Sex differences in the relationship between serum total bilirubin and risk of incident metabolic syndrome in community-dwelling adults: Propensity score analysis using longitudinal cohort data over 16 years.

BACKGROUND: Research on identifiable risks for metabolic syndrome (MetS) is ongoing, and growing evidence suggests that bilirubin is a potent antioxidant and cytoprotective agent against MetS. However, there have been conflicting results on the association between bilirubin and MetS. Our study aimed to validate the association by separately stratifying data for men and women in a longitudinal prospective study. METHODS: Data were derived from the Korean Genome Epidemiology Study provided by the Korea Centers for Disease Control and Prevention. Data from 5,185 adults aged 40-69 years (3,089 men and 2,096 women) without MetS were analyzed. The participants were divided according to sex-specific quartiles of serum total bilirubin levels and followed up biennially for 16 years (until 2018). The log-rank test was used for obtaining the Kaplan-Meier curves of cumulative incidence of MetS according to sex-specific serum total bilirubin quartiles, and the hazard ratios (HRs) with 95% confidence intervals (CIs) for incident metabolic syndrome were analyzed with a multiple Cox proportional hazard regression analysis model, after propensity score matching for removing differences at baseline. RESULTS: With increasing serum total bilirubin quartiles, the incidence rate per 1000 person-years proportionally decreased in both men and women. After propensity score matching and adjusting for confounding variables, the HRs (95% CIs) for MetS of the highest quartile in reference to the lowest quartile were 1.00 (0.80-1.24) for men and 0.80 (0.65-0.99) for women. Higher quartiles of serum total bilirubin showed significantly lower cumulative incidence of MetS in women (log-rank test p = 0.009), but not in men (log-rank test p = 0.285). CONCLUSION: Serum total bilirubin levels were significantly inversely associated with MetS in women, but there was no significant association observed in men. Sex differences in the effects of serum total bilirubin should be noted when predicting incident MetS by sex in clinical settings.

Prognostic value of HE4 in advanced-stage, high-grade serous ovarian cancer: Analysis of HE4 kinetics during NACT, predicting surgical outcome and recurrence in comparison to CA125.

OBJECTIVES: To assess the prognostic value of human epididymis protein 4 (HE4) kinetics during and after neoadjuvant chemotherapy (NACT) cycles compared with cancer antigen 125 (CA-125), in predicting the surgical outcomes of interval debulking surgery (IDS) in patients with advanced-stage, high-grade serous ovarian cancer. METHODS: This retrospective cohort study was conducted at Severance Hospital in Seoul, South Korea and involved 123 women with high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who were diagnosed between April 2015 and July 2020. Three outcomes were considered: the chemotherapy response score (CRS) by omentum, residual disease after IDS, and recurrence. Other clinical, imaging, and biological parameters at baseline, during NACT cycles, and pre- and postoperative time were collected and analyzed. RESULTS: We observed a substantial and gradual decrease in both CA-125 level (median from 1612 to 85.55 U/mL; p < 0.001) and HE4 level (514.7 to 87.7 pmol/L; p < 0.001) during NACT cycles, while pre-to-postoperative reduction was only significant for HE4 (median from 77.3 to 62.0 pmol/L (p < 0.001)). Of the total patients, 4.1% showed no response to NACT (chemoresistance) and 65.9% had a partial response. Residual disease was observed in 55 (44.7%) patients. Recurrence occurred in 90 patients (73.2%), with a median progression-free survival of 15.28 months. The percent reduction in CA-125 level- but not HE4 - during NACT was significantly associated with CRS (by omentum); the reduction in CA-125 during NACT cycles was higher when the CRS was found to be 3 and 2 (median = 96.4 [IQR = 8.3] and 93.7 [12.2] respectively) compared to score 1 (68.3 [34.1]), and the difference was statistically significant (p = 0.004). However, no significant association was observed between the percent reduction in CA-125 or HE4 levels during NACT and residual disease or recurrence. The normalization of HE4 - but not CA-125 - before surgery was predictive for surgery outcome; that is, an abnormal preop HE4 level was associated with a residual disease risk ratio of 2.72 (95% CI = 1.27-5.79). CONCLUSION: Monitoring HE4 or CA-125 levels has low prognostic value in patients with advanced-stage, high-grade serous ovarian cancer who are treated with NACT followed by IDS. However, the preoperative level of the HE4 biomarker may be useful in identifying patients at higher risk for suboptimal cytoreductive surgery or who may require more extensive surgery. Further prospective studies are warranted to explore the prognostic utility of eventual combinations of clinical, radiological, and biological parameters, notably by using artificial intelligence-based models.

