CRISPR activation of endogenous genes reprograms fibroblasts into cardiovascular progenitor cells for myocardial infarction therapy.

Fibroblasts can be reprogrammed into cardiovascular progenitor cells (CPCs) using transgenic approaches, although the underlying mechanism remains unclear. We determined whether activation of endogenous genes such as Gata4, Nkx2.5, and Tbx5 can rapidly establish autoregulatory loops and initiate CPC generation in adult extracardiac fibroblasts using a CRISPR activation system. The induced fibroblasts (>80%) showed phenotypic changes as indicated by an Nkx2.5 cardiac enhancer reporter. The progenitor characteristics were confirmed by colony formation and expression of cardiovascular genes. Cardiac sphere induction segregated the early and late reprogrammed cells that can generate functional cardiomyocytes and vascular cells in vitro. Therefore, they were termed CRISPR-induced CPCs (ciCPCs). Transcriptomic analysis showed that cell cycle and heart development pathways were important to accelerate CPC formation during the early reprogramming stage. The CRISPR system opened the silenced chromatin locus, thereby allowing transcriptional factors to access their own promoters and eventually forming a positive feedback loop. The regenerative potential of ciCPCs was assessed after implantation in mouse myocardial infarction models. The engrafted ciCPCs differentiated into cardiovascular cells in vivo but also significantly improved contractile function and scar formation. In conclusion, multiplex gene activation was sufficient to drive CPC reprogramming, providing a new cell source for regenerative therapeutics.

Complement C3-Deficiency-Induced Constipation in FVB/N-C3em1Hlee/Korl Knockout Mice Was Significantly Relieved by Uridine and Liriope platyphylla L. Extracts.

Complement component 3 (C3) deficiency has recently been known as a cause of constipation, without studies on the therapeutic efficacy. To evaluate the therapeutic agents against C3-deficiency-induced constipation, improvements in the constipation-related parameters and the associated molecular mechanisms were examined in FVB/N-C3em1Hlee/Korl knockout (C3 KO) mice treated with uridine (Urd) and the aqueous extract of Liriope platyphylla L. (AEtLP) with laxative activity. The stool parameters and gastrointestinal (GI) transit were increased in Urd- and AEtLP-treated C3 KO mice compared with the vehicle (Veh)-treated C3 KO mice. Urd and AEtLP treatment improved the histological structure, junctional complexes of the intestinal epithelial barrier (IEB), mucin secretion ability, and water retention capacity. Also, an improvement in the composition of neuronal cells, the regulation of excitatory function mediated via the 5-hydroxytryptamine (5-HT) receptors and muscarinic acetylcholine receptors (mAChRs), and the regulation of the inhibitory function mediated via the neuronal nitric oxide synthase (nNOS) and inducible NOS (iNOS) were detected in the enteric nervous system (ENS) of Urd- and AEtLP-treated C3 KO mice. Therefore, the results of the present study suggest that C3-deficiency-induced constipation can improve with treatment with Urd and AEtLP via the regulation of the mucin secretion ability, water retention capacity, and ENS function.

Classification of Visual Field Abnormalities in Highly Myopic Eyes without Pathologic Change.

PURPOSE: To develop a classification system of visual field (VF) abnormalities in highly myopic eyes with and without glaucoma. DESIGN: Secondary analysis of VF data from a longitudinal cohort study. PARTICIPANTS: One thousand eight hundred ninety-three VF tests from 1302 eyes (825 individuals). METHODS: All participants underwent VF testing (Humphrey 24-2 Swedish interactive threshold algorithm standard program; Carl Zeiss Meditec) and detailed ophthalmic examination. A comprehensive set of VF defect patterns was defined via observation of the 1893 VF reports, literature review, and consensus meetings. The classification system comprised 4 major types of VF patterns, including normal type, glaucoma-like defects (paracentral defect, nasal step, partial arcuate defect, arcuate defect), high myopia-related defects (enlarged blind spot, vertical step, partial peripheral rim, nonspecific defect), and combined defects (nasal step with enlarged blind spot). A subset (n = 1000) of the VFs was used to evaluate the interobserver and intraobserver agreement and weighted κ values of the classification system by 2 trained readers. The prevalence of various VF patterns and their associated factors were determined. MAIN OUTCOME MEASURES: The classification of VF in highly myopic eyes and its associated risk factors. RESULTS: We found that normal type, glaucoma-like defects, high myopia-related defects, and combined defects accounted for 74.1%, 10.8%, 15.0%, and 0.1% of all unique VF tests, respectively. The interobserver and intraobserver agreements were > 89%, and the corresponding κ values were 0.86 or more between readers. Both glaucoma-like and high myopia-related VF defects were associated with older age (odds ratios [ORs], 1.07 [95% confidence interval (CI), 1.04-1.10; P < 0.001] and 1.06 [95% CI, 1.04-1.10; P < 0.001]) and longer axial length (ORs, 1.65 [95% CI, 1.32-2.07; P < 0.001] and 1.37 [95% CI, 1.11-1.68; P = 0.003]). Longer axial length showed a stronger effect on the prevalence of glaucoma-like VF defects than on the prevalence of high myopia-related VF defects (P = 0.036). CONCLUSIONS: We propose a new and reproducible classification system of VF abnormalities for nonpathologic high myopia. Applying a comprehensive classification system will facilitate communication and comparison of findings among studies.

TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle.

RATIONALE: Trimeric intracellular cation (TRIC)-A and B are distributed to endoplasmic reticulum/sarcoplasmic reticulum intracellular Ca2+ stores. The crystal structure of TRIC has been determined, confirming the homotrimeric structure of a potassium channel. While the pore architectures of TRIC-A and TRIC-B are conserved, the carboxyl-terminal tail (CTT) domains of TRIC-A and TRIC-B are different from each other. Aside from its recognized role as a counterion channel that participates in excitation-contraction coupling of striated muscles, the physiological function of TRIC-A in heart physiology and disease has remained largely unexplored. OBJECTIVE: In cardiomyocytes, spontaneous Ca2+ waves, triggered by store overload-induced Ca2+ release mediated by the RyR2 (type 2 ryanodine receptor), develop extrasystolic contractions often associated with arrhythmic events. Here, we test the hypothesis that TRIC-A is a physiological component of RyR2-mediated Ca2+ release machinery that directly modulates store overload-induced Ca2+ release activity via CTT. METHODS AND RESULTS: We show that cardiomyocytes derived from the TRIC-A-/- (TRIC-A knockout) mice display dysregulated Ca2+ movement across sarcoplasmic reticulum. Biochemical studies demonstrate a direct interaction between CTT-A and RyR2. Modeling and docking studies reveal potential sites on RyR2 that show differential interactions with CTT-A and CTT-B. In HEK293 (human embryonic kidney) cells with stable expression of RyR2, transient expression of TRIC-A, but not TRIC-B, leads to apparent suppression of spontaneous Ca2+ oscillations. Ca2+ measurements using the cytosolic indicator Fura-2 and the endoplasmic reticulum luminal store indicator D1ER suggest that TRIC-A enhances Ca2+ leak across the endoplasmic reticulum by directly targeting RyR2 to modulate store overload-induced Ca2+ release. Moreover, synthetic CTT-A peptide facilitates RyR2 activity in lipid bilayer reconstitution system, enhances Ca2+ sparks in permeabilized TRIC-A-/- cardiomyocytes, and induces intracellular Ca2+ release after microinjection into isolated cardiomyocytes, whereas such effects were not observed with the CTT-B peptide. In response to isoproterenol stimulation, the TRIC-A-/- mice display irregular ECG and develop more fibrosis than the WT (wild type) littermates. CONCLUSIONS: In addition to the ion-conducting function, TRIC-A functions as an accessory protein of RyR2 to modulate sarcoplasmic reticulum Ca2+ handling in cardiac muscle.

Macular sector-wise decision tree model for the prediction of parafoveal scotoma not detected by 24-2 visual field test.

