Proteogenomic analysis of chemo-refractory high-grade serous ovarian cancer.

To improve the understanding of chemo-refractory high-grade serous ovarian cancers (HGSOCs), we characterized the proteogenomic landscape of 242 (refractory and sensitive) HGSOCs, representing one discovery and two validation cohorts across two biospecimen types (formalin-fixed paraffin-embedded and frozen). We identified a 64-protein signature that predicts with high specificity a subset of HGSOCs refractory to initial platinum-based therapy and is validated in two independent patient cohorts. We detected significant association between lack of Ch17 loss of heterozygosity (LOH) and chemo-refractoriness. Based on pathway protein expression, we identified 5 clusters of HGSOC, which validated across two independent patient cohorts and patient-derived xenograft (PDX) models. These clusters may represent different mechanisms of refractoriness and implicate putative therapeutic vulnerabilities.

Characterization of a new CCCTC-binding factor binding site as a dual regulator of Epstein-Barr virus latent infection.

Distinct viral gene expression characterizes Epstein-Barr virus (EBV) infection in EBV-producing marmoset B-cell (B95-8) and EBV-associated gastric carcinoma (SNU719) cell lines. CCCTC-binding factor (CTCF) is a structural chromatin factor that coordinates chromatin interactions in the EBV genome. Chromatin immunoprecipitation followed by sequencing against CTCF revealed 16 CTCF binding sites in the B95-8 and SNU719 EBV genomes. The biological function of one CTCF binding site (S13 locus) located on the BamHI A right transcript (BART) miRNA promoter was elucidated experimentally. Microscale thermophoresis assay showed that CTCF binds more readily to the stable form than the mutant form of the S13 locus. EBV BART miRNA clusters encode 22 miRNAs, whose roles are implicated in EBV-related cancer pathogenesis. The B95-8 EBV genome lacks a 11.8-kb EcoRI C fragment, whereas the SNU719 EBV genome is full-length. ChIP-PCR assay revealed that CTCF, RNA polymerase II, H3K4me3 histone, and H3K9me3 histone were more enriched at S13 and S16 (167-kb) loci in B95-8 than in the SNU719 EBV genome. 4C-Seq and 3C-PCR assays using B95-8 and SNU719 cells showed that the S13 locus was associated with overall EBV genomic loci including 3-kb and 167-kb region in both EBV genomes. We generated mutations in the S13 locus in bacmids with or without the 11.8-kb BART transcript unit (BART(+/-)). The S13 mutation upregulated BART miRNA expression, weakened EBV latency, and reduced EBV infectivity in the presence of EcoRI C fragment. Another 3C-PCR assay using four types of BART(+/-)·S13(wild-type(Wt)/mutant(Mt)) HEK293-EBV cells revealed that the S13 mutation decreased DNA associations between the 167-kb region and 3-kb in the EBV genome. Based on these results, CTCF bound to the S13 locus along with the 11.8-kb EcoRI C fragment is suggested to form an EBV 3-dimensional DNA loop for coordinated EBV BART miRNA expression and infectivity.

Catabolism of 2-keto-3-deoxy-galactonate and the production of its enantiomers.

2-Keto-3-deoxy-galactonate (KDGal) serves as a pivotal metabolic intermediate within both the fungal D-galacturonate pathway, which is integral to pectin catabolism, and the bacterial DeLey-Doudoroff pathway for D-galactose catabolism. The presence of KDGal enantiomers, L-KDGal and D-KDGal, varies across these pathways. Fungal pathways generate L-KDGal through the reduction and dehydration of D-galacturonate, whereas bacterial pathways produce D-KDGal through the oxidation and dehydration of D-galactose. Two distinct catabolic routes further metabolize KDGal: a nonphosphorolytic pathway that employs aldolase and a phosphorolytic pathway involving kinase and aldolase. Recent findings have revealed that L-KDGal, identified in the bacterial catabolism of 3,6-anhydro-L-galactose, a major component of red seaweeds, is also catabolized by Escherichia coli, which is traditionally known to be catabolized by specific fungal species, such as Trichoderma reesei. Furthermore, the potential industrial applications of KDGal and its derivatives, such as pyruvate and D- and L-glyceraldehyde, are underscored by their significant biological functions. This review comprehensively outlines the catabolism of L-KDGal and D-KDGal across different biological systems, highlights stereospecific methods for discriminating between enantiomers, and explores industrial application prospects for producing KDGal enantiomers. KEY POINTS: • KDGal is a metabolic intermediate in fungal and bacterial pathways • Stereospecific enzymes can be used to identify the enantiomeric nature of KDGal • KDGal can be used to induce pectin catabolism or produce functional materials.

