Background: The purpose of this study was to find out the relationship between appropriateness of antibiotic prescription and clinical outcomes in patients with community-acquired acute pyelonephritis (CA-APN). Methods: A multicenter prospective cohort study was performed in 8 Korean hospitals from September 2017 to August 2018. All hospitalized patients aged ≥19 years diagnosed with CA-APN at admission were recruited. Pregnant women and patients with insufficient data were excluded. In addition, patients with prolonged hospitalization due to medical problems that were not associated with APN treatment were excluded. The appropriateness of empirical and definitive antibiotics was divided into “optimal,” “suboptimal,” and “inappropriate,” and optimal and suboptimal were regarded as appropriate antibiotic use. The standard for the classification of empirical antibiotics was defined reflecting the Korean national guideline for the antibiotic use in urinary tract infection 2018. The standards for the classification of definitive antibiotics were defined according to the result of in vitro susceptibility tests of causative organisms. Clinical outcomes including clinical failure (mortality or recurrence) rate, hospitalization days, and medical costs were compared between patients who were prescribed antibiotics appropriately and those who were prescribed them inappropriately. Results: In total, 397 and 318 patients were eligible for the analysis of the appropriateness of empirical and definitive antibiotics, respectively. Of these, 10 (2.5%) and 18 (5.7%) were inappropriately prescribed empirical and definitive antibiotics, respectively, and 28 (8.8%) were prescribed either empirical or definitive antibiotics inappropriately. Patients who were prescribed empirical antibiotics appropriately showed a lower mortality rate (0 vs 10%; P = .025), shorter hospitalization days (9 vs 12.5 days; P = .014), and lower medical costs (US$2,333 vs US$4,531; P = .007) compared to those who were prescribed empirical antibiotics “inappropriately.” In comparison, we detected no significant differences in clinical outcomes between patients who were prescribed definitive antibiotics appropriately and those who were prescribed definitive antibiotics inappropriately. Patients who were prescribed both empirical and definitive antibiotics appropriately showed a lower clinical failure rate (0.3 vs 7.1%; P = .021) and shorter hospitalization days (9 vs 10.5 days; P = .041) compared to those who were prescribed either empirical or definitive antibiotics inappropriately. Conclusions: Appropriate use of antibiotics leads patients with CA-APN to better clinical outcomes including fewer hospitalization days and lower medical costs.

Funding: No

Disclosures: None

Table 1.

Table 2.

The explosive outbreak of COVID-19 led to a shortage of medical resources, including isolation rooms in hospitals, healthcare workers (HCWs) and personal protective equipment. Here, we constructed a new model, non-contact community treatment centres to monitor and quarantine asymptomatic and mildly symptomatic COVID-19 patients who recorded their own vital signs using a smartphone application. This new model in Korea is useful to overcome shortages of medical resources and to minimise the risk of infection transmission to HCWs.

Mycoplasma pneumoniae is a main pathogen causing community-acquired pneumonia in children and young adults. Since the emergence of macrolide-resistant M. pneumoniae in the early 2000s in Japan, it has been increasingly reported worldwide as a growing problem in treatment for children. With increasing macrolide-resistant M. pneumoniae and limited data regarding its characterization and molecular analysis, we investigated the dominant M. pneumoniae strains during the recent outbreak in South Korea, and evaluated if there was an association between a specific type and macrolide resistance. Between October 2014 and December 2016 in South Korea, 249 respiratory specimens obtained from patients with confirmed M. pneumoniae pneumonia were genotyped the P1 adhesin gene, and the mutations associated with resistance (A2063G and A2064G) were tested by sequencing the targeted domain V regions of the 23S ribosomal RNA gene. Results revealed that M. pneumoniae type 1 were predominant, which was strongly associated with macrolide-resistance during the whole study period. This is the first study assessing whether M. pneumoniae subtype is related to macrolide resistance during the outbreak of M. pneumoniae.