BACKGROUND: Development of a macular sector-wise decision tree model (DTM) for the prediction of parafoveal scotoma. METHODS: This prospective study enrolled 126 patients with early-stage open-angle glaucoma (mean deviation ≥-6 decibels) without the signs of parafoveal scotoma on the 24-2 visual field (VF) test (i.e., any abnormalities at the four innermost points). Based on the central 36 points of the 10-2 pattern deviation plot, patients were classified as being with or without 10-2 parafoveal scotoma. For the discrimination of patients from those without 10-2 parafoveal scotoma, a macular ganglion cell-inner plexiform layer (mGCIPL) sector-wise DTM analysis was performed. RESULTS: Among 126 eyes without 24-2 parafoveal scotoma, 10-2 parafoveal scotoma was detected in 77 (61.1%) eyes. The balanced accuracy of DTM was best in the inferotemporal sector (0.9286; 95% CI, 0.7458-0.9697) and worst in the inferior sector (0.8373; 0.6484-0.9204). DTM revealed that even in the absence of VF abnormalities at the innermost 4 points on the 24-2 test, (1) 10-2 parafoveal scotoma should be strongly suspected when the adjacent 24-2 perifoveal point in the correlated sector is abnormal; (2) if the 24-2 perifoveal point is normal, and if the probability colour codes of the correlated mGCIPL sector are green, the probability of 10-2 parafoveal scotoma is very low. CONCLUSIONS: In clinical practice, the evaluation of the 24-2 perifoveal test points along with the probability colour codes of mGCIPL can be a useful decision-support tool in determining whether 10-2 tests are needed for a given patient.

Explaining the Rationale of Deep Learning Glaucoma Decisions with Adversarial Examples.

PURPOSE: To illustrate what is inside the so-called black box of deep learning models (DLMs) so that clinicians can have greater confidence in the conclusions of artificial intelligence by evaluating adversarial explanation on its ability to explain the rationale of DLM decisions for glaucoma and glaucoma-related findings. Adversarial explanation generates adversarial examples (AEs), or images that have been changed to gain or lose pathologic characteristic-specific traits, to explain the DLM's rationale. DESIGN: Evaluation of explanation methods for DLMs. PARTICIPANTS: Health screening participants (n = 1653) at the Seoul National University Hospital Health Promotion Center, Seoul, Republic of Korea. METHODS: We trained DLMs for referable glaucoma (RG), increased cup-to-disc ratio (ICDR), disc rim narrowing (DRN), and retinal nerve fiber layer defect (RNFLD) using 6430 retinal fundus images. Surveys consisting of explanations using AE and gradient-weighted class activation mapping (GradCAM), a conventional heatmap-based explanation method, were generated for 400 pathologic and healthy patient eyes. For each method, board-trained glaucoma specialists rated location explainability, the ability to pinpoint decision-relevant areas in the image, and rationale explainability, the ability to inform the user on the model's reasoning for the decision based on pathologic features. Scores were compared by paired Wilcoxon signed-rank test. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivities, and specificities of DLMs; visualization of clinical pathologic changes of AEs; and survey scores for locational and rationale explainability. RESULTS: The AUCs were 0.90, 0.99, 0.95, and 0.79 and sensitivities were 0.79, 1.00, 0.82, and 0.55 at 0.90 specificity for RG, ICDR, DRN, and RNFLD DLMs, respectively. Generated AEs showed valid clinical feature changes, and survey results for location explainability were 3.94 ± 1.33 and 2.55 ± 1.24 using AEs and GradCAMs, respectively, of a possible maximum score of 5 points. The scores for rationale explainability were 3.97 ± 1.31 and 2.10 ± 1.25 for AEs and GradCAM, respectively. Adversarial example provided significantly better explainability than GradCAM. CONCLUSIONS: Adversarial explanation increased the explainability over GradCAM, a conventional heatmap-based explanation method. Adversarial explanation may help medical professionals understand more clearly the rationale of DLMs when using them for clinical decisions.

Dual respiratory virus detection in adult patients with acute respiratory illness.

BACKGROUND: Nonrandom multiple respiratory virus (RV) detection provides evidence for viral interference among respiratory viruses. However, little is known as to whether it occurs randomly. METHODS: The prevalence of dual RV detection (DRVD) in patients with acute respiratory illnesses (ARIs) at 4 academic medical centers was investigated; data about the prevalence of 8 RVs were collected from the Korean national RV surveillance dataset. Linear regression analysis was performed to assess the correlation between observed and estimated prevalence of each type of DRVD. RESULTS: In total, 108 patients with ARIs showing DRVD were included in this study between 2011 and 2017. In several types of regression analysis, a strong correlation was observed between the observed and estimated prevalence of each type of DRVD. Excluding three DRVD types (influenza/picornavirus, influenza/human metapneumovirus, and adenovirus/respiratory syncytial virus), the slope of the regression line was higher than that of the line of random occurrence (1.231 > 1.000) and the 95% confidence interval of the regression line was located above the line of random occurrence. CONCLUSIONS: Contrary to the results of previous epidemiologic studies, most types of DRVD occur more frequently than expected from the prevalence rates of individual RV, except for three underrepresented pairs above.