Incidence of Clostridioides difficile Infections in Republic of Korea: A Prospective Study With Active Surveillance vs. National Data From Health Insurance Review & Assessment Service.

BACKGROUND: Since the emergence of hypervirulent strains of Clostridioides difficile, the incidence of C. difficile infections (CDI) has increased significantly. METHODS: To assess the incidence of CDI in Korea, we conducted a prospective multicentre observational study from October 2020 to October 2021. Additionally, we calculated the incidence of CDI from mass data obtained from the Health Insurance Review and Assessment Service (HIRA) from 2008 to 2020. RESULTS: In the prospective study with active surveillance, 30,212 patients had diarrhoea and 907 patients were diagnosed with CDI over 1,288,571 patient-days and 193,264 admissions in 18 participating hospitals during 3 months of study period; the CDI per 10,000 patient-days was 7.04 and the CDI per 1,000 admission was 4.69. The incidence of CDI was higher in general hospitals than in tertiary hospitals: 6.38 per 10,000 patient-days (range: 3.25-12.05) and 4.18 per 1,000 admissions (range: 1.92-8.59) in 11 tertiary hospitals, vs. 9.45 per 10,000 patient-days (range: 5.68-13.90) and 6.73 per 1,000 admissions (range: 3.18-15.85) in seven general hospitals. With regard to HIRA data, the incidence of CDI in all hospitals has been increasing over the 13-year-period: from 0.3 to 1.8 per 10,000 patient-days, 0.3 to 1.6 per 1,000 admissions, and 6.9 to 56.9 per 100,000 population, respectively. CONCLUSION: The incidence of CDI in Korea has been gradually increasing, and its recent value is as high as that in the United State and Europe. CDI is underestimated, particularly in general hospitals in Korea.

Manassantin A inhibits tumour growth under hypoxia through the activation of chaperone-mediated autophagy by modulating Hsp90 activity.

BACKGROUND: Chaperon-mediated autophagy (CMA) has taken on a new emphasis in cancer biology. However, the roles of CMA in hypoxic tumours are poorly understood. We investigated the anti-tumour effects of the natural product ManA through the activation of CMA in tumour progression under hypoxia. METHODS: The effect of ManA on CMA activation was assessed in mouse xenograft models and cells. The gene expressions of HIF-1α, HSP90AA1, and transcription factor EB (TFEB) were analysed using The Cancer Genome Atlas (TCGA) datasets to assess the clinical relevance of CMA. RESULTS: ManA activates photoswitchable CMA reporter activity and inhibits Hsp90 chaperone function by disrupting the Hsp90/F1F0-ATP synthase complex. Hsp90 inhibition enhances the interaction between CMA substrates and LAMP-2A and TFEB nuclear localisation, suggesting CMA activation by ManA. ManA-activated CMA retards tumour growth and displays cooperative anti-tumour activity with anti-PD-1 antibody. TCGA datasets show that a combined expression of HSP90AA1High/HIF1AHigh or TFEBLow/HIF1AHigh is strongly correlated with poor prognosis in patients with lung cancer. CONCLUSIONS: ManA-induced CMA activation by modulating Hsp90 under hypoxia induces HIF-1α degradation and reduces tumour growth. Thus, inducing CMA activity by targeting Hsp90 may be a promising therapeutic strategy against hypoxic tumours.

Current practice and recommendations for management of hepatitis B virus in people living with HIV in Asia.

