A dual gene-specific mutator system installs all transition mutations at similar frequencies in vivo.

Targeted in vivo hypermutation accelerates directed evolution of proteins through concurrent DNA diversification and selection. Although systems employing a fusion protein of a nucleobase deaminase and T7 RNA polymerase present gene-specific targeting, their mutational spectra have been limited to exclusive or dominant C:G→T:A mutations. Here we describe eMutaT7transition, a new gene-specific hypermutation system, that installs all transition mutations (C:G→T:A and A:T→G:C) at comparable frequencies. By using two mutator proteins in which two efficient deaminases, PmCDA1 and TadA-8e, are separately fused to T7 RNA polymerase, we obtained similar numbers of C:G→T:A and A:T→G:C substitutions at a sufficiently high frequency (∼6.7 substitutions in 1.3 kb gene during 80-h in vivo mutagenesis). Through eMutaT7transition-mediated TEM-1 evolution for antibiotic resistance, we generated many mutations found in clinical isolates. Overall, with a high mutation frequency and wider mutational spectrum, eMutaT7transition is a potential first-line method for gene-specific in vivo hypermutation.

Quantitative Analysis and Molecular Docking Simulation of Flavonols from Eruca sativa Mill. and Their Effect on Skin Barrier Function.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents, including n-hexane (EHex), chloroform (ECHCl3), ethyl acetate (EEA), n-butyl alcohol (EBuOH), and water (EDW). Ethyl acetate fraction (EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines (IL-6 and TNF-α) in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-and di-glycoside of each aglycone. The main flavonol form of EEA is the mono-glycoside of each aglycone detected, and the most abundant flavonol mono-glycoside is kaempferol 3-glucoside 7.4%, followed by quercetin-3-glucoside 2.3% and isorhamnetin 3-glucoside 1.4%. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that the flavonol composition of E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Comparative effectiveness of tofacitinib and tumour necrosis factor inhibitors in patients with rheumatoid arthritis in real-world practice: a prospective observational study.

OBJECTIVE: To assess the effectiveness of tofacitinib vs tumour necrosis factor inhibitors (TNFi) in Korean patients with rheumatoid arthritis (RA). METHODS: The study used data from a single academic referral hospital's registries of biologic disease-modifying anti-rheumatic drugs (bDMARDs) and tofacitinib and examined remission rates based on the disease activity score (DAS)28-erythrocyte sedimentation rate (ESR) after 12 months. Multivariable logistic regression analysis was used to estimate the odds ratio (OR) for achieving remission with tofacitinib compared with TNFi, adjusting for potential confounders. RESULTS: This analysis included 665 patients (200 on tofacitinib and 455 on TNFi) who were followed up for at least 12 months. Of these, 96 patients in the tofacitinib group (48.0%) and 409 patients in the TNFi group (89.9%) were treatment-naïve to bDMARDs. Intention-to-treat analysis revealed no significant difference in the remission rates between the two groups (18.0% vs 19.6%, p = 0.640). Multivariable analysis demonstrated comparable remission rates with tofacitinib and TNFi (OR 1.204, 95% confidence interval [CI] 0.720-2.013). In the subpopulation naïve to JAKi and bDMARD, tofacitinib showed better remission rates than TNFi (OR 1.867, 95% CI 1.033-3.377). Tofacitinib had more adverse events (AEs) but similar rates of serious AEs (SAEs) to TNFi. CONCLUSION: In real-world settings, there was no significant difference in remission rates at 12 months between the tofacitinib and TNFi groups. In terms of safety, tofacitinib exhibited a higher incidence of AEs compared with TNFi, while the occurrence of SAEs was comparable between the groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02602704.

Examining variability in Naturalistic Developmental Behavioral Intervention strategy use in caregivers of children with autism spectrum disorders.