Visual outcomes and associated factors of primary congenital glaucoma in children.

PURPOSE: We evaluated the long-term visual outcomes in children with primary congenital glaucoma and determined the factors associated with the final visual outcomes. METHODS: Medical records of children with primary congenital glaucoma between 2005 and 2016, seen at Seoul National University Children's Hospital in South Korea, were reviewed. The minimum follow-up period after surgery for primary congenital glaucoma was 3 years. Visual acuity (VA) was categorized into good (≧20/70) and poor (< 20/70). Factors including age, VA, refractive errors, intraocular pressure (IOP), laterality, and cup-to-disc (C/D) ratio were compared between the groups. RESULTS: A total of 71 eyes of 44 patients were included. The patients' age at the time of surgery was 14.7 ± 12.2 months. The mean IOP was 28.3 ± 7.0 mmHg. During 6.7 ± 2.7 years of mean follow-up after surgery, 39 eyes (54.9%) needed occlusion treatment. After occlusion, patients with lower IOP values, lesser additional surgeries, reversal of optic disc cupping, and better initially measured VA achieved a better visual outcome. At the final assessment, the mean age was 7.8 ± 2.6 years, and the mean VA gain was 15.0 ± 19.4 letters. There were 44 eyes (62.0%) with VA ≧20/70. CONCLUSIONS: In children with primary congenital glaucoma, IOP control and the optic disc configuration over time are important factors associated with visual outcome. Regular follow-up and correction of refractive errors-along with occlusion for those with difference in VA between the two eyes-might be helpful for achieving better visual outcomes.

Critical issues concerning biocreative strategy in contemporary temporary skeletal anchorage device orthodontics: A narrative review.

Biocreative Orthodontic Strategy (BOS) is designed to establish a physiologically stable occlusion in harmony with masticatory and TMJ function and healthy supporting tissues with strategic use of temporary skeletal anchorage devices (TSADs). This narrative review surveys current research that demonstrates how BOS with TSADs uses a target approach to overcome the limitations experienced with conventional orthodontic treatment. A narrative review article including research on TSADs orthodontics in the permanent dentition. This review is a brief survey of five BOS principles for contemporary TSAD orthodontics: elegant selection of TSADs, bracket prescription to enhance TSAD orthodontics, antero-posterior dimension control, transverse dimension control and airway control issues. Severe malocclusion and craniofacial dysmorphology can be treated with Biocreative Orthodontic Strategy with a minimum number of TSADs. In order to achieve successful treatment outcome using TSADs, it is critical to understand the key diagnosis and treatment principles of BOS and how to develop a target approach for the tooth and bone movement.

Automated Real-Time Evaluation of Condylar Movement in Relation to Three-Dimensional Craniofacial and Temporomandibular Morphometry in Patients with Facial Asymmetry.

The aim of this study was to investigate the correlation between craniofacial morphology, temporomandibular joint (TMJ) characteristics, and condylar functional movement in patients with facial asymmetry using an up-to-date automated real-time jaw-tracking system. A total of 30 patients with mandibular asymmetry and prognathism were included. Three-dimensional (3D) craniofacial and TMJ morphometric variables were analyzed in images captured using cone-beam computed tomography. Three-dimensional condylar movements were recorded during the opening, protrusion, and laterotrusion of the jaw and divided into those for deviated and non-deviated sides. Overall functional and morphometric variables were compared between the sides by a paired t-test. Pearson's correlation analysis and factor analysis were also performed. As a result, significant differences were found between the sides in morphometric and functional variables. The condylar path length was significantly longer and steeper on the deviated side during protrusion and lateral excursion. TMJ morphometric asymmetry, more so than the craniofacial morphologic asymmetry, seemed to be reflected in the functional asymmetry, representing different correlations between the sides, as supported by factor analysis. This study provides evidence explaining why the asymmetric condylar path remained unchanged even after orthognathic surgery for the correction of craniofacial asymmetry.

Evaluation of interradicular space, soft tissue, and hard tissue of the posterior palatal alveolar process for orthodontic mini-implant, using cone-beam computed tomography.