BACKGROUND: The prevalence of HIV and hepatitis B virus (HBV) co-infection is higher in Asia than in Europe and North America and varies significantly between different regions within Asia. Important routes of transmission of both these infections include high-risk unprotected sexual contact, intravenous drug use, and transmission of maternal infection perinatally or in early childhood. While life expectancy among people living with HIV has been extended with effective antiretroviral therapy (ART), HBV-induced liver injury and complications have emerged as a leading cause of morbidity and mortality in people living with HIV. OBJECTIVES: This article describes the prevalence of co-infection, current clinical practice, and recommendations for the management of people living with HIV-HBV co-infection in Asia. RESULTS AND CONCLUSIONS: Screening for HBV should occur at the time of HIV diagnosis; however, HBV screening rates in people living with HIV in Asia vary widely by region. Similarly, people with HBV should be screened for HIV before initiation of HBV antiviral therapy. People with HIV-HBV co-infection should be assessed for liver damage and risk factors for liver disease and be monitored regularly for liver complications and HBV DNA. Medical treatment with ART is lifelong and includes tenofovir and lamivudine or emtricitabine, unless intolerant or contraindicated, as these are active against both HIV and HBV. HBV vaccination programmes are effective in reducing co-infection rates. Mother-to-child transmission can be prevented through measures such as vaccination, antenatal screening, and treatment of pregnant women who are infected.

Changing trends in the incidence and spectrum of cancers between 1990 and 2021 among HIV-infected patients in Busan, Korea.

BACKGROUND: Long-term follow-up data on cancer incidence and spectrum among human immunodeficiency virus (HIV)-infected individuals in Korea have been scarce. MATERIAL AND METHODS: This retrospective cohort study included HIV-infected individuals visiting a tertiary care hospital in Busan, South Korea between 1990 and 2021. The observation was divided into 4 periods. The incidence rate was calculated using direct standardization on age and sex, stratified by calendar period. RESULTS: Of the 1,297 patients, 92 patients (7.1%) were diagnosed with 97 cancers. Excluding 37 patients with prevalent cancer, 1,260 patients were followed for a total of 8,803.7 person-years (PYs), and 55 patients developed 60 incident cancers including 5 second primary incident cancers. In men, the AIDS-defining cancer (ADC) incidence decreased from 294.7 per 100,000 PYs in 1990-1997 to 124.8 per 100,000 PYs in 2014-2021, while the non-AIDS-defining cancer (NADC) incidence increased from 0 per 100,000 PYs to 316.5 per 100,000 PYs during the same period. The proportion of virus-unrelated NADCs (VU-NADCs) increased from 33.3% in 1998-2005 to 49% in 2014-2021. The proportion of human papillomavirus-associated cancers (HPVACs) has recently increased in both ADCs and NADCs. The median time from HIV diagnosis to their first cancer was 1.48 years for ADCs, 6.11 years for VR-NADCs, 8.3 years for VU-NADCs, and 11.5 years for HPVACs. CONCLUSION: The incidence of NADCs is increasing with the aging of HIV-infected patients, and thus, it is necessary to promote cancer screening and prevention programs.

Production of Ethyl-agarobioside, a Novel Skin Moisturizer, by Mimicking the Alcoholysis from the Japanese Sake-Brewing Process.

Agarobiose (AB; d-galactose-ß-1,4-AHG), produced by one-step acid hydrolysis of agarose of red seaweed, is considered a promising cosmetic ingredient due to its skin-moisturizing activity. In this study, the use of AB as a cosmetic ingredient was found to be hampered due to its instability at high temperature and alkaline pH. Therefore, to increase the chemical stability of AB, we devised a novel process to synthesize ethyl-agarobioside (ethyl-AB) from the acid-catalyzed alcoholysis of agarose. This process mimics the generation of ethyl α-glucoside and glyceryl α-glucoside by alcoholysis in the presence of ethanol and glycerol during the traditional Japanese sake-brewing process. Ethyl-AB also showed in vitro skin-moisturizing activity similar to that of AB, but showed higher thermal and pH stability than AB. This is the first report of ethyl-AB, a novel compound produced from red seaweed, as a functional cosmetic ingredient with high chemical stability.

Demonstration of the Yonsei-Social Play Evaluation Tool Keyforms for Occupational Therapy Practice.