BACKGROUND: Naturalistic Developmental Behavioral Interventions (NDBIs) for young children with autism spectrum disorder commonly involve caregiver-mediated approaches. However, to date, there is limited research on how caregivers' skills change, and, in turn, impact child outcomes. METHODS: We evaluated the NDBI strategy use of 191 caregivers prior to participation in NDBIs (or control groups) across multiple randomized controlled trials, using the Measure of NDBI Strategy Implementation, Caregiver Change (MONSI-CC). Clustering analyses were used to examine caregiver variability in NDBI strategy use at intervention entry. Generalized Linear Mixed Models were used to examine changes in caregiver strategy use over the course of intervention and its impact on changes in children's social communication. RESULTS: Using clustering analysis, we found that caregivers' baseline skills fit four profiles: limited, emerging, variable, and consistent/high, with few demographic factors distinguishing these groups. Caregivers starting with limited or emerging skills improved in their strategy use with intervention. Caregivers starting with more skills (consistent/high or variable) maintained higher skills over intervention. Children of caregivers in these groups who received target NDBIs improved in their social communication skills. CONCLUSIONS: Results suggested that caregiver skills improve through participation in NDBIs and may directly contribute to their children's outcomes, although more research on mediating factors is needed. Individualized approaches for caregivers and their children starting with differing skill profiles at intervention entry may be warranted.

Radiosynthesis and whole-body distribution in mice of a 18 F-labeled azepino[4,3-b]indole-1-one derivative with multimodal activity for the treatment of Alzheimer's disease.

Recently, the azepino[4,3-b]indole-1-one derivative 1 showed in vitro nanomolar inhibition against butyrylcholinesterase (BChE), the ChE isoform that plays a role in the progression and pathophysiology of Alzheimer's disease (AD), and protects against N-methyl- d-aspartate-induced neuronal toxicity. Three 9-R-substituted (R = F, Br, OMe) congeners were investigated. The 9-F derivative (2a) was found more potent as BChE inhibitors (half-maximal inhibitory concentration value = 21 nM) than 2b (9-Br) and 2c (9-OMe), achieving a residence time (38 s), assessed by surface plasmon resonance, threefold higher than that of 1. To progress in featuring the in vivo pharmacological characterization of 2a, herein the 18 F-labeled congener 2a was synthesized, by applying the aromatic 18 F-fluorination method, and its whole-body distribution in healthy mice, including brain penetration, was evaluated through positron emission tomography imaging. [18 F]2a exhibited a rapid and high brain uptake (3.35 ± 0.26% ID g-1 at 0.95 ± 0.15 min after injection), followed by a rapid clearance (t1/2 = 6.50 ± 0.93 min), showing good blood-brain barrier crossing. After a transient liver accumulation of [18 F]2a, the intestinal and urinary excretion was quantified. Finally, ex vivo pharmacological experiments in mice showed that the unlabeled 2a affects the transmitters' neurochemistry, which might be favorable to reverse cognition impairment in mild-to-moderate AD-related dementias.

The Hospitalist-Oncologist co-ManagemEnt (HOME) system improves hospitalization outcomes of patients with cancer.

BACKGROUND: The hospitalist system has been introduced to improve the quality and safety of inpatient care. As its effectiveness has been confirmed in previous studies, the hospitalist system is spreading in various fields. However, few studies have investigated the feasibility and value of hospitalist-led care of patients with cancer in terms of quality and safety measures. This study aimed to evaluate the efficacy of the Hospitalist-Oncologist co-ManagemEnt (HOME) system. METHODS: Between January 1, 2019, and January 31, 2021, we analyzed 591 admissions before and 1068 admissions after the introduction of HOME system on January 1, 2020. We compared the length of stay and the types and frequencies of safety events between the conventional system and the HOME system, retrospectively. We also investigate rapid response system activation, cardiopulmonary resuscitation, unplanned intensive care unit transfer, all-cause in-hospital mortality, and 30-day re-admission or emergency department visits. RESULTS: The average length of stay (15.9 days vs. 12.9 days, P < 0.001), frequency of safety events (5.6% vs. 2.8%, P = 0.006), rapid response system activation (7.3% vs. 2.2%, P < 0.001) were significantly reduced after the HOME system introduction. However, there was no statistical difference in frequencies of cardiopulomonary resuscitation and intensive care unit transfer, all-cause in-hospital morality, 30-day unplanned re-admission or emergency department visits. CONCLUSIONS: The study suggests that the HOME system provides higher quality of care and safer environment compared to conventional oncologist-led team-based care, and the efficiency of the medical delivery system could be increased by reducing the hospitalization period without increase in 30-day unplanned re-admission.