INTRODUCTION: To investigate the anatomy of the posterior palatal alveolar process, which is often used for placement of the orthodontic mini-implant (OMI), and to suggest simple guidelines for safe placement of OMI. METHODS: Cone-beam computed tomography (CBCT) scans of 60 patients (30 men, 30 women; age range, 18-39 years; average age, 25.8 years) was used to measure the palatal interradicular distance, the palatal bone thickness, and the palatal soft-tissue thickness. Measurements were performed on the area from the maxillary canine to the maxillary second molar based on the vertical distance apical from the cementoenamel junction. The CBCT data were analyzed by Bonferroni correction for multiple testing and the multivariable mixed linear model. RESULTS: The palatal interradicular distance was the widest between the second premolar and the first molar and the narrowest between the first and second premolars. The palatal bone thickness at interdental sites was the thickest between the first and second premolars and the thinnest between the first and second molars. The interdental palatal soft-tissue thickness from the canine to the second premolar was thicker than any other area. There were minor measurement differences between genders and positive correlations between vertical distance from the cementoenamel junction plane and all of the parameters. CONCLUSION: In this study, we evaluated the anatomy of the posterior palatal area using CBCT scans of adult patients. The data will provide guidelines to the clinicians before OMI placement in the posterior palatal alveolar process.

Ten Years and Beyond Longitudinal Change of ß-Zone Parapapillary Atrophy: Comparison of Primary Open-Angle Glaucoma with Normal Eyes.

PURPOSE: To investigate the difference in longitudinal change of ß-zone parapapillary atrophy (PPA) between eyes with primary open-angle glaucoma (POAG) and normal eyes. DESIGN: Longitudinal, observation study. PARTICIPANTS: A total of 153 eyes with POAG and 105 normal eyes. METHODS: Participants were followed for 10 years or more, with disc photography performed every year. The topographic parameters of ß-zone PPA (area, maximal radial extent, angular extent around disc) were measured. The factors associated with the enlargement of ß-zone PPA parameters were assessed by odds ratio (OR) using multivariable logistic regression. MAIN OUTCOME MEASURES: Enlargement of ß-zone PPA parameters and associated factors. RESULTS: Over the course of the average 11.6±1.3-year follow-up period, enlargement of ß-zone PPA was detected in 66.7% of POAG eyes and in 26.7% of normal eyes. Increment of all PPA parameters was significantly more common in cases of POAG than in normal eyes (all P < 0.001). The spatial distribution of maximal radial extent at baseline and final examination was significantly different between the 2 groups: POAG eyes; inferotemporal versus normal eyes; temporal (chi-square = 26.549, P < 0.001, chi-square = 19.320, P = 0.004, respectively). The widening of radial extent was significantly associated with older age (OR, 1.036; P = 0.010) and the presence of glaucoma (OR, 2.599; P = 0.002). The increment of angular extent was associated with the presence of glaucoma (OR, 12.167; P = 0.017) and optic disc hemorrhage (OR, 3.266; P = 0.019). CONCLUSIONS: The pattern of ß-zone PPA change differed between POAG and normal eyes during a follow-up of 10 years or more. The enlargement of PPA occurred more frequently in POAG than in normal eyes. The widening of radial extent was associated with older age and glaucoma, whereas the increment of angular extent was associated with glaucomatous damage.

Twenty-four-Hour Intraocular Pressure-Related Patterns from Contact Lens Sensors in Normal-Tension Glaucoma and Healthy Eyes: The Exploring Nyctohemeral Intraocular pressure related pattern for Glaucoma Management (ENIGMA) Study.