Frequency of peripheral PD-1+regulatory T cells is associated with treatment responses to PARP inhibitor maintenance in patients with epithelial ovarian cancer.

BACKGROUND: Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis) are becoming the standard of care for epithelial ovarian cancer (EOC). Recently, clinical trials of triple maintenance therapy (PARPi+anti-angiogenic agent+anti-PD-1/L1) are actively ongoing. Here, we investigated the immunological effects of PARPi or triple maintenance therapy on T cells and their impact on clinical responses. METHODS: We collected serial blood from EOC patients receiving PARPi therapy (cohort 1: PARPi, n = 49; cohort 2: olaparib+bevacizumab+pembrolizumab, n = 31). Peripheral T cells were analyzed using flow cytometry and compared according to the PARPi response. Progression-free survival (PFS) was assessed according to prognostic biomarkers identified in a comparative analysis. RESULTS: Regulatory T cells (Tregs) were suppressed by PARPi therapy, whereas PD-1 was not significantly changed. Short PFS group exhibited a higher percentage of baseline PD-1+Tregs than long PFS group, and the patients with high percentage of PD-1+Tregs before treatment showed poor PFS in cohort 1. However, the expression of PD-1 on Tregs significantly decreased after receiving triple maintenance therapy, and the reduction in PD-1+Tregs was associated with superior PFS in cohort 2 (P = 0.0078). CONCLUSION: PARPi suppresses Tregs, but does not affect PD-1 expression. Adding anti-PD-1 to PARPi decreases PD-1+Tregs, which have negative prognostic value for PARPi monotherapy.

Nondestructive volumetric optical analysis of corroded copper oxidation using 1700nm swept-source optical coherence microscopy.

This study presents a novel nondestructive analysis method for precise characterization of corroded copper oxidation using optical coherence microscopy (OCM). By exploiting the partial light transmission through metallic oxide layers, we employed a specialized OCM system with a wavelength of 1700nm and enhanced the analysis accuracy compared to conventional optical coherence tomography (OCT). The developed OCM system featured a numerical aperture (NA) of 0.15, providing improved surface profiling and higher lateral resolution than OCT. we developed a peak-finding algorithm to accurately determine the thickness of the copper oxide layer from the acquired interference data with zero padding. Our method was validated by comparing the measured thickness profiles with those obtained from scanning electron microscope (SEM) images of corroded metals. The copper oxidation specimens were prepared after heat treatment for 1, 2, 4, and 8 h in an alumina tube furnace at a temperature of 900 °C to find the correlation between the OCM thickness measurement. Additionally, the acquired enface 3D images enabled the identification of local corrosion distribution within a 4 mm × 4 mm area. The en-face mapping images are utilized to analyze the uniformity of the metal oxidation process across the imaging area of the copper oxidation specimens. With an increase in heat treatment time, the median value of the thickness histogram for the copper oxide within the area consistently remained around 10 µm. However, the thickness variation ranged from -2 µm to 5 µm. This indicates that as the heat treatment time progresses, the thickness of the copper oxide becomes more non-uniform. Our technique holds great potential for nondestructive and noncontact detection of metal corrosion and assessment of corrosion rates in various industrial applications. Future research efforts could focus on expanding the application of OCM to different metals and exploring its commercialization prospects for practical implementation in diverse industries.

Sex differences in the relationship between platelet count and type 2 diabetes risk in community-dwelling adults: Longitudinal findings over 14 years.

AIMS: Emerging evidence suggests that platelet count predicts the development of type 2 diabetes; however, there is conflicting evidence concerning the relationship in men and women. This study aimed to assess the longitudinal association between platelet count and the incidence risk of type 2 diabetes. MATERIALS AND METHODS: Among 10,030 participants, 7325 participants (3439 men and 3886 women) without diabetes were selected from the Korean Genome and Epidemiology Study. Platelet count quartiles were divided as follows: Q1 ≤219, Q2, 220-254, Q3, 255-296 and Q4 ≥297 (x103 /ml) for men and ≤232, 233-266, 267-305 and ≥306 (x103 /µL) for women. The hazard ratios (HRs) with 95% confidential intervals (CIs) for incident type 2 diabetes were calculated using multiple Cox proportional hazards regression models according to sex-specific platelet count quartiles. RESULTS: During the biennial follow-up period from 2001 to 2002 to 2013-2014, 750 male participants (21.8%, 750/3439) and 730 female participants (18.8%, 730/3886) had newly developed type 2 diabetes. For women, compared to the reference first quartile, the HRs for incident type 2 diabetes in the second, third, and fourth platelet count quartiles were 1.20 (0.96-1.50), 1.21(0.97-1.51), and 1.47 (1.18-1.82) after adjusting for age, body mass index, smoking status, alcohol intake, physical activity, mean arterial blood pressure, family history of diabetes, and HOMA-IR. However, these positive relationships were not observed in men after adjusting for the same co-variables. CONCLUSIONS: Platelet count was independently associated with an increased risk of incident type 2 diabetes only in women.