Associations of Serum Uric Acid Level With Liver Enzymes, Nonalcoholic Fatty Liver Disease, and Liver Fibrosis in Korean Men and Women: A Cross-Sectional Study Using Nationally Representative Data.

BACKGROUND: This study aimed to determine whether serum uric acid (SUA) levels are associated with various indices of liver damage in the adult Korean population. METHODS: We used the Seventh (VII) Korean National Health and Nutritional Examination Surveys. Our study population comprised 6,007 men and 8,488 women. Levels of SUA were divided into four groups (≤ 5.3, 5.3-6.0, 6.0-7.0, and > 7.0 mg/dL for men and ≤ 4.0, 4.0-4.8, 4.8-6.0, and > 6.0 mg/dL for women). Elevated liver enzyme levels were defined as > 35 (men) and > 31 (women) IU/L for aspartate aminotransferase (AST), > 45 (men) and > 34 (women) IU/L for alanine aminotransferase (ALT). Hepatic steatosis index and fibrosis (FIB)-4 index was used to determine nonalcoholic fatty liver disease (NAFLD) and liver FIB, respectively. Adjusted odds ratios (aORs) were calculated by logistic regression analysis for liver enzymes, NAFLD, and liver FIB, according to the SUA level. RESULTS: Among women, the 4.8-6.0 and > 6.0 mg/dL SUA groups showed higher ORs of elevated AST (aOR, 1.78 and 2.03; 95% confidence interval [CI], 1.37-2.32 and 1.40-2.96, respectively; P < 0.001) and the 4.0-4.8, 4.8-6.0, and > 6.0 mg/dL SUA groups showed a higher ORs of ALT elevation (aOR, 1.35, 2.26, and 2.37; 95% CI, 1.02-1.79, 1.72-2.97, and 1.60-3.50, respectively; P < 0.001) compared to the lowest level SUA group. Among women with normal ALT, > 6.0 mg/dL SUA group showed higher OR of NAFLD status (aOR, 1.52; 95% CI, 1.06-2.19). Among men and women with NAFLD, hyperuricemia showed higher ORs of liver FIB (aOR, 2.25 and 1.89; 95% CI, 1.21-4.19 and 1.09-3.27, respectively) than the lowest level SUA group. CONCLUSION: High SUA levels may be associated with elevated liver enzymes and NAFLD, mainly in women. Even in women with normal ALT levels, SUA levels may predict the NAFLD status. Hyperuricemia may predict advanced liver FIB in both men and women with NAFLD. Further studies investigating the causal effects of SUA on liver damage are required.

Association between higher variability in kidney function and long-term mortality.

AIM: We evaluated whether estimated glomerular filtration rate variability in the general population could be associated with all-cause mortality. METHODS: Health examination data from 7842 individuals aged >20 years who visited for health check-ups at least thrice at ≥6-month intervals between May 1, 1995 and November 30, 2010 were collected. Estimated glomerular filtration rate variability was defined as the coefficient of variation of the estimated glomerular filtration rate, that is, standard deviation/mean value multiplied by 100. The study population was divided into three groups based on the coefficient of variation tertiles, and the mortality risks were compared across groups. RESULTS: The mean duration from the final visit to the outcome was 10.3 ± 2.9 years. The mean coefficient of variations of estimated glomerular filtration rate variability from the lowest to the highest variability group were 5.1 ± 1.8%, 9.0 ± 1.0%, and 14.4 ± 3.9%, respectively. There was a 1.3 times higher risk of mortality in the group with the highest variability (hazard ratio: 1.300, 95% confidence interval: 1.013-1.669) after adjustment. The findings were similar in patients with diabetes and those >60 years old (hazard ratio: 1.635, 95% confidence interval: 1.076-2.483; hazard ratio: 1.585, 95% confidence interval: 1.107-2.269). CONCLUSION: Higher estimated glomerular filtration rate variability was associated with increased 10-year mortality in the general population. This variability was very small, but considering the patients' long-term prognoses, it was significant.

A simulation-based nursing education of psychological first aid for adolescents exposed to hazardous chemical disasters.