PURPOSE: To investigate 24-hour nyctohemeral intraocular pressure (IOP)-related patterns with contact lens sensors (CLSs) in eyes with primary open-angle glaucoma (POAG) with normal baseline IOP (i.e., normal-tension glaucoma [NTG]) and healthy controls. DESIGN: Prospective, case-control study. PARTICIPANTS: Thirty eyes of 30 patients with NTG, who had had a wash-out period for their IOP-lowering treatment, and 20 eyes of 20 healthy volunteer subjects. METHODS: Patients and subjects were hospitalized for the purposes of 24-hour CLS (SENSIMED Triggerfish; Sensimed AG, Lausanne, Switzerland) measurement. The IOP-related patterns during wake and sleep times over the course of the 24 hours were compared between the 2 groups. The 24-hour ambulatory blood pressure and posture were monitored simultaneously. A generalized linear model was used to find the factors associated with NTG. MAIN OUTCOME MEASURES: The IOP-related patterns, including mean and standard deviation (SD) of measurements, amplitude of cosine-fit curve, acrophase (signal peak), and bathyphase (signal trough) values (millivolt equivalents [mVEq]). RESULTS: The SDs of the 24-hour CLS measurements were significantly greater in NTG eyes than in healthy controls (112.51±26.90 vs. 85.18±29.61 mVEq, P = 0.002). The amplitudes of cosine-fit curve (141.88±39.96 vs. 106.08±41.49 mVEq, P = 0.004) and acrophase values (277.74±129.80 vs. 190.58±127.88 mVEq, P = 0.024), mostly measured during nocturnal period, were significantly greater in NTG eyes than in healthy controls. The NTG subjects slept longer in the lateral decubitus posture than the healthy controls (199.1±137.8 vs. 113.2±86.2 minutes, P = 0.009). In the multivariable generalized linear model, the greater amplitude of cosine-fit curve (ß = 0.218, P = 0.012) and greater time of decubitus posture during sleep (ß = 0.180, P = 0.004) were found to be significantly associated with NTG. CONCLUSIONS: Continuous monitoring of 24-hour IOP-related values with CLS can be useful for assessment of glaucoma risk, especially for patients with NTG whose IOP appears to be in the normal range. Fluctuation of 24-hour IOP-related values and posture during sleep time might be associated with NTG.

Management and outcomes of Burkholderia cepacia complex bacteremia in patients without cystic fibrosis: a retrospective observational study.

Burkholderia cepacia complex (BCC) is an emerging pathogen of nosocomial infection in chronic or critically ill patients without cystic fibrosis (CF). The objective was to evaluate the management and outcomes of BCC bacteremia in patients without CF. We conducted a retrospective study of non-CF adult patients with BCC bacteremia between January 1997 and December 2016 at 4 tertiary hospitals in South Korea. A total of 216 non-CF patients with BCC bacteremia were identified. Most cases were hospital-acquired (79.2%), and the most common source was a central venous catheter (CVC) (42.1%). The rates of susceptibility to trimethoprim-sulfamethoxazole and piperacillin-tazobactam of BCC isolates were high as 92.8% and 90.3%, respectively. The rates of susceptibility to ceftazidime, meropenem, and levofloxacin were 75.5%, 72.3%, and 64.1%, respectively. The 14-day, 30-day, and in-hospital mortality rate was 19.4%, 23.1%, and 31.0%, respectively. Female (OR = 3.1; 95% CI, 1.4-6.8), liver cirrhosis (OR = 6.2; 95% CI, 1.6-16.6), septic shock (OR = 11.2; 95% CI, 5.1-24.8), and catheter-related infection (OR = 2.6, 95% CI, 1.2-5.8) were the independent risk factors for 30-day mortality. The outcome did not differ according to type of antibiotics used. Among 91 patients with CVC-related BCC bacteremia, delayed CVC removal (> 3 days) had a higher rate of persistent bacteremia (54.5 vs. 26.1%; P = 0.03) and lower rate of clinical response (49.0 vs. 71.9%; P = 0.04), compared with early CVC removal (within 3 days). BCC bacteremia occurring in non-CF patients was mostly hospital-acquired and CVC-related. Early removal of the catheter is crucial in treatment of CVC-related BCC bacteremia.

Long-term methicillin-resistant Staphylococcus aureus bacteremia persisting for more than 2 weeks: risk factors and outcomes.

