to lack of concentration. In conclusion, the Korean government's working hour reform plan can have a negative impact on workers' health, and therefore it should be thoroughly reviewed and modified.

Weight maintenance and gain were significantly associated with lower risk of all-cause and cancer-related mortality in Korean adults who were newly diagnosed with cancer based on the Korean NHIS-HEALS cohort.

The burden of malignant neoplasms is increasing worldwide. Healthy lifestyles such as maintaining a healthy body weight are important to improve survival rate in cancer patients. This study was aimed to test the hypothesis that weight change affects mortality in patients newly diagnosed with cancer. This study was retrospectively designed based on the National Health Insurance Service-National Health Screening Cohort. A total of 1856 subjects aged at least 40 years who received a national health checkup within 6 months before cancer diagnosis was included. Study subjects were classified into 3 categories based on weight change before and after cancer diagnosis: weight loss, maintenance, and gain. Cox proportional hazards regression models were adopted to examine the association between weight change and mortality after adjusting for confounders. Compared to those experiencing weight loss, the adjusted hazards ratios (HRs) (95% confidence intervals [CIs]) for those experiencing weight maintenance were 0.327 (0.189-0.568) for all-cause mortality and 0.431 (0.215-0.867) for cancer-related mortality. The adjusted HRs (95% CIs) for those experiencing weight gain were 0.149 (0.044-0.505) for all-cause mortality and 0.289 (0.080-1.045) for cancer-related mortality. After stratifying according to baseline body mass index (BMI), weight maintenance and gain were negatively associated with all-cause mortality (0.286 [0.138-0.592] for weight maintenance and 0.119 [0.027-0.533] for weight gain) among those with a BMI < 25 kg/m2. Weight maintenance and gain reduced the risk of all-cause mortality in patients newly diagnosed with any cancer. In addition, weight maintenance was significantly related to cancer-related mortality.

The Protective Effects of Moisturizer Containing Potentilla anserina Extract in the Topical Treatment of Skin Damage Caused by Masks.

The use of face masks during the COVID-19 pandemic resulted in significant societal changes, particularly for individuals with sensitive skin. To address this issue, the researchers explored traditional medicine and identified Potentilla anserina extract as a potential solution due to its anti-inflammatory and moisturizing effects. This research investigated how this extract influences skin hydration, barrier function, and itching. The findings revealed that the extract had a hydrating effect by elevating Aquaporin-3 (AQP3) expression. Additionally, the study demonstrated that the extract improved skin barrier function, with Filaggrin (FLG) expression being approximately three times higher (p < 0.001) in the Potentilla-anserina-extract-treated group compared to the control group and the genes associated with itching being reduced. In this process, we researched and developed HPßCD (hydroxypropyl-ß-cyclodextrin)-Liposome containing Potentilla anserina extract, gradually and sustainably releasing the active components of the Potentilla anserina extract. During four weeks of clinical trials involving individuals wearing masks for over 6 h a day, a moisturizer containing Potentilla anserina extract demonstrated a notable reduction in skin redness. Hemoglobin values (A.U.), which serve as indicators of skin redness, showed decreases of 5.06% and 6.74% in the test area inside the mask after 2 and 4 weeks, respectively, compared to the baseline measurements. Additionally, the moisturizer containing Potentilla anserina extract notably decreased Trans Epidermal Water Loss (TEWL), with reductions of 5.23% and 9.13% observed in the test area inside the mask after 2 and 4 weeks, respectively. The moisturizer, especially in the test area treated with the extract-containing moisturizer, significantly enhanced skin hydration compared to the control group. The Corneometer values (A.U) exhibited notable increases of 11.51% and 15.14% in the test area inside the mask after 2 and 4 weeks, respectively. These discoveries emphasize the potential of Potentilla anserina extract and its utility in tackling skin issues caused by mask wearing, including enhancing moisture, fortifying the skin's barrier, and alleviating itching. These results indicate that moisturizers incorporating specific ingredients provide greater benefits compared to conventional moisturizers.

Anti-Inflammatory Effects and Macrophage Activation Induced by Bioavailable Cinnamon Polyphenols in Mice.