Play is regarded as a child's primary occupation and provides valuable information about the child's abilities. Thus, informative assessment tools of play skills are critical for establishing play-related treatment goals in occupational therapy. The objective of this study is to present a practical method for occupational therapists to develop intervention goals using the Yonsei-Social Play Evaluation Tool (Y-SPET) keyforms. Parent responses (n = 310) for preschool children (three to six years old) who did not have a medical diagnosis were examined. The Rasch measurement model was used to create keyforms for the Y-SPET. All children's raw scores were converted into individual Rasch-calibrated logit scores and standard errors were estimated to establish logically attainable treatment goals. Results showed use of the keyforms could logically identify the intervention goals of the children's social play. This suggests that the Y-SPET keyforms are helpful for assessing the level of children's social play and establishing practical treatment goals.

Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation.

OBJECTIVES: To explore extracorporeal membrane oxygenation (ECMO)-related alterations of the pharmacokinetics (PK) of piperacillin/tazobactam and determine an optimal dosage regimen for critically ill adult patients. METHODS: Population PK models for piperacillin/tazobactam were developed using a non-linear mixed effect modelling approach. The percentage of time within 24 h for which the free concentration exceeded the MIC at a steady-state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function were explored using Monte-Carlo simulation. RESULTS: A total of 226 plasma samples from 38 patients were used to develop a population PK model. Piperacillin/tazobactam PK was best described by two-compartment models, in which estimated glomerular filtration rate (eGFR), calculated using CKD-EPI equation based on cystatin C level, was a significant covariate for total clearance of each piperacillin and tazobactam. ECMO use decreased the central volume of distribution of both piperacillin and tazobactam in critically ill patients. Patients with Escherichia coli or Klebsiella pneumoniae infection, but not those with Pseudomonas aeruginosa infection, exhibited a PK/pharmacodynamic target attainment >90% when the target is 50%fT>MIC, as a result of applying the currently recommended dosage regimen. Prolonged or continuous infusion of 16 g/day was required when the treatment goal was 100%fT>MIC or 100%fT>4×MIC, and patients had an eGFR of 130-170 mL/min/1.73 m2. CONCLUSIONS: ECMO use decreases piperacillin/tazobactam exposure. Prolonged or continuous infusion can achieve the treatment target in critically ill patients, particularly when MIC is above 8 mg/L or when patients have an eGFR of 130-170 mL/min/1.73 m2.

Metabolic discrimination of synovial fluid between rheumatoid arthritis and osteoarthritis using gas chromatography/time-of-flight mass spectrometry.

INTRODUCTION: Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. OBJECTIVES: We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. METHODS: We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. RESULTS: We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. CONCLUSION: Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.

Seroprevalence of Helicobacter pylori in human immunodeficiency virus-infected patients in a tertiary care hospital in Busan, South Korea.

INTRODUCTION: Human immunodeficiency virus (HIV) infection management has recently become more successful. While the life expectancy of HIV-infected patients increased, the prevalence of non-acquired immunodeficiency syndrome-defining cancers, such as gastric cancer, also increased. Helicobacter pylori is associated with gastric cancer, the most common cancer and the fourth leading cause of cancer-related deaths in South Korea, which has the highest incidence of chronic gastric mucosa inflammation. Here, the seroprevalence and risk factors of H. pylori infection in Korean HIV-infected patients were evaluated. METHODS: Three hundred HIV-infected patients attending the Outpatient Department of Pusan National University Hospital were prospectively enrolled from October 2018 to February 2019. Socio-demographic information was evaluated using questionnaires, and the serological status of H. pylori infection was analyzed for anti-H. pylori IgG antibodies. RESULTS: The overall seropositivity of H. pylori was 32.7%, and 254 patients (84.7%) were male. The risk factors significantly associated with H. pylori seropositivity were: age of 40-49 years (odds ratio [OR] = 5.00; 95% confidence interval [CI] 1.30-19.17), age of 50-59 years (OR = 3.93; 95% CI 1.05-14.73), CD4 cell counts of 350-500/µL (OR = 4.23; 95% CI 1.53-11.65), CD4 cell counts ≥500/µL (OR = 2.78; 95% CI 1.15-6.72), and a weekly average alcohol consumption of at least one alcoholic beverage (OR = 1.78; 95% CI 1.05-2.99). CONCLUSIONS: The seroprevalence of H. pylori is significantly associated with alcohol consumption, high CD4 cell count, and the age group of 40-59 years.