BACKGROUND: Simulation-based education facilitates a learner-centered experience, which has been found to be effective in improving clinical performance, problem-solving ability, and self-confidence in nursing practice. The objective of this study was to develop and test a psychological first aid simulation-based education program for nurses caring for adolescents exposed to hazardous chemical disasters. METHODS: This study employed a nonequivalent pre and post-control group research design. The simulation-based education program was developed, and the participants were 30 nurses working in a medical center who were randomly assigned to the experimental, comparison, and control groups. The collected data were statistically analyzed using IBM SPSS Statistics for Windows, Ver. 22.0. RESULTS: The nurses who participated in the simulation-based education program showed statistically significantly improved psychological first aid performance knowledge, competence, and self-efficacy compared to those in the other groups. CONCLUSIONS: Nursing simulation programs could help to improve nurses' performance in mental health care and psychological support for adolescents suffering from hazardous chemical disasters.

Radiosynthesis and characterization of [18F]BS224: a next-generation TSPO PET ligand insensitive to the rs6971 polymorphism.

PURPOSE: Translocator protein 18-kDa (TSPO) positron emission tomography (PET) is a valuable tool to detect neuroinflammed areas in a broad spectrum of neurodegenerative diseases. However, the clinical application of second-generation TSPO ligands as biomarkers is limited because of the presence of human rs6971 polymorphism that affects their binding. Here, we describe the ability of a new TSPO ligand, [18F]BS224, to identify abnormal TSPO expression in neuroinflammation independent of the rs6971 polymorphism. METHODS: An in vitro competitive inhibition assay of BS224 was conducted with [3H]PK 11195 using membrane proteins isolated from 293FT cells expressing TSPO-wild type (WT) or TSPO-mutant A147T (Mut), corresponding to a high-affinity binder (HAB) and low-affinity binder (LAB), respectively. Molecular docking was performed to investigate the interaction of BS224 with the binding sites of rat TSPO-WT and TSPO-Mut. We synthesized a new 18F-labeled imidazopyridine acetamide ([18F]BS224) using boronic acid pinacol ester 6 or iodotoluene tosylate precursor 7, respectively, via aromatic 18F-fluorination. Dynamic PET scanning was performed up to 90 min after the injection of [18F]BS224 to healthy mice, and PET imaging data were obtained to estimate its absorbed doses in organs. To evaluate in vivo TSPO-specific uptake of [18F]BS224, lipopolysaccharide (LPS)-induced inflammatory and ischemic stroke rat models were used. RESULTS: BS224 exhibited a high affinity (Ki = 0.51 nM) and selectivity for TSPO. The ratio of IC50 values of BS224 for LAB to that for HAB indicated that the TSPO binding affinity of BS224 has low binding sensitivity to the rs6971 polymorphism and it was comparable to that of PK 11195, which is not sensitive to the polymorphism. Docking simulations showed that the binding mode of BS224 is not affected by the A147T mutation and consequently supported the observed in vitro selectivity of [18F]BS224 regardless of polymorphisms. With optimal radiochemical yield (39 ± 6.8%, decay-corrected) and purity (> 99%), [18F]BS224 provided a clear visible image of the inflammatory lesion with a high signal-to-background ratio in both animal models (BPND = 1.43 ± 0.17 and 1.57 ± 0.37 in the LPS-induced inflammatory and ischemic stroke rat models, respectively) without skull uptake. CONCLUSION: Our results suggest that [18F]BS224 may be a promising TSPO ligand to gauge neuroinflammatory disease-related areas in a broad range of patients irrespective of the common rs6971 polymorphism.

Risk of Tuberculosis Development in Patients with Rheumatoid Arthritis Receiving Targeted Therapy: a Prospective Single Center Cohort Study.