Rapid combinatorial rewiring of metabolic networks for enhanced poly(3-hydroxybutyrate) production in Corynebacterium glutamicum.

BACKGROUND: The disposal of plastic waste is a major environmental challenge. With recent advances in microbial genetic and metabolic engineering technologies, microbial polyhydroxyalkanoates (PHAs) are being used as next-generation biomaterials to replace petroleum-based synthetic plastics in a sustainable future. However, the relatively high production cost of bioprocesses hinders the production and application of microbial PHAs on an industrial scale. RESULTS: Here, we describe a rapid strategy to rewire metabolic networks in an industrial microorganism, Corynebacterium glutamicum, for the enhanced production of poly(3-hydroxybutyrate) (PHB). A three-gene PHB biosynthetic pathway in Rasltonia eutropha was refactored for high-level gene expression. A fluorescence-based quantification assay for cellular PHB content using BODIPY was devised for the rapid fluorescence-activated cell sorting (FACS)-based screening of a large combinatorial metabolic network library constructed in C. glutamicum. Rewiring metabolic networks across the central carbon metabolism enabled highly efficient production of PHB up to 29% of dry cell weight with the highest cellular PHB productivity ever reported in C. glutamicum using a sole carbon source. CONCLUSIONS: We successfully constructed a heterologous PHB biosynthetic pathway and rapidly optimized metabolic networks across central metabolism in C. glutamicum for enhanced production of PHB using glucose or fructose as a sole carbon source in minimal media. We expect that this FACS-based metabolic rewiring framework will accelerate strain engineering processes for the production of diverse biochemicals and biopolymers.

Analysis of optical propagation characteristics of the ultra-long period grating using RCWA.

There have been significant research and analyses on the diffraction efficiency and characteristics of spectral grating with a wavelength-scale period. However, thus far an analysis on a diffraction grating with an ultra-long pitch over several hundred times of the wavelength (>100µm) and a very deep groove over dozens of micrometers has not been performed. We analyzed the diffraction efficiency of these gratings by using the rigorous coupled-wave analysis (RCWA) method and confirmed that the RCWA analytic results correspond well to the actual experimental results on the wide-angle beam-spreading phenomenon. In addition, because a long-period grating with a deep groove results in a small diffraction angle with relatively uniform efficiency, it is possible to convert a point-like distribution to a linear distribution for a short working distance and a discrete distribution for a very long working distance. We believe that a wide-angle line laser with a long grating period can be used in various applications, such as level detectors, precision measurements, multi-point light detecting and ranging (LiDAR) light sources, and security systems.

Comparison of oncological outcomes between sentinel lymph node biopsy and complete lymphadenectomy for endometrial cancer.

AIM: Sentinel lymph node (SLN) mapping allows node-negative patients to be spared from the surgical comorbidities associated with total lymphadenectomy. This study aimed to evaluate the oncological outcomes of SLN biopsy versus complete lymph node dissection in patients with early-stage endometrial carcinoma. METHODS: Retrospective analyses were performed in patients with pathologically confirmed endometrioid endometrial carcinoma, who underwent minimally invasive surgical staging with SLN biopsy or complete lymph node dissection at Yonsei Cancer Center between 2015 and 2019. RESULTS: A total of 301 patients were included in this study. Eighty-two patients underwent SLN biopsy, while 219 underwent complete lymph node dissection. There were no significant differences in patient characteristics between the two groups. In terms of operative characteristics, the SLN biopsy-only group had a significantly shorter surgical duration (p < 0.001) than the lymphadenectomy group. The mean follow-up period was 41.4 months. There were no differences in progression-free survival (PFS) and overall survival (OS) between the two groups (SLN biopsy vs. complete lymph node dissection; p = 0.798 and 0.301, respectively). Multivariate analysis revealed that SLN biopsy was not an independent prognostic factor for PFS or OS. CONCLUSION: Our results showed that SLN biopsy provided oncological outcomes similar to those of lymphadenectomy.