Dieckol Isolated from Eisenia bicyclis Ameliorates Wrinkling and Improves Skin Hydration via MAPK/AP-1 and TGF-ß/Smad Signaling Pathways in UVB-Irradiated Hairless Mice.

Repetitive exposure to ultraviolet B (UVB) is one of the main causes of skin photoaging. We previously reported that dieckol isolated from Eisenia bicyclis extract has potential anti-photoaging effects in UVB-irradiated Hs68 cells. Here, we aimed to evaluate the anti-photoaging activity of dieckol in a UVB-irradiated hairless mouse model. In this study, hairless mice were exposed to UVB for eight weeks. At the same time, dieckol at two doses (5 or 10 mg/kg) was administered orally three times a week. We found that dieckol suppressed UVB-induced collagen degradation and matrix metalloproteinases (MMPs)-1, -3, and -9 expression by regulating transforming growth factor beta (TGF-ß)/Smad2/3 and mitogen-activated protein kinases (MAPKs)/activator protein-1 (AP-1) signaling. In addition, dieckol rescued the production of hyaluronic acid (HA) and effectively restored the mRNA expression of hyaluronan synthase (HAS)-1/-2 and hyaluronidase (HYAL)-1/-2 in UVB-irradiated hairless mice. We observed a significant reduction in transepidermal water loss (TEWL), epidermal/dermal thickness, and wrinkle formation in hairless mice administered dieckol. Based on these results, we suggest that dieckol, due to its anti-photoaging role, may be used as a nutricosmetic ingredient for improving skin health.

Influence of Vitamin D Deficiency on the Development of Opportunistic Infection in People Living with HIV/AIDS (PWHAs).

BACKGROUND: It is known that vitamin D is associated with immune cell growth, and an association between vitamin D deficiency and development of chronic infections such as tuberculosis has been reported. However, there have been few studies concerning the association between vitamin D deficiency and opportunistic infection (OI) in people living with HIV/AIDS (PWHA). METHOD: PWHAs who had vitamin D (25-OH vitamin D, 25OHD) test results from 2012 to 2017 were enrolled. All enrolled PWHAs were divided into a vitamin D-deficient group and non-deficient group according to the 25OHD cutoff set by ROC curve analysis. The rates of OIs were compared between the two groups. RESULTS: Among 440 enrolled PWHAs, 394 (89.5%) were male, 32 were ≥ 65 years (13.4%), 237 (53.9%) were ART-naïve, and 107 (24.3%) had CD4 + T cell < 200/L. Seventy-three cases of OIs occurred in 63 PWHAs (14.3%); the most common OI was tuberculosis (27, 6.1%) followed by pneumocystis pneumonia (PCP) (25, 5.7%), and Cytomegalovirus (CMV) diseases (10, 2.3%). In the ROC curve analysis, the AUC was 0.71 (95% CI 0.64- 0.79, P < 0.001) and the optimal cutoffs of 25OHD to predict OIs was 14 ng/mL.Overall OI development was significantly more prevalent in the vitamin D-deficiency group (aOR 3.05, 95% CI 1.43-6.48); tuberculosis (aOR 3.51, 95% CI 1.22-10.05) and CMV disease (aOR 10.13, 95% CI 1.11-92.03) were significantly associated with vitamin D deficiency, whereas PCP was not (aOR 1.32, 95% CI 0.44-3.98). CONCLUSION: Stringent cutoffs of vitamin D deficiency (< 14 ng/mL) were well correlated with development of OIs in PWHAs. Vitamin D deficiency was associated with development of OIs, particularly tuberculosis and CMV infections.

Eisenia bicyclis Extract Repairs UVB-Induced Skin Photoaging In Vitro and In Vivo: Photoprotective Effects.