The clinical significance of long-term methicillin-resistant Staphylococcus aureus (MRSA) bacteremia remains unclear. We evaluated the clinical, microbiological characteristics, and clinical outcomes of long-term MRSA bacteremia. A nested case-control study was conducted in a prospective cohort of adult patients with MRSA bacteremia at a tertiary hospital between August 2008 and December 2017. Patients with long-term MRSA bacteremia (≥ 14 days) were compared with control patients, defined as having bacteremia that resolved in less than 3 days. The following variables were documented: heteroresistance phenotype, genotypes, agr dysfunction, and the presence of 41 virulence genes in isolates. Of the total 890 patients studied, 69 patients (7.8%) exhibited long-term MRSA bacteremia and 599 (67.3%) exhibited resolving bacteremia. The most common sources of long-term bacteremia were central venous catheter-related infection (39%) and osteomyelitis (19%). Independent risk factors for long-term MRSA bacteremia included male sex (adjusted odds ratio [aOR] = 2.43), community-acquired bacteremia (aOR = 2.93), the presence of a prosthetic device (aOR = 3.40), and osteomyelitis (aOR = 7.98). Metastatic infections developed more frequently in patients with long-term bacteremia than in those with resolving bacteremia (56.5% vs. 8.0%; P < 0.001). Although there were no significant differences in 30-day, 12-week, or in-hospital mortality rates between the two groups, infection-attributable mortality was higher in the long-term bacteremia group (23.2% vs. 11.5%; P = 0.01). Microbiological characteristics did not differ significantly between the two groups. Clinical factors, including community-acquired bacteremia, the presence of a prosthetic device, and osteomyelitis, appear to contribute to long-term MRSA bacteremia more than microbiological factors.

Persistent Acinetobacter bereziniae Bacteremia in a Pregnant Woman.

BACKGROUND: Persistent Acinetobacter bereziniae bacteremia in a pregnant woman has not previously been reported. METHODS: A 25-year-old pregnant Kyrgyz woman developed a fever after McDonald operation. Serial blood cultures were performed. RESULTS: Multidrug-resistant Acinetobacter was isolated. She was prescribed meropenem. A. bereziniae was successfully identified by MALDI-TOF MS with an updated library, and 16S rRNA gene sequencing analysis supported the result. CONCLUSIONS: The multidrug-resistant features of A. bereziniae and the therapeutic concentration of antibiotic agents during pregnancy had to be considered in the present case.

Surface Roughness on the Slots and Wings of Various Ceramic Self-Ligating Brackets and their Potential Concern on Biofilm Formation.

OBJECTIVE: The surface roughness of various orthodontic materials could affect biofilm formation and friction. The purpose of this study was to examine the surface roughness and chemical composition of the slots and wings of several ceramic self-ligating brackets. STUDY DESIGN: Four types of ceramic self-ligating brackets were separated into experimental groups (DC, EC, IC, and QK) while a metal self-ligating bracket (EM) was used as the control group. Atomic force microscopy and energy-dispersive x-ray spectroscope were used to examine the surface roughness and chemical composition of each bracket slot and wing. RESULTS: The control group was made of ferrum and chrome while all the experimental groups were comprised of aluminum and oxide. There was a statistically significant difference in the roughness average (Sa) among the various self-ligating brackets (p< 0.001 in slots and p<0.01 in the wing). The slots in the EC group had the lowest Sa, followed by the DC, IC, control, and QK groups. The wings in the IC group had the lowest Sa, followed by the EC, DC, control, and QK groups. CONCLUSIONS: There is a significant difference in the surface roughness of the slots and wings among several types of ceramic self-ligating brackets.

Clinical and Molecular Characteristics of qacA- and qacB-Positive Methicillin-Resistant Staphylococcus aureus Causing Bloodstream Infections.

The increasing use of chlorhexidine for methicillin-resistant Staphylococcus aureus (MRSA) decolonization has raised concerns about the emergence of resistance to these agents. However, the clinical significance of MRSA positive for the qacA and qacB chlorhexidine tolerance genes has not been established. We investigated the clinical features and predictive factors of MRSA bloodstream infection (BSI) isolates, caused by qacA- and qacB-positive MRSA, from 2010 to 2016 at a tertiary hospital in South Korea. A total of 246 MRSA BSI isolates were included; 71 (28.9%) isolates carried qacA/B The annual frequency of qacA- and qacB-positive MRSA bacteremia did not change significantly over the study period. Patients infected with qacA- and qacB-positive MRSA had common risk factors for health care-associated infections, including prior antibiotic use, central venous catheterization in situ, intensive care unit-acquired bacteremia, and nosocomial infection. The qacA- and qacB-positive isolates were also associated with an increasing chlorhexidine MIC and resistance to non-ß-lactam antibiotics. The qacA- and qacB-positive isolates were more likely to belong to sequence type 5 (ST5), which is a common health care-associated MRSA strain in South Korea. In multivariable analyses, qacA- and qacB-positive MRSA isolates were found to be associated with agr dysfunction (adjusted odds ratio [aOR], 6.45; 95% confidence interval [CI], 2.59 to 16.10), ST5 MRSA strain (aOR, 4.96; 95% CI, 1.85 to 13.26), nosocomial infection (aOR, 4.88; 95% CI, 2.20 to 10.83), and antibiotic use within the previous 3 months (aOR, 2.59; 95% CI, 1.20 to 5.59). These findings suggest that the microbiological features of qacA and qacB carriage provide a selective advantage for specific MRSA strains in hospital environments.