Fatty liver index as a predictor for incident type 2 diabetes in community-dwelling adults: longitudinal findings over 12 years.

BACKGROUND: Diagnosing fatty liver and identifying disease status are important for fatty liver related-diseases prevention. The fatty liver index (FLI), which can be easily available in clinical practice, can be very useful for managing fatty liver and preventing related diseases. No large-scale and long-term follow-up prospective studies have investigated the relationship between FLI and incident type 2 diabetes (T2DM) independent of baseline insulin resistance status. Therefore, this study aimed to evaluate the association between FLI and incident T2DM and to determine whether FLI could be used as an indicator of T2DM using a large-sample, community-based Korean cohort over 12 years. METHODS: Among the 10,030 total participants, 7,777 (3,676 men and 4,101 women) without diabetes were selected from the Korean Genome and Epidemiology Study (KoGES). FLI grade, which ranged from 0 to 100, was categorized into three groups: low, FLI (< 30); intermediate, FLI (30-59); and high, FLI (≥ 60). The hazard ratios (HRs) with 95% confidence intervals (CIs) for incident T2DM were calculated using multivariate Cox proportional hazards regression models after adjusting for potentially confounding variables. RESULTS: In total, 1,490 individuals (19.2%) developed T2DM during follow-up. Compared to the reference FLI (< 30), the HRs of incident T2DM for the FLI (30-59), and FLI (≥ 60) increased after adjusting for potentially confounding variables, including the HOMA-IR marker. CONCLUSIONS: FLI grade at baseline could be a future indicator of T2DM even when prior glucose or insulin (HOMA-IR) levels are normal.

Incidence of postoperative thrombotic events in ovarian cancer patients with a de-escalated prophylactic strategy: A retrospective cohort study.

OBJECTIVE: This study aimed to determine the incidence of thrombotic events in ovarian cancer patients following a de-escalated prophylactic strategy and to stratify risk groups. METHODS: We reviewed the records of patients who underwent debulking surgery for ovarian cancer at a single institution between January 2007 and May 2019. We identified clinically diagnosed and radiologically confirmed cases of thrombotic events-classified as pulmonary thromboembolism (PE), deep vein thrombosis (DVT), and other thrombotic events-within 6 months of debulking surgery. RESULTS: After excluding 13 patients diagnosed with thromboembolism at the baseline or during neoadjuvant chemotherapy, 799 were analyzed. Since the introduction of medical prophylaxis at our institution in 2009, 482 patients (60%) received medical prophylaxis with subcutaneous injection of low molecular weight heparin for 5 days with mechanical prophylaxis, whereas 317 (40%) received mechanical prophylaxis only. After debulking surgery, thrombotic events occurred in 28 patients (3.5%) including PE (n = 11), DVT (n = 10), and other thrombotic events (n = 7). Multivariable analysis identified age, body mass index (BMI), and operative duration as independent risk factors associated with thrombotic events. A thrombotic event was an independent prognostic factor for overall survival (HR 2.17, 95% CI 1.16-4.1). A cut-off analysis for pre-operative identifiable risk factors showed age < 57 years and BMI < 21 could help define low-risk groups. One patient from 172 low-risk patients (0.58%) experienced a thrombotic event. CONCLUSIONS: The thrombotic event incidence was low in our cohort. A de-escalated prophylaxis strategy may be considered in young (age < 57 years) and lean (BMI < 21) patients.

Usefulness and potential pitfalls of pre-operative PET-CT in patients with endometrial cancer undergoing one- and two-step sentinel lymph node mapping: Do negative findings on PET-CT negativity really indicate node negativity?