SCOPE: Cinnamon is a commonly used spice and herb that is rich in polyphenols. Due to the limited bioavailability of oral polyphenols, it remains unclear to which extent they can reach cells and exert a biological effect. This study aims to investigate the impact of bioavailable cinnamon polyphenols on lipopolysaccharide (LPS)-stimulated macrophages. METHODS AND RESULTS: A polyphenol fraction is prepared from cinnamon (Cinnamomi ramulus) (CRPF) by boiling cinnamon in water and adsorbing the extract onto a hydrophobic resin. Mice are orally administered CRPF for 7 days and then subjected to three independent experiments: endotoxemia, serum collection, and macrophage isolation. Upon intraperitoneal lipopolysaccharide challenge, CRPF decreases serum levels of inflammatory cytokines, involving suppression of liver and spleen macrophages. When normal macrophages are cultured in serum obtained from CRPF-treated mice, they exhibit an anti-inflammatory phenotype. However, macrophages from CRPF-treated mice show an increased production of inflammatory cytokines when cultured in fetal bovine serum and stimulated with LPS. CONCLUSION: The study provides evidence for the presence of bioavailable cinnamon polyphenols with anti-inflammatory properties and macrophage activation. These findings suggest that cinnamon polyphenols have the potential to modulate macrophage function, which could have implications for reducing inflammation and improving immune function.

First report of konjac mosaic virus in Spuriopimpinella brachycarpa in Korea.

Spuriopimpinella brachycarpa Nakai (Common name, Chamnamul; family Apiaceae) is a plant whose leaves are consumed as a vegetable and used as a folk medicine in Korea (Kim et al., 2020). In February 2020, seven samples of S. brachycarpa leaf showing virus symptoms including yellowing, vein chlorosis, chlorotic lesions, and severe mottling were collected from a greenhouse in Busan, South Korea, to diagnose the potential disease (Fig. S1a, b). The disease incidence rate in the greenhouse was >10% (2,970 m2). To identify the causal virus, we analyzed leaf dip preparation and thin sections of the symptomatic leaves by transmission electron microscopy. Filamentous virus particles and pinwheel structures were observed, indicating the presence of a potyvirus (Fig. S1c, d). To confirm these results, the symptomatic leaf samples were further analyzed by reverse-transcription polymerase chain reaction (RT-PCR) using potyvirus universal primers (Table S2) and direct sequencing of the PCR products. All samples were positive for konjac mosaic virus (KoMV). To exclude the possibility of infection by multiple viruses, we performed high-throughput sequencing (HTS) on an Illumina NovaSeq 6000 system (Macrogen Inc., Seoul, South Korea). There were two contigs (9,267 and 2,851 nt) mapping to KoMV sequences. A large contig (9,267 nt; 705,967 mapped reads; mean read coverage of 11,351.4x) showed about 80% identity (93% coverage) with KoMV-F (GenBank accession no. NC_007913) isolated from Amorphophallus konjac in Japan (Nishiguchi et al., 2006). To isolate KoMV from S. brachycarpa, we mechanically inoculated leaf extracts from symptomatic samples onto Chenopodium quinoa as an assay host via three single-lesion passages, followed by propagation in Nicotiana benthamiana. In a bioassay of the KoMV isolate (KoMV-BS), we mechanically inoculated sap from infected N. benthamiana onto 31 indicator plants including Cryptotaenia japonica (Apiaceae), which is similar to S. brachycarpa (Table S3). KoMV-BS systemically induced vein chlorosis and/or leaf mottling in four Nicotiana species and C. japonica, and chlorotic local lesions in upper leaves of C. quinoa; no symptoms were observed in 25 other indicator plants. These results were confirmed by RT-PCR. Next, we obtained the complete genome sequence of KoMV-BS using HTS and 5' and 3' rapid amplification of cDNA ends, with newly designed primers (Table S2). The assembled full-length KoMV-BS genome sequence was 9,392 nt in length, excluding the poly(A) tail, and encoded a polyprotein composed of 3,060 amino acids. The sequence was deposited in GenBank (accession no. OR001914). BLAST analysis showed 84~88% and 90~98% identities at CP nucleotide and amino acid levels, respectively with the reported KoMV isolates, confirming the virus to be an isolate of KoMV (synonym; Japanese hornwort mosaic virus, zantedeschia mosaic virus) (Adams et al., 2005; Nishiguchi et al., 2006). KoMV infection was first reported in A. konjac from Japan (Shimoyama et al. 1992) and has been spread worldwide as one of the major causal agents of viral diseases in calla lily (Liao et al., 2020). To the best of our knowledge, this is the first report of KoMV infection in S. brachycarpa. To date, cucumber mosaic virus and tobacco mosaic virus have been reported to infect S. brachycarpa in Korea (Yoon et al., 2016; 2017). Our findings will be helpful for developing virus-management strategies to prevent yield and quality loss in S. brachycarpa.

Association between polycythemia and risk of ischemic stroke in males based on the national health insurance service-health screening cohort.