BACKGROUND: Patients with rheumatoid arthritis (RA) undergoing targeted therapy have a higher risk of developing tuberculosis (TB). This requires diagnosis and treatment of latent tuberculosis infection (LTBI). We aimed to evaluate whether diagnosis and treatment of LTBI in RA are effective in Korea, and to estimate the risk of TB development by calculating the incidence rate of active TB among RA patients receiving targeted therapy. METHODS: We analyzed data from two prospective cohort studies of RA patients who received biologic disease-modifying antirheumatic drugs (bDMARDs) or Janus kinase (JAK) inhibitor. We selected new starters of targeted therapy and classified them into three groups receiving tumor necrosis factor (TNF) inhibitor, non-TNF inhibitor, and JAK inhibitor, respectively. We then compared LTBI prevalence, treatments, and active TB incidence during first-line therapy in each group. RESULTS: A total of 765 RA patients (574 TNF inhibitor users, 132 non-TNF inhibitor users, and 59 JAK inhibitor users) were included in this study. Observation periods were 1,255.2 person-years (PYs), 264.7 PYs, and 53.3 PYs, respectively. All 765 patients underwent LTBI screening, and the positivity rate was 26.5% (n = 203). Of the 203 LTBI-positive patients, 189 (93.1%) received treatment. Only one patient, who was in the TNF inhibitor group, and was negative for the interferon gamma release assay (IGRA), did not receive LTBI treatment and developed active TB during follow-up. CONCLUSION: Although the prevalence of LTBI in RA patients who started targeted therapy was slightly elevated, the Korean guidelines specifying LTBI screening and treatment were effective in preventing latent TB from becoming active.

Evaluating the Relationship Between Dynamic Contrast-Enhanced MRI (DCE-MRI) Parameters and Pathological Characteristics in Breast Cancer.

BACKGROUND: Dynamic contrast-enhanced MRI (DCE-MRI) is used to evaluate tumor microvasculature. However, studies demonstrating an association between perfusion parameters derived from DCE-MRI and histopathologic characteristics are limited to a small set of histopathologic factors, and the results are inconsistent. PURPOSE: To evaluate the relationship between DCE-MRI perfusion parameters and common histopathologic tumor characteristics used to predict angiogenesis and determine prognosis in breast cancer. STUDY TYPE: Retrospective. POPULATION: In all, 105 breast cancer patients with invasive ductal carcinoma (122 lesions). FIELD STRENGTH/SEQUENCE: 3.0T, turbo spin-echo (TSE) T1 -weighted, fat-suppressed T2 -weighted, TSE T2 -weighted, and dynamic unenhanced and contrast-enhanced 3D T1 high-resolution isotropic volume examination. ASSESSMENT: One reviewer obtained perfusion parameters (Ktrans , kep , ve , and vp ) of each breast cancer from DCE MRI using the extended Tofts model with a fixed baseline T1 value and a population-based arterial input function. The relationship between DCE-MRI perfusion parameters and histopathologic tumor characteristics used to predict angiogenesis and determine prognosis was evaluated. STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, analysis of variance (ANOVA), and Kruskal-Wallis test were used. RESULTS: Triple-negative breast cancers exhibited higher Ktrans and kep than luminal cancers (P < 0.05). Estrogen receptor (ER)-negative tumors showed higher Ktrans than ER-positive tumors (P < 0.05). Progesterone receptor (PR)-negative tumors presented higher ve than PR-positive tumors (P < 0.05). Tumors with higher Ki-67 showed higher kep than tumors with lower Ki-67 (P < 0.05). P53-positive tumors exhibited higher Ktrans and kep than p53-negative tumors (P < 0.05). Higher histologic grade tumors (grade II/III) presented higher Ktrans , kep , vp (P < 0.05) than grade I tumors. Tumors with LVSI presented higher Ktrans and kep than tumors without LVSI (P < 0.05). DATA CONCLUSION: Breast cancer presenting higher Ktrans and kep on DCE-MRI was associated with poor prognostic histopathologic factors. Therefore, pretreatment DCE-MRI perfusion parameters may be useful imaging biomarkers for the evaluation of tumor prognosis and angiogenesis. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2.

Positive conversion of interferon-γ release assay in patients with rheumatic diseases treated with biologics.