OBJECTIVE: We investigated the utility of Positron emission tomography-Computed tomography (PET-CT) in the setting of two different sentinel lymph node (SLN) mapping techniques; the conventional cervical injection method (one-step) and the two-step method, which involves fundal injection followed by cervical injection. METHODS: Patients with endometrial cancer undergoing FDG PET-CT followed by laparoscopic or robotic surgical staging with SLN mapping at the Yonsei Cancer Center between July 2014 and April 2021 were stratified into the PET-positive group (with suspected or likely lymph nodes metastasis) and PET-negative group. A chart review was performed for the number of harvested SLNs, patterns of SLN metastases, and recurrence. RESULTS: Among 466 patients undergoing one-step (n = 276) and two-step (n = 190) SLN mapping, LN metastasis was identified in 21 of 434 PET-negative and 18 of 32 PET-positive patients. The sensitivity and specificity of PET-CT for diagnosing lymph node metastasis were 46.2% and 96.7%, respectively. Among PET-positive patients with LN metastasis, anatomical distribution was concordant in 14/18 patients (77.8%). Among PET-negative patients, four (2.3%) had metastatic para-aortic SLNs, including three (1.7%) with isolated para-aortic metastases; metastatic para-aortic SLNs were exclusively found in the two-step group. Among PET-positive patients, para-aortic SLN metastasis was identified in 35.7% of two-step and 16.7% of one-step group. Among the 21 PET false-negative patients, recurrence was seen in four patients (19%) after a median follow-up of 34 months (range: 7-70 months). CONCLUSIONS: PET-CT served as a useful guide to clinicians with high anatomical concordance rate in patients with LN metastasis. However, despite high specificity, sensitivity was limited. SLN metastasis pattern, especially at the para-aortic level, indicates that the two-step SLN technique might be useful in PET-negative and PET-positive patients.

Vibrio ostreae sp. nov., a novel gut bacterium isolated from a Yellow Sea oyster.

A Gram-stain-negative, oxidase- and catalase-positive, facultative anaerobic motile bacterium, designated strain OG9-811T, was isolated from the gut of an oyster collected in the Yellow Sea, Republic of Korea. The strain grew at 10-37 °C, pH 6.0-9.0 and with 0.5-10% (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain OG9-811T affiliated with the genus Vibrio, with the highest sequence similarity of 98.2% to Vibrio coralliilyticus ATCC BAA-450T followed by Vibrio variabilis R-40492T (98.0 %), Vibrio hepatarius LMG 20362T (97.7 %) and Vibrio neptunius LMG 20536T (97.6 %); other relatives were Vibrio tritonius JCM 16456T (97.4 %), Vibrio fluvialis NBRC 103150T (97.0 %) and Vibrio furnissii CIP 102972T (97.0 %). The complete genome of strain OG9-811T comprised two chromosomes of a total 4 807 684 bp and the G+C content was 50.2 %. Results of analysis based on the whole genome sequence showed the distinctiveness of strain OG9-811T. The average nucleotide identity (ANI) values between strain OG9-811T and the closest strains V. coralliilyticus ATCC BAA-450T, V. variabilis R-40492T, V. hepatarius LMG 20362T, V. neptunius KCTC 12702T , V. tritonius JCM 16456T, V. fluvialis ATCC 33809T and V. furnissi CIP 102972T were 73.0, 72.6, 73.3, 73.0, 72.7, 78.5 and 77.8 %, respectively, while the digital DNA-DNA hybridization values between strain OG9-811T and the above closely related strains were 20.8, 21.2, 20.8, 21.7, 20.7, 23.2 and 22.4 %, respectively. The major fatty acids of strain OG9-811T were summed feature 3 (C16:1 ω7c and/or C16:1 ω6c), summed feature 8 (C18:1 ω6c and/or C18:1 ω7c) and C16:0. The polar lipids contained phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Strain OG9-811T contained Q-8 as a quinone. On the basis of polyphasic taxonomic characteristics, strain OG9-811T is considered to represent a novel species, for which the name Vibrio ostreae sp. nov. is proposed. The type strain is OG9-811T (=KCTC 72623T=GDMCC 1.2610T).

Flavobacterium litorale sp. nov., isolated from red alga.