BACKGROUND: Polycythemia, a state in which the hematocrit or hemoglobin (Hb) concentration in the peripheral blood increases, is associated with several thrombosis-related diseases, of which cerebral infarction is relatively common. This study aimed to investigate the association between ischemic stroke and polycythemia, as a potential risk factor. RESEARCH DESIGN AND METHODS: This study included men who had undergone national health checkups between 2002 and 2003; the data were extracted from the Korean National Health Insurance Service-Health Screening database. The primary outcome was the risk ischemic stroke; adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for ischemic stroke were calculated using Cox proportional hazards regression models. RESULTS: In total, 207,737 male participants aged 40-79 years were included in this study. At the baseline, 13972 (6.7%) participants met the polycythemia criteria (Hb >16.5 g/dL). During the study period, 897 and 12,440 cases of ischemic stroke occurred in the polycythemia and normocythemia (13.0 g/dL ≤ Hb ≤16.5 g/dL) groups, respectively. Compared with the normocythemia group, the polycythemia group showed an adjusted HR (95% CI) for ischemic stroke of 1.12 (1.04-1.20). CONCLUSIONS: The risk of ischemic stroke was higher in participants with polycythemia than in those with normocythemia.

Mineral bone disorder in children with chronic kidney disease: Data from the KNOW-Ped CKD (Korean cohort study for outcome in patients with pediatric chronic kidney disease) study.

Background: Children with chronic kidney disease (CKD) are at high risk of mineral bone disorder (MBD), which leads to fractures, growth retardation, and cardiovascular disease. We aimed to comprehensively understand the relationship between renal function and factors related to MBD and evaluate the prevalence and distribution characteristics of MBD, specifically among Korean patients from the KNOW-PedCKD cohort. Methods: From the baseline data of the KNOW-PedCKD cohort, we examined the prevalence and distribution of MBD in 431 Korean pediatric CKD patients, including the level of corrected total calcium, serum phosphate, serum alkaline phosphatase, serum intact parathyroid hormone (iPTH), fibroblast growth factor 23 (FGF-23), serum vitamin D, fractional excretion of phosphate (FEP), and bone densitometry Z-scores. Results: The median serum calcium level remained relatively normal regardless of the CKD stage. The levels of 1,25-dihydroxy vitamin D, urine calcium-to-creatinine ratio, and bone densitometry Z-score significantly decreased with advancing CKD stage, while those of serum phosphate, FGF-23, and FEP significantly increased with CKD stage. The prevalence of hyperphosphatemia (17.4%, 23.7%, and 41.2% from CKD stages 3b, 4, and 5, respectively) and hyperparathyroidism (37.3%, 57.4%, 55.3%, and 52.9% from CKD stages 3a, 3b, 4, and 5, respectively) significantly increased with the CKD stage. Prescriptions of medications, such as calcium supplements (39.1%, 42.1%, 82.4%), phosphate binders (39.1%, 43.4%, 82.4%), and active vitamin D (21.7%, 44.7%, and 64.7%) significantly increased with CKD stage 3b, 4, and 5, respectively. Conclusions: The results demonstrated the prevalence and relationship of abnormal mineral metabolism and bone growth according to CKD stage in Korean pediatric CKD patients for the first time.

Long-term outcome of Bartter syndrome in 54 patients: A multicenter study in Korea.

Introduction: Bartter syndrome (BS) is a rare salt-wasting tubulopathy caused by mutations in genes encoding sodium, potassium, or chloride transporters of the thick ascending limb of the loop of Henle and/or the distal convoluted tubule of the kidney. BS is characterized by polyuria, failure to thrive, hypokalemia, metabolic alkalosis, hyperreninemia, and hyperaldosteronism. Potassium and/or sodium supplements, potassium-sparing diuretics, and nonsteroidal anti-inflammatory drugs can be used to treat BS. While its symptoms and initial management are relatively well known, long-term outcomes and treatments are scarce. Methods: We retrospectively reviewed 54 Korean patients who were clinically or genetically diagnosed with BS from seven centers in Korea. Results: All patients included in this study were clinically or genetically diagnosed with BS at a median age of 5 (range, 0-271) months, and their median follow-up was 8 (range, 0.5-27) years. Genetic diagnosis of BS was confirmed in 39 patients: 4 had SLC12A1 gene mutations, 1 had KCNJ1 gene mutations, 33 had CLCNKB gene mutations, and 1 had BSND mutation. Potassium chloride supplements and potassium-sparing diuretics were administered in 94% and 68% of patients, respectively. The mean dosage of potassium chloride supplements was 5.0 and 2.1 mEq/day/kg for patients younger and older than 18 years, respectively. Nephrocalcinosis was a common finding of BS, and it also improved with age in some patients. At the last follow-up of 8 years after the initial diagnosis, 41% had short stature (height less than 3rd percentile) and impaired kidney function was observed in six patients [chronic kidney disease (CKD) G3, n = 4; CKD G5, n = 2]. Conclusion: BS patients require a large amount of potassium supplementation along with potassium-sparing agents throughout their lives, but tend to improve with age. Despite management, a significant portion of this population exhibited growth impairment, while 11% developed CKD G3-G5.