The objective of this study is to investigate whether the type of biologics (TNFi or others) or type of rheumatic diseases (RA or AS) influence the conversion rate of initially negative tuberculosis (TB) screening test results. A total of 119 patients with RA or AS who had negative baseline interferon-γ release assay (IGRA) results assessed by QuantiFERON-TB Gold in tube (QTF-GIT) were included. All patients received biologic agents, and rescreening with QTF-GIT was performed after a median of 25.9 months from the baseline test. Clinical characteristics and IFN-γ levels were compared between converters and non-converters. Logistic regression analysis was performed to identify factors associated with positive conversion. IGRA conversion was found in 14 of 119 patients (11.8%). The converters were older (53.4 ± 14.2 vs 44.4 ± 15.5 years, p = 0.040), had higher baseline TB-specific IFN-γ responses (0.105 [0.018-0.205] vs 0.010 [0.000-0.035] IU/ml, p = 0.001) and higher incidence of active TB (14.3% vs 0.0%, p = 0.013). The number of patients with RA or AS was 9 (64.3%) or 5 (35.7%) in converters, and 45 (42.9%) or 60 (57.1%) in non-converters. In terms of use of biologics, TNFi of monoclonal antibody form was less commonly used in the converters (p = 0.024). In the logistic regression analysis, type of disease and type of biologics used were not associated with IGRA conversion, whereas baseline TB-specific IFN-γ response was significantly associated with IGRA conversion (OR 1.083, 95% CI 1.019-1.151, p = 0.011). Serial monitoring of LTBI with IGRA retesting is needed during biologic treatment, regardless of the type of rheumatic diseases or type biologics used.

Feasibility of the acromion index as a reference of severity of stratified supraspinatus tendon injury: a secondary analysis.

BACKGROUND: The acromion index (AI) is the acromial lateral extension above the head of the humerus. Some researchers have advocated that the AI indicates the severity of the tear size of the full-thickness supraspinatus tendon. PURPOSE: To validate the reproducibility of the AI between shoulder magnetic resonance imaging (MRI) and standard X-ray and to verify whether the AI is a useful index for stratifying the severity of supraspinatus tendon injuries, as well as full-thickness tears. MATERIAL AND METHODS: We enrolled 200 patients with impingement syndrome who were subsequently evaluated with standard X-ray of the shoulder in the anteroposterior view, as well as an MRI. We performed a pilot study to validate the reproducibility of the AI using standard X-ray and MRI, and to compare the AI between these imaging modalities. The severity of supraspinatus tendon injury was classified into four groups (0 = no evidence of injury, 1 = partial tear, 2 = full-thickness tear, and 3 = complete rupture) based on an official reading of the shoulder MRI. We compared the AIs of both modalities between the groups. RESULTS: Intraclass correlation coefficients of the AIs between the two examiners were 0.819 for MRI and 0.808 for plain X-ray. The mean AI from standard X-ray was greater than that from MRI (P<0.0001). There was no statistical correlation between the AI and the severity of supraspinatus tendon injury. CONCLUSION: Our findings indicate that the AI cannot be generally used as a predictive reference for the stratified severities of supraspinatus tendon injury.

The Prevalence of Sjögren's Syndrome in Rheumatoid Arthritis Patients and Their Clinical Features.

BACKGROUND: To estimate the prevalence of Sjögren's syndrome (SS) in patients with rheumatoid arthritis (RA) and to compare the clinical features of RA patients with and without SS. METHODS: We conducted a retrospective study of RA patients who visited a rheumatology clinic in a tertiary referral hospital in Korea between May 20 and July 22, 2016. All patients fulfilled the classification criteria for RA, and the diagnosis of SS was made clinically by rheumatologists and according to the 2002 American-European Consensus Group (AECG), 2012 American College of Rheumatology (ACR), and 2016 ACR/European League Against Rheumatism (EULAR) classification criteria. The prevalence was estimated as the number of SS patients within the total number of RA patients. The disease activity and treatment pattern of RA were compared between patients with and without SS. RESULTS: Among 827 RA patients, 72 patients (8.7%) were diagnosed with SS by a rheumatologist, though only 60 patients (7.3%) satisfied the 2002 AECG classification criteria for SS. Fifty-two patients (6.3%) and 56 patients (6.8%) fulfilled the 2012 ACR and 2016 ACR/EULAR classification criteria, respectively. The prevalence of SS in RA patients was 10.5%, 17.0%, and 67.6% in rheumatoid factor, antinuclear antibody (≥ 1:80), and anti-Ro antibody positive patients, respectively. CONCLUSION: The prevalence of SS among RA patients was 8.7% according to rheumatologists' diagnosis. The presence of SS did not affect the treatment patterns of RA patients. However, the autoantibody profiles and demographics of RA patients with SS differed from those of patients without SS.