A Gram-stain-negative and rod-shaped bacterial strain (WSW3-B6T) was isolated from red alga collected from the West Sea, Republic of Korea. Cells of strain WSW3-B6T were non-motile, aerobic and produced slightly yellow and mucoid colonies on marine agar. The strain grew optimally at 23-30 °C, with 0.5-4 % NaCl (w/v) and at pH 6.5-8.5. A phylogenetic analysis of the 16S rRNA gene revealed that strain WSW3-B6T belongs to the genus Flavobacterium within the family Flavobacteriaceae, having the highest sequence similarity to Flavobacterium arcticum SM1502T (96.7%), followed by Flavobacterium salilacus subsp. altitudinum LaA7.5T (96.2%) and Flavobacterium salilacus subsp. salilacus SaA2.12T (96.2%). The complete sequence of a circular chromosome of strain WSW3-B6T determined by combination of Oxford Nanopore and Illumina platforms comprised a total 2 725 095 bp with G+C content of 37.1 mol%. A comparative analysis based on the whole genome also showed the distinctiveness of strain WSW3-B6T. The average nucleotide identity (ANI) values between strain WSW3-B6T and the closest strains F. arcticum SM1502T, F. salilacus subsp. altitudinum LaA7.5T and F. salilacus subsp. salilacus SaA2.12T were 78.3, 77.8 and 77.7 %, respectively, while the digital DNA-DNA hybridization (dDDH) values between strain WSW3-B6T and the above closely related strains were 21.0, 20.4 and 20.3 %, respectively. Both the ANI and dDDH values supported the creation of a new species in the genus Flavobacterium. The major fatty acids (>10 %) were iso-C15 : 0 (19.3 %), C16 : 0 (14.0 %), iso-C17 : 0 3-OH (13.1 %) and C18 : 0 (10.7 %). The polar lipids of strain WSW3-B6T included phosphatidylethanolamine, three unidentified aminolipids and three unidentified lipids. Moreover, MK-6 was the only respiratory quinone. A comparison of the phylogenetic distinctiveness and the unique phenotypic and chemotaxonomic characteristics among strain WSW3-B6T and closely related type strains supported that strain WSW3-B6T (=KCTC 82708T=GDMCC 1.2627T) represents a novel species of the genus Flavobacterium, for which the name Flavobacterium litorale sp. nov. is proposed.

Comparison of triglyceride-glucose index and HOMA-IR for predicting prevalence and incidence of metabolic syndrome.

BACKGROUND AND AIMS: Insulin resistance is related closely to metabolic syndrome (MetS). The homeostasis model assessment of insulin resistance (HOMA-IR) is the most commonly used insulin resistance index, but the triglyceride-glucose (TyG) index has been suggested as a reliable alternative insulin resistance index. This study aims to compare the predictive powers of TyG index and HOMA-IR for the prevalence and incidence of MetS in a large, community-based, prospective cohort over 12 years of follow-up. METHODS AND RESULTS: Data from 9730 adults with or without MetS at baseline, 6091 adults without MetS who were followed as part of the Korean Genome and Epidemiology Study were analyzed. Receiver-operating-characteristic (ROC) curves and time-dependent ROC curves were performed to compare the areas under the ROC curve (AUROC) of the TyG index and HOMA-IR for predicting the prevalence and incidence of MetS. The optimal cut-off points were calculated. Cox proportional hazard spline curves were used to verify dose-response relationship between TyG index/HOMA-IR and incident MetS. TyG index showed higher predictive power for prevalent MetS than HOMA-IR (0.837 vs. 0.680, p < 0.001). The AUROC for incident MetS of TyG index and HOMA-IR was 0.654 (0.644-0.664) and 0.556 (0.531-0.581), respectively (p < 0.001). Cut-off points of TyG index and HOMA-IR for predicting the prevalence of MetS were 8.718 and 1.8 and for predicting incident MetS were 8.518 and 1.5, respectively. Both TyG index and HOMA-IR had a linear relationship with incident MetS. CONCLUSIONS: TyG index is superior to HOMA-IR for predicting MetS.

Long-Term Adverse Effects of Cigarette Smoking on the Incidence Risk of Metabolic Syndrome With a Dose-Response Relationship: Longitudinal Findings of the Korean Genome and Epidemiology Study Over 12 Years.

OBJECTIVE: To investigate the association between the intensity and cumulative dose of cigarette smoking and incidence risk of metabolic syndrome (MetS) in a longitudinal prospective study over 12 years of follow-up. METHODS: This study included 3151 men aged 40 to 69 years from the Korean Genome and Epidemiology Study. MetS was defined as proposed by the Joint Interim Statement of the Circulation 2009 report. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) for incidence risk of MetS were calculated from 2 separate perspectives: (1) number of cigarettes smoked per day (intensity) and (2) total number of cigarettes smoked over a person's lifetime (cumulative dose) using multiple logistic regression analyses. RESULTS: In comparison with never smokers, the HRs (95% CIs) were 0.97 (0.78-1.21) for former smokers and 1.50 (1.07-2.01) with 0 to 9 cigarettes per day, 1.66 (1.34-2.06) with 10 to 19 cigarettes per day, and 1.75 (1.34-2.29) with ≥20 cigarettes per day for current smokers after adjusting for confounding variables. Similar positive dose-response relationships were also observed when the cumulative dose of cigarette smoking was categorized into former and current smokers, with subcategories of <20 and >20 pack-years (PYs). The HRs (95% CIs) were 0.99 (0.77-1.23) for <20 PYs and 0.99 (0.77-1.28) for ≥20 PYs for former smokers and 1.63 (1.32-2.02) for <20 PYs and 1.67 (1.30-2.14) for ≥20 PYs for current smokers after adjusting for the same covariables. CONCLUSION: Cigarette smoking intensity and cumulative dose were both found to be positively associated with the incidence risk of MetS in men.

Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model.

Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats. The objective of this study was to determine metabolomics profiling and biomarkers related to VPA-induced symptoms resembling ASD using proton nuclear magnetic resonance (1H-NMR) spectral data. VPA was administered to pregnant rats at gestation day 12.5 and effects measured subsequently in male 4-week-old offspring pups. The sociability of VPA-treated animals was significantly diminished and exhibited ASD-like behavior as evidenced by reduction of social adaptation disorder and lack of social interactions. To find biomarkers related to ASD, the following were collected prefrontal brain cortices, urine bladder and blood samples directly from heart puncture. In all samples, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) displayed significant clustering pattern differences between control and treated groups. Valine, taurine, myo-inositol, 3-hydroxybutyrate and 1,3-dihydroxyacetone were significantly decreased in brain cortices in treated rats. Serum metabolites of glucose, creatine phosphate, lactate, glutamine and threonine were significantly increased in VPA-administered animals. Urinary metabolites of pimelate, 3-hydroxyisovalerate and valerate were significantly reduced in VPA-treated rat, whereas galactose and galactonate levels were elevated. Various metabolites were associated with mitochondrial dysfunction metabolism and central nervous system disorders. Data demonstrated that VPA-induced alterations in endogenous metabolites of serum, urine, and brain cortex which might prove useful as biomarkers for symptoms resembling ASD as a model of this disorder.

Paludibacterium denitrificans sp. nov., a Novel Denitrifying Bacterium Isolated from Activated Sludge.

A Gram-reaction-negative, facultatively aerobic, motile, non-spore-forming, rod-shaped, and denitrifying bacterium, designated dN18-1T, was isolated from activated sludge, Republic of Korea. This bacterium was investigated via a polyphasic approach to reveal its taxonomic position. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain dN18-1T belongs to the genus Paludibacterium and is most closely related to P. purpuratum KCTC 42852T (96.2% sequence similarity), P. yongneupense KACC 11601T (96.1%), and P. paludis BCRC 80514T (95.2%). The average nucleotide identity values and digital DNA-DNA hybridization values calculated between strain dN18-1T and the closely related strains were 72.5-73.1% and 19.0-19.6%. The genome comprises of 3,347,996 bp with a G + C content of 57.3 mol%. Strain dN18-1T possesses ubiquinone Q-8 as a predominant respiratory quinone, and summed feature 3 (C16:1 ω6c and/or C16:1 ω7c), summed feature 8 (C18:1 ω6c/C18:1 ω7c), C16:0 and C12:0, as its major fatty acids (>5%). The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and four unidentified aminophospholipids. The results of ANI calculation, digital DNA-DNA hybridization, physiological and biochemical tests allowed phenotypic differentiation of strain dN18-1T from rephrase other genus Paludibacterium species with validly published names. Therefore, this isolate represents a novel species, for which the name Paludibacterium denitrificans sp. nov. (type strain dN18-1T = KACC 19537T = CGMCC 1.16961T) is proposed.

Therapeutic Efficacy of Catheter-directed Ethanol Sclerotherapy and Its Impact on Ovarian Reserve in Patients with Ovarian Endometrioma at Risk of Decreased Ovarian Reserve: A Preliminary Study.

STUDY OBJECTIVE: To investigate the therapeutic efficacy of catheter-directed ethanol sclerotherapy (CDS) and its effect on ovarian reserve in patients with endometrioma at risk of decreased ovarian reserve. DESIGN: Retrospective study. SETTING: Teaching hospital. PATIENTS: We evaluated 18 patients with ovarian endometrioma measuring ≥3 cm and preprocedural serum antimüllerian hormone (AMH) levels of <2 ng/mL. INTERVENTIONS: An 8.5-F catheter was inserted either transabdominally or transvaginally into the endometrioma. After aspiration, sclerotherapy with 99% ethanol was performed, with a subsequent 20-minute ethanol retention. MEASUREMENTS AND MAIN RESULTS: Ultrasonography was performed preprocedurally and 6 months after CDS to evaluate any recurrence or changes in cyst size. Furthermore, serum AMH levels, cancer antigen 125 (CA-125) levels, and the visual analog scale scores for dysmenorrhea were obtained to analyze the ovarian reserve and treatment efficacy, preprocedurally and at 6 months after CDS. The mean cyst size on ultrasonography and serum CA-125 levels decreased 6 months after CDS (p <.001 and p = .001, respectively). All patients reported a decreased visual analog scale score for dysmenorrhea (p <.001). However, the difference in serum AMH levels before and after CDS was statistically insignificant (p = .875). CONCLUSION: CDS was efficacious in reducing pain and serum CA-125 levels in patients with low AMH levels without adversely affecting their ovarian reserve.