Chronic exposure to ultraviolet B (UVB) is a major cause of skin aging. The aim of the present study was to determine the photoprotective effect of a 30% ethanol extract of Eisenia bicyclis (Kjellman) Setchell (EEB) against UVB-induced skin aging. By treating human dermal fibroblasts (Hs68) with EEB after UVB irradiation, we found that EEB had a cytoprotective effect. EEB treatment significantly decreased UVB-induced matrix metalloproteinase-1 (MMP-1) production by suppressing the activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling and enhancing the protein expression of tissue inhibitors of metalloproteinases (TIMPs). EEB was also found to recover the UVB-induced degradation of pro-collagen by upregulating Smad signaling. Moreover, EEB increased the mRNA expression of filaggrin, involucrin, and loricrin in UVB-irradiated human epidermal keratinocytes (HaCaT). EEB decreased UVB-induced reactive oxygen species (ROS) generation by upregulating glutathione peroxidase 1 (GPx1) and heme oxygenase-1 (HO-1) expression via nuclear factor erythroid-2-related factor 2 (Nrf2) activation in Hs68 cells. In a UVB-induced HR-1 hairless mouse model, the oral administration of EEB mitigated photoaging lesions including wrinkle formation, skin thickness, and skin dryness by downregulating MMP-1 production and upregulating the expression of pro-collagen type I alpha 1 chain (pro-COL1A1). Collectively, our findings revealed that EEB prevents UVB-induced skin damage by regulating MMP-1 and pro-collagen type I production through MAPK/AP-1 and Smad pathways.

Antimicrobial Susceptibility Trends and Risk Factors for Antimicrobial Resistance in Pseudomonas aeruginosa Bacteremia: 12-Year Experience in a Tertiary Hospital in Korea.

BACKGROUND: Infections caused by multidrug-resistant Pseudomonas aeruginosa (MDRPA) have been on the rise worldwide, and delayed active antimicrobial therapy is associated with high mortality. However, few studies have evaluated increases in P. aeruginosa infections with antimicrobial resistance and risk factors for such antimicrobial resistance in Korea. Here, we analyzed changes in antimicrobial susceptibility associated with P. aeruginosa bacteremia and identified risk factors of antimicrobial resistance. METHODS: The medical records of patients with P. aeruginosa bacteremia who were admitted to a tertiary hospital between January 2009 and October 2020 were retrospectively reviewed. Antibiotic resistance rates were compared among the time periods of 2009-2012, 2013-2016, and 2017-2020 and between the intensive care unit (ICU) and non-ICU setting. Empirical antimicrobial therapy was considered concordant, if the organism was susceptible to antibiotics in vitro, and discordant, if resistant. RESULTS: During the study period, 295 patients with P. aeruginosa bacteremia were identified. The hepatobiliary tract (26.8%) was the most common primary site of infection. The rates of carbapenem-resistant P. aeruginosa (CRPA), MDRPA, and extensively drug-resistant P. aeruginosa (XDRPA) were 24.7%, 35.9%, and 15.9%, respectively. XDRPA showed an increasing trend, and CRPA, MDRPA, and XDRPA were also gradually increasing in non-ICU setting. Previous exposure to fluoroquinolones and glycopeptides and urinary tract infection were independent risk factors associated with CRPA, MDRPA, and XDRPA. Previous exposure to carbapenems was an independent risk factor of CRPA. CRPA, MDRPA, and XDRPA were associated with discordant empirical antimicrobial therapy. CONCLUSION: The identification of risk factors for antimicrobial resistance and analysis of antimicrobial susceptibility might be important for concordant empirical antimicrobial therapy in patients with P. aeruginosa bacteremia.

A Prospective Cohort Study of Durations of Staphylococcus aureus Bacteremia According to Different Phenotypes and a New Concept of Persistent Bacteremia.