Effect of water filtration infrared-A (wIRA) sauna on inorganic ions excreted through sweat from the human body.

Sweat discharged as a result of exposure to sauna plays an important role in removing inorganic ions accumulated in the body, including heavy metals. In this study, inorganic ions (toxic and nutrient elements) excreted in the form of sweat from the body using a water-filtered infrared-A (wIRA) sauna were determined using inductively coupled plasma sector field mass spectrometry. The analyzed elements included eight toxic elements (Al, As, Be, Cd, Ni, Pb, Ti, and Hg) and 10 nutrient elements (Ca, Co, Cr, Cu, Fe, Mg, Mn, Se, V, and Zn), and their correlations were determined. Analysis of the sweat obtained from 22 people using the wIRA sauna showed a higher inorganic ion concentration than that obtained from conventional activities, such as exercise or the use of wet sauna, and the concentration of toxic elements in sweat was higher in females than in males. Correlation analysis of the ions revealed a correlation between the discharge of toxic elements, such as As, Be, Cd, and Ni, and discharge of Se and V, and Ni was only correlated with Mn. This study provides fundamental information on nutritional element supplementation when using wIRA sauna for detoxification.

Electroacupuncture for the treatment of frozen shoulder: A systematic review and meta-analysis.

Background: Electroacupuncture (EA) has reportedly been successful in controlling pain, but there have been no systematic reviews examining the impact of EA on patients with frozen shoulder (FS). The purpose of this review is to provide evidence on the safety and efficacy of EA for pain management in patients with FS. Methods: We searched 11 databases from their inception: EMBASE, the Cochrane Library, PubMed, AMED, one Chinese medical database, and six Korean medical databases. Two researchers independently performed the study selection, data extraction, and assessment. Bias-related risk was evaluated using the Cochrane risk-of-bias assessment tool. Results: This review included thirteen studies involving 936 patients. The EA group exhibited improvements in FS pain (MD -1.11, 95% CI -1.61 to -0.61, p < 0.0001, I 2 = 97%), function (SMD 2.02, 95% CI 0.36-3.69, p < 0.00001, I 2 = 97%), and response rates (RR 1.16, 95% CI 1.07-1.25; p = 0.0002; I 2 = 0%) over the manual acupuncture (MA) group. As an adjunct treatment, EA improved FS pain (SMD -1.12, 95% CI -1.52 to -0.71, P < 0.00001, I 2 = 0) compared to the control treatments. No adverse effects were reported. Conclusion: EA is reported to improve FS pain and function compared with control treatments. Additionally, EA can be used as an adjunct therapy for FS pain. EA could emerge as a potent intervention against FS. Systematic review registration: [http://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021247090], identifier [CRD42021247090].

Pharmacokinetic Comparison of Chitosan-Derived and Biofermentation-Derived Glucosamine in Nutritional Supplement for Bone Health.

Glucosamine and chondroitin sulfate have been used as nutritional supplementation for joint tissues and osteoarthritis (OA). Biofermented glucosamine is of great interest in the supplement industry as an alternative source of glucosamine. The purpose of this study is to compare the pharmacokinetics of chitosan-derived glucosamine and biofermentation-derived glucosamine as nutritional supplementation. In a randomized, double-blind and cross-over study design, we recruited subjects of healthy men and women. The pharmacokinetics of glucosamine were examined after a single dose of glucosamine sulfate 2KCl (1500 mg) with two different sources of glucosamine (chitosan-derived glucosamine and biofermentation-derived glucosamine) to male and female subjects fitted with intravenous (iv) catheters for repeated blood sampling up to 8 h. According to plasma concentration-time curve of glucosamine after an oral administration of 1500 mg of glucosamine sulfate 2KCl, AUC0-8h and AUC0-∞ values of glucosamine following oral administration of chitosan-derived and biofermentation-derived glucosamine formulations were within the bioequivalence criteria (90% CI of ratios are within 0.8-1.25). The mean Cmax ratios for these two formulations (90% CI of 0.892-1.342) did not meet bioequivalence criteria due to high within-subject variability. There were no statistically significant effects of sequence, period, origin of glucosamine on pharmacokinetic parameters of glucosamine such as AUC0-8h, AUC0-∞, Cmax. Our findings suggest that biofermentation-derived glucosamine could be a sustainable source of raw materials for glucosamine supplement.