Development of a novel nannochloropsis strain with enhanced violaxanthin yield for large-scale production.

BACKGROUND: Nannochloropsis is a marine microalga that has been extensively studied. The major carotenoid produced by this group of microalgae is violaxanthin, which exhibits anti-inflammatory, anti-photoaging, and antiproliferative activities. Therefore, it has a wide range of potential applications. However, large-scale production of this pigment has not been much studied, thereby limiting its industrial application. RESULTS: To develop a novel strain producing high amount of violaxanthin, various Nannochloropsis species were isolated from seawater samples and their violaxanthin production potential were compared. Of the strains tested, N. oceanica WS-1 exhibited the highest violaxanthin productivity; to further enhance the violaxanthin yield of WS-1, we performed gamma-ray-mediated random mutagenesis followed by colorimetric screening. As a result, Mutant M1 was selected because of its significant higher violaxanthin content and biomass productivity than WS-1 (5.21 ± 0.33 mg g- 1 and 0.2101 g L- 1 d- 1, respectively). Subsequently, we employed a 10 L-scale bioreactor to confirm the large-scale production potential of M1, and the results indicated a 43.54 % increase in violaxanthin production compared with WS-1. In addition, comparative transcriptomic analysis performed under normal light condition identified possible mechanisms associated with remediating photo-inhibitory damage and other key responses in M1, which seemed to at least partially explain enhanced violaxanthin content and delayed growth. CONCLUSIONS: Nannochloropsis oceanica mutant (M1) with enhanced violaxanthin content was developed and its physiological characteristics were investigated. In addition, enhanced production of violaxanthin was demonstrated in the large-scale cultivation. Key transcriptomic responses that are seemingly associated with different physiological responses of M1 were elucidated under normal light condition, the details of which would guide ongoing efforts to further maximize the industrial potential of violaxanthin producing strains.

Dietary iron to total energy intake ratio and type 2 diabetes incidence in a longitudinal 12-year analysis of the Korean Genome and Epidemiology Cohort Study.

PURPOSE: Recent study found iron consumption has been associated with an increased risk of type 2 diabetes (T2DM). Even though, high iron intake is correlated with total caloric intake, most studies have evaluated the individual effect of iron and total caloric intake. The aim of this study was to investigate the effect of iron intake, in conjunction with total energy intake, on developing T2DM. We also investigated the interactions between dietary iron and energy ratios (IERs) and iron-related single nucleotide polymorphisms (SNPs) in the development of T2DM. METHODS: The study was carried out in Ansan and Ansung, Korea, between March 2001 and December 2014. A total of 6413 participants (3073 men and 3340 women), aged 40-69 years, were enrolled in this study. The mean follow-up period was 8.4 years. The study population was divided into quartiles based on IERs with cut-off points at 4.54, 5.41, and 6.29. The odds ratios (ORs) for new-onset T2DM were calculated across each quartile of IERs and a random forest model was constructed using the default settings to predict new-onset T2DM. To confirm the interaction among IERs, SNPs, and the incidence of T2DM, we measured the predictive power of new-onset T2DM using IER and six SNPs in genes related to iron metabolism [rs855791 (TPMRSS6), rs38116479 (TF), rs1799852 (TF), rs2280673, rs1799945 (HFT), rs180562 (HFE)]. RESULTS: The prevalence of T2DM was 762 (11.8%). IERs showed a positive association with T2DM. The ORs were 1.30 (95% CI 1.02-1.67), 1.20 (95% CI 0.94-1.56), and 1.43 (95% CI 1.11-1.86) across the IER quartiles after adjusting for non-dietary and dietary metabolic risk factors. When the IER was 1.89-fold higher than the reference group, the risk of developing T2DM increased by 43% (OR 1.43; 95% CI 1.11-1.86). CONCLUSION: A higher IER was positively associated with developing T2DM independent of dietary or non-dietary risk factors. We also found the possible interactions between the identified SNPs and iron intake in relations to T2DM.