Recent Advances in the Application of Antibacterial Complexes Using Essential Oils.

Although antibacterial spectrum of essential oils (EOs) has been analyzed along with consumers' needs on natural biocides, singular treatments generally require high concentration of EOs and long-term exposures to eliminate target bacteria. To overcome these limitations, antibacterial complex has been developed and this review analyzed previous reports regarding the combined antibacterial effects of EOs. Since unexpectable combined effects (synergism or antagonism) can be derived from the treatment of antibacterial complex, synergistic and antagonistic combinations have been identified to improve the treatment efficiency and to avoid the overestimation of bactericidal efficacy, respectively. Although antibacterial mechanism of EOs is not yet clearly revealed, mode of action regarding synergistic effects especially for the elimination of pathogens by using low quantity of EOs with short-term exposure was reported. Whereas comprehensive analysis on previous literatures for EO-based disinfectant products implies that the composition of constituents in antibacterial complexes is variable and thus analyzing the impact of constituting substances (e.g., surfactant, emulsifier) on antibacterial effects is further needed. This review provides practical information regarding advances in the EO-based combined treatment technologies and highlights the importance of following researches on the interaction of constituents in antibacterial complex to clarify the mechanisms of antibacterial synergism and/or antagonism.

Outcome and risk factors associated with perirenal subcapsular fluid collections in extremely preterm infants with acute kidney injury.

OBJECTIVES: To investigate the incidence of, clinical outcome of, and risk factors for perirenal subcapsular fluid collections in extremely preterm infants with acute kidney injury (AKI). METHODS: Extremely preterm infants with AKI who underwent renal ultrasonography (US) during neonatal intensive care unit stay were classified into two groups according to the presence of a perirenal subcapsular fluid collection at US. Clinical outcome was compared, and relevant data were analysed, including demographics and comorbidities of the infants, as well as maternal demographics. The risk factor of perirenal subcapsular fluid in infants with AKI was tested with univariate and multivariate logistic regression analysis. RESULTS: A perirenal subcapsular fluid collection was detected in 7 of 56 (13%) extremely preterm infants with AKI (male to female ratio, 5:2; mean gestational age, 23.6 ± 1.4 weeks) and it appeared bilaterally in most cases (86%, 6/7). The mortality rate was higher in infants with perirenal subcapsular fluid collections and AKI (86%, 6/7) than with AKI alone (35%, 17/49) (p = 0.015). Infants with perirenal subcapsular fluid collections and AKI were of a lower gestational age, and more frequently showed episodes of intestinal perforation, use of medication having potential to impair renal function, and a history of maternal chorioamnionitis (p < 0.05). Multivariate analysis revealed a significantly higher risk for perirenal subcapsular fluid collections in extremely preterm infants who were treated with anti-fungal agents (OR, 13.2 (95% CI: 1.5, 119.4); p = 0.022). CONCLUSIONS: Although a perirenal subcapsular fluid collection occurred in a small proportion of extremely preterm infants with AKI, its presence was associated with high mortality. The use of anti-fungal agents was an independent risk factor for a perirenal subcapsular fluid collection. KEY POINTS: • A perirenal subcapsular fluid collection may occur in association with acute kidney injury. • A perirenal subcapsular fluid collection has a grave prognostic implication in extremely preterm infants. • The use of anti-fungal agent might be associated with perirenal subscapular fluid collections in critically ill extremely preterm infants with AKI.

Prevalence of pathogenic Arcobacter species in South Korea: Comparison of two protocols for isolating the bacteria from foods and examination of nine putative virulence genes.