Cohort Profile: Korean Tuberculosis and Post-Tuberculosis Cohort Constructed by Linking the Korean National Tuberculosis Surveillance System and National Health Information Database.

We aimed to review the current data composition of the Korean Tuberculosis and Post-Tuberculosis Cohort, which was constructed by linking the Korean Tuberculosis Surveillance System (KNTSS; established and operated by the Korean Disease Control and Prevention Agency since 2000) and the National Health Information Database (NHID; established by the National Health Insurance Service in 2012). The following data were linked: KNTSS data pertaining to patients diagnosed with tuberculosis between 2011 and 2018, NHID data of patients with a history of tuberculosis and related diseases between 2006 and 2018, and data (obtained from the Statistics Korea database) on causes of death. Data from 300 117 tuberculosis patients (177 206 men and 122 911 women) were linked. The rate of treatment success for new cases was highest in 2015 (86.7%), with a gradual decrease thereafter. The treatment success rate for previously treated cases showed an increasing trend until 2014 (79.0%) and decreased thereafter. In total, 53 906 deaths were confirmed among tuberculosis patients included in the cohort. The Korean Tuberculosis and Post-Tuberculosis Cohort can be used to analyze different measurement variables in an integrated manner depending on the data source. Therefore, these cohort data can be used in future epidemiological studies and research on policy-effect analysis, treatment outcome analysis, and health-related behaviors such as treatment discontinuation.

Effect of Factor H on Complement Alternative Pathway Activation in Human Serum Remains on Porcine Cells Lacking N-Glycolylneuraminic Acid.

Background: Triple knockout (TKO) donor pigs lacking alpha-1,3-galactose (Gal), N-glycolylneuraminic acid (Neu5Gc), and Sd(a) expressions were developed to improve the clinical success of xenotransplantation. Neu5Gc, a sialic acid expressed on cell surfaces, recruits factor H to protect cells from attack by the complement system. Lack of Neu5Gc expression may cause unwanted complement activation, abrogating the potential benefit of gene-modified donor pigs. To investigate whether TKO porcine cells display increased susceptibility to complement activation in human serum, pathway-specific complement activation, apoptosis, and human platelet aggregation by porcine cells were compared between alpha-1,3-galactosyltransferase gene-knockout (GTKO) and TKO porcine cells. Methods: Primary porcine peripheral blood mononuclear cells (pPBMCs) and endothelial cells (pECs) from GTKO and TKO pigs were used. Cells were incubated in human serum diluted in gelatin veronal buffer (GVB++) or Mg++-EGTA GVB, and C3 deposition and apoptotic changes in these cells were measured by flow cytometry. C3 deposition levels were also measured after incubating these cells in 10% human serum supplemented with human factor H. Platelet aggregation in human platelet-rich plasma containing GTKO or TKO pECs was analyzed. Results: The C3 deposition level in GTKO pPBMCs or pECs in GVB++ was significantly higher than that of TKO pPBMCs or pECs, respectively, but C3 deposition levels in Mg++-EGTA-GVB were comparable between them. The addition of factor H into the porcine cell suspension in 10% serum in Mg++ -EGTA-GVB inhibited C3 deposition in a dose-dependent manner, and the extent of inhibition by factor H was similar between GTKO and TKO porcine cells. The percentage of late apoptotic cells in porcine cell suspension in GVB++ increased with the addition of human serum, of which the net increase was significantly less in TKO pPBMCs than in GTKO pPBMCs. Finally, the lag time of platelet aggregation in recalcified human plasma was significantly prolonged in the presence of TKO pECs compared to that in the presence of GTKO pECs. Conclusion: TKO genetic modification protects porcine cells from serum-induced complement activation and apoptotic changes, and delays recalcification-induced human platelet aggregation. It does not hamper factor H recruitment on cell surfaces, allowing the suppression of alternative complement pathway activation.

Recent trends in opioid prescriptions in Korea from 2002 to 2015 based on the Korean NHIS-NSC cohort.

OBJECTIVES: Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. METHODS: The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). RESULTS: The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. CONCLUSIONS: Consumption of opioids greatly increased in Korea over the 14-year study period.