The purpose of this study was to describe and compare the duration of Staphylococcus aureus bacteremia (SAB) according to methicillin resistance and the primary foci of infection. We also aimed to newly define persistent SAB considering these results. Nonduplicated episodes of SAB in patients aged ≥15 years from 14 hospitals in the Republic of Korea were analyzed between January 2009 and February 2018. The duration of SAB was defined as the number of days from the time of administration of an antibiotic to which the isolate was susceptible after the onset of SAB to the last day of a positive blood culture for S. aureus SAB durations were described and compared based on methicillin resistance and the primary foci of infection. Cases in the top quartile for the duration of bacteremia in the respective clinical context were classified as newly defined persistent SAB, and its association with in-hospital mortality was evaluated. A total of 1,917 cases were analyzed. The duration of SAB was longer in patients with methicillin-resistant SAB (MRSAB; n = 995) than in patients with methicillin-susceptible SAB (MSSAB; n = 922) (median duration, 1 day [interquartile range, 1 to 3 days] for MSSAB and 1 day [interquartile range, 0 to 5 days] for MRSAB; P < 0.001). The duration of bacteremia was longer in patients with endocarditis and bone and joint, endovascular, and surgical site infections and was shorter in patients with skin and soft tissue infections. Newly defined persistent SAB was independently associated with in-hospital mortality (adjusted odds ratio, 1.97; 95% confidence interval, 1.54 to 2.53; P < 0.001). The durations of SAB were dependent on methicillin resistance and the primary foci of infection, and considering these contexts, persistent SAB was significantly associated with in-hospital mortality.

Chemical Constituents from Leaves of Hydrangea serrata and Their Anti-photoaging Effects on UVB-Irradiated Human Fibroblasts.

Hydrangea serrata (THUNB.) SER. (Hydrangeaceae) leaves have been used as herbal teas in Korea and Japan. The objective of this study was to identify anti-photoaging compounds in aqueous EtOH extract prepared from leaves of H. serrata and their effects on UVB-irradiated Hs68 human foreskin fibroblasts. Phytochemical study on H. serrata leaves led to the isolation and characterization of ten compounds: hydrangenol, thunberginol A, thunberginol C, hydrangenoside A, hydrangenoside C, cudrabibenzyl A, 2,3,4'-trihydroxystilbene, thunberginol F, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-galactopyranoside, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-glucopyranoside. Cudrabibenzyl A, 2,3,4'-trihydroxystilbene, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-galactopyranoside, quercetin 3-O-ß-D-xylopyranosyl (1-2)-ß-D-glucopyranoside were firstly isolated from H. serrata. We estimated the effects of 10 compounds on cell viability and production of pro-collagen Type I, matrix metalloproteinase (MMP)-1, and hyaluronic acid (HA) after UVB irradiation. Of these compounds, hydrangenol showed potent preventive activities against reduced cell viability and degradation of pro-collagen Type I in UVB-irradiated Hs68 fibroblasts. Hydrangenol had outstanding inductive activities on HA production. It suppressed mRNA expression levels of MMP-1, MMP-3, hyaluronidase (HYAL)-1, HYAL-2, cyclooxygenase-2 (COX-2), interleukin (IL)-6, IL-8, and IL-1ß in UVB-irradiated Hs68 fibroblasts. When Hs68 fibroblasts were exposed to hydrangenol after UVB irradiation, UVB-induced reactive oxygen species (ROS) production was suppressed. Hydrangenol also inhibited the activation of activator protein-1 (AP-1) and signal transduction and activation of transcription 1 (STAT-1) by downregulating phosphorylation of p38 and extracellular signal-regulated kinase (ERK). Our data indicate that hydrangenol isolated from H. serrata leaves has potential protective effects on UVB-induced skin photoaging.

Preparation and In Vitro Release Studies of Ibuprofen Loaded Nanoparticles Made from PHO and PEGMA-g-PHO.

Monoacrylate-poly(ethylene glycol) grafted poly(3-hydroxyoctanoate) (PEGMA-g-PHO) copolymer was obtained by UV irradiation and ibuprofen (IBU) loaded nanoparticles with PHO or PEGMA-g-PHO polymers were successfully prepared by a single emulsion process. Size of IBU-loaded nanoparticles was about 300 nm based on particle size measurement. Their shapes were spherical. To study drug release properties, IBU release from nanoparticles were performed with FBS buffer. Higher burst release of IBU was observed with the highest graft density of PEGMA groups and 100% drug release was found in 3, 6, and 12 days for PHO, PEGMA-g-PHO0.05, and PEGMA-g-PHO0.15, respectively. Our results suggest that hydrophobic PHO and more hydrophilic PEGMA-g-PHO could be regarded as good candidates of drug release carriers.