Contamination of foodstuffs by potentially enteropathogenic Arcobacter spp. is becoming a concern worldwide. However, few studies have examined virulence-associated genes in isolates of Arcobacter spp. from food. Here, we investigated the prevalence of three pathogenic Arcobacter species, A. butzleri, A. cryaerophilus, and A. skirrowii, in chicken, pork, and leafy green vegetables (n = 323) in South Korea. Samples were examined using two different protocols selected from a literature review: Acrobacter selective broth (ASB) II + Arcobacter selective medium (ASM) II (protocol A), and ASB II + modified charcoal cefoperazone deoxycholate agar supplemented with CAT (protocol B). Overall, Arcobacter spp. were detected in 45.8% of food samples, and the recovery rate of protocol B (37.8%) was significantly higher than that of protocol A (30.7%) (p < 0.05). Refrigerated chicken gizzard samples showed the highest detection rate (100%), followed by refrigerated chicken wing (79.5%), intestine (77.3%), neck skin (63.3%), pork (55.6%), frozen chicken legs (5.0%), and leafy green vegetables (4.4%) (p < 0.05). All isolates from chicken and leafy green vegetables were identified as A. butzleri, whereas A. cryaerophilus and A. skirrowii were mainly detected in pork. Most samples (95.8%) harbored more than one of nine putative virulence factors (cadF, ciaB, cj1349, hecA, hecB, mviN, pldA, irgA, and tlyA), and 91.3% harbored more than two. Isolates harboring all nine putative virulence genes were obtained from 1.9% of samples: five pork and one chicken. This study provides comprehensive and de facto evidence regarding prevalence of an emerging pathogen, Arcobacter spp., in various foods, along with their virulence potential. The results justify further research with respect to their role in food safety.

Comparison of Lip Line Cant Change After 1-Jaw and 2-Jaw Surgery.

OBJECTIVES: The purpose of this study was to compare the lip line cant (LLC) changes after 1 and 2-jaw surgery, and to evaluate the correlations of the craniofacial factors affecting LLC. METHODS: The study subjects were selected (LLC amount within 1.5-6.0°) from among the patients diagnosed with Class III malocclusion who underwent one (n = 20) or 2-jaw surgery (n = 20). Cone beam computed tomography images were obtained immediately before the operation (T1) and 6 months after the operation (T2). Preoperative and postoperative craniofacial measurements were obtained. RESULTS: The study subjects showed 3.12° LLC on average before undergoing 1-jaw surgery, and their LLC changed to 1.27° after the surgery. As for 2-jaw surgery, the subjects showed 3.38° LLC on average before the surgery and 0.98° after the surgery. LLC at pre-treatment may be more affected by a cant of the occlusal plane in the mandible than maxilla. In the comparison of the value of changes of LLC, the value of 2-jaw surgery was bigger than the value of 1-jaw surgery but the difference was statistically insignificant. LIMITATIONS: This study had a limitation in that the muscles were not considered. And the metal bracket or metal crown and bridge, however, can cause noise and blurring artifacts in CT, which can lead to a low resolution. And the limited number of the patients should be considered. CONCLUSIONS: In correlation analysis, both pre-surgery LLC and change of LLC have correlation with almost all the craniofacial measurement. Lip-line cant of patients with facial asymmetry has higher correlation with mandibular cant than with other cants. To improve the LLC, a surgical plan should be established to minimize the mandibular cant using the computer simulation as well as the maxillary cant.

Effects of pH and Cultivation Time on the Formation of Styrene and Volatile Compounds by Penicillium expansum.

Styrene can be formed by the microbial metabolism of bacteria and fungi. In our previous study, styrene was determined as a spoilage marker of Fuji apples decayed by Penicillium expansum, which is responsible for postharvest diseases. In the present study, P. expansum was cultivated in potato dextrose broth added with phenylalanine-which is a precursor of styrene-using different initial pH values and cultivation times. Volatile compounds were extracted and analyzed using gas chromatography-mass spectrometry (GC-MS) combined with stir-bar sorptive extraction. The 76 detected volatile compounds included 3-methylbutan-1-ol, 3-methyl butanal, oct-1-en-3-ol, geosmin, nonanal, hexanal, and γ-decalactone. In particular, the formation of 10 volatile compounds derived from phenylalanine (including styrene and 2-phenylethanol) showed different patterns according to pH and the cultivation time. Partial least square-discriminant analysis (PLS-DA) plots indicated that the volatile compounds were affected more by pH than by the cultivation time. These results indicated that an acidic pH enhances the formation of styrene and that pH could be a critical factor in the production of styrene by P. expansum. This is the first study to analyze volatile compounds produced by P. expansum according to pH and cultivation time and to determine their effects on the formation of styrene.