Temporal Raphe Sign for Discrimination of Glaucoma from Optic Neuropathy in Eyes with Macular Ganglion Cell-Inner Plexiform Layer Thinning.

PURPOSE: To evaluate the potential of the temporal raphe sign on the macular ganglion cell-inner plexiform layer (mGCIPL) thickness map for discriminating glaucomatous from nonglaucomatous optic neuropathy (NGON) in eyes with mGCIPL thinning. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 175 eyes of 175 patients with mGCIPL thinning on Cirrus (Carl Zeiss Meditec, Dublin, CA) high-definition OCT were retrospectively included. Glaucoma specialists and neuro-ophthalmology specialists evaluated the patients' medical records for diagnosis of glaucomatous optic neuropathy (GON) or NGON. Finally, by consensus, 67 eyes with GON and 73 eyes with NGON were enrolled. METHODS: A positive temporal raphe sign was declared in patients in whom there was a straight line longer than one-half of the length between the inner and outer annulus in the temporal elliptical area of the mGCIPL thickness map. Decision tree analysis was performed to formulate a diagnostic model. MAIN OUTCOME MEASURES: Area under receiver operating characteristic curve (AUC) with sensitivity and specificity. RESULTS: The temporal raphe sign was observed in 61 of 67 GON eyes (91.0%), but in only 21 of 73 NGON eyes (28.8%) (P < 0.001; chi-square test). On this basis, the diagnostic ability of the temporal raphe sign for discriminating GON from NGON was judged to be good (AUC, 0.811; 95% confidence interval, 0.749-0.874; sensitivity, 91.0%; specificity, 71.2%). The diagnostic performance of the decision tree-based model (AUC 0.879; 95% confidence interval, 0.824-0.933; sensitivity, 88.1%; specificity, 87.7%) was better than that of the temporal raphe sign or the relative afferent pupillary defect (RAPD) alone (P = 0.005, P < 0.001, respectively; DeLong's test). The decision tree model revealed the following: (1) If the temporal raphe sign is positive and the RAPD is absent, the case should be diagnosed as GON; (2) if the temporal raphe sign is absent regardless of the presence or absence of the RAPD, or both the temporal raphe sign and the RAPD are present, the case should be diagnosed as NGON. CONCLUSIONS: In clinical practice, determining whether the temporal raphe sign appears on OCT macular scans can be a useful tool for discrimination of glaucomatous from nonglaucomatous mGCIPL thinning.

Impact of health care-associated community-onset cellulitis in Korea: a multicenter study.

We conducted a multicenter study to determine the clinical and microbiological characteristics of health care-associated (HCA) cellulitis in Korea. We retrospectively reviewed the medical records of patients who had been diagnosed with community-onset cellulitis. Of the 2208 cellulitis patients, 232 (10.5%) had HCA cellulitis, 1243 (56.3%) patients were hospitalized, and 15 (0.7%) died in hospital. Compared with community-acquired (CA) cellulitis, patients with HCA cellulitis were older and more frequently presented with comorbidity and septic shock. A total of 355 microorganisms were isolated from 314 patients (14.2%). Staphylococcus aureus (134 isolates) was the most common organism, followed by Streptococcus spp. (86 isolates) and Gram-negative fermenters (58 isolates). Methicillin-resistant S. aureus (MRSA) accounted for 29.1% (39/134) of S. aureus infections. None of the Gram-negative fermenters were resistant to carbapenem. The antibiotic susceptibility pattern of isolated microorganisms was not different between HCA and CA cellulitis. In patients with HCA cellulitis, S. aureus (11.2% [26/232] vs. 5.5% [108/1976], p = 0.001), including MRSA (4.3% [10/232] vs. 1.5% [29/1976], p = 0.003) and Gram-negative fermenters (6.0% [14/232] vs. 2.3% [44/1976], p = 0.002), were more common causative organisms than in CA-cellulitis patients. Age ≥ 65 years, septic shock, and HCA infection were statistically significant factors associated with in-hospital mortality.