OBJECTIVES/SPECIFIC AIMS: One of the driving mechanisms of cancer progression is the reprogramming of metabolic pathways in intermediary metabolism. Cancers increase their energy expenditure by increasing ATP production for utilization in anabolic pathways to increase production of proteins, nucleic acids and lipids. The Warburg effect, where cancer cells predominantly use aerobic glycolysis rather than oxidative phosphorylation to produce ATP, was long thought to be the main initiating pathway in increasing tumor burden. However, compelling new evidence shows that there exists metabolic heterogeneity among and within tumors. Mitochondrial respiration often plays a major role in tumor progression, as many different cancers contain a subpopulation of slow-cycling tumor-initiating cells that are multidrug-resistant and dependent on oxidative phosphorylation. These cells represent a target for cancer therapy. In this study, we identification a novel endogenous regulator of mitochondrial respiration, retinoic acid receptor responder 1 (RARRES1). METHODS/STUDY POPULATION: We assessed the metabolic phenotype of RARRES1-depleted normal epithelial cells through metabolomics, a flux analyzer and blotting for phosphorylation of AMP kinase, a major regulator of energy homeostasis. We further examined mitochondrial energetics by staining the mitochondria with TMRM and Mito-Tracker. We then analyzed the apoptotic phenotype of epithelial cells with depletion of RARRES1 with fluorescence-activated cell sorting analysis of annexin V-staining. RESULTS/ANTICIPATED RESULTS: Remarkably, fluorescence-activated cell sorting analysis of annexin V-stained epithelial cells with depletion of RARRES1 were resistant to all studied modes of cell death, implying an effect on a fundamental cell process. By using proteomics, metabolomics, cellular and molecular analyses, our data show that RARRES1 regulates mitochondrial membrane potential and subsequently alters 1-carbon metabolism by modulating the function of the mitochondrial voltage-dependent anion channel. We believe this is the first example of a tumor suppressor protein that functions to directly regulate mitochondrial energetics. Using an extracellular flux analyzer, our data also show that depletion of RARRES1 causes an increase in mitochondrial respiration and ATP production, thus enhancing biosynthetic pathways that drive the pathogenicity and survival of cancer. The metabolic and anti-apoptotic phenotype of RARRES1-depleted cells was reversed by treatment of metformin, a mitochondrial inhibitor. DISCUSSION/SIGNIFICANCE OF IMPACT: These data lay the foundation for metabo-therapy of the many tumor types that exhibit RARRES1 depletion and may have the added benefit of targeting drug-resistant tumor-initiating cells.

Little is known about longitudinal changes of the first twin presentation in twin gestations. This is a retrospective cohort study including 411 women who were admitted consecutively and delivered live-born twins at 36 weeks of gestation or more. Longitudinal assessment of the first twin presentation was conducted during gestation and at birth in all cases. Gestational age at antenatal assessment was divided into two intervals: early-third trimester (28–31 weeks) and mid-third trimester (32–35 weeks). Fetal presentation was categorized as vertex or non-vertex. We analyzed change of fetal presentation between antepartum intervals and birth. First twin presentation at early-third trimester had the same presentation at birth in 87.6% (360/411) of the study population. In this ‘no change’ group, vertex presentation was seen in 95.6% (283/296) and non-vertex was seen in 67.0% (77/115) of cases. In total, 96.1% (395/411) of the study population maintained their presentation between mid-third trimester and birth. Vertex presentation was seen in 98.4% (310/315) and non-vertex was seen in 88.5% (85/96) of cases. When comparing vertex with non-vertex, vertex presentation during third trimester was a more reliable predictor of presentation at birth (p < .001). The only factor that contributed significantly to spontaneous version of the first twin during mid-third trimester and birth was a lower birth weight of the first twin compared with the second twin. In conclusion, first twin presentation with vertex during third trimester is not likely to change into non-vertex at birth. We concluded that vertex presentation in twin gestations at early- and mid-third trimester is very predictable. In contrast, a non-vertex first twin presentation is relatively unstable.

OBJECTIVES/SPECIFIC AIMS: The goal of this study is to examine bioenergetic phenotype of retinoic acid receptor responder 1 (RARRES1)-depleted epithelial cells and to facilitate the discovery of personalized metabo-therapeutics in the context of cancers characterized with loss of or low expression of RARRES1. METHODS/STUDY POPULATION: Anoikis assay and annexinV labeling were used to assess drug resistance and apoptotic phenotype in RARRES1-depleted epithelial cells. Metabolomics, AMP kinase activity, mito-tracker, and extracellular flux assays were used to examine the bioenergetic profile of RARRES1-depleted epithelial cells. Extracellular flux assays were used to assess the phenotype of RARRES1-depleted epithelial cells treated with or without metformin. RESULTS/ANTICIPATED RESULTS: RARRES1 is a major regulator of mitochondrial function. Its depletion in tumors induces an oxidative phosphorylation dependent phenotype and subsequently increases ATP abundance in the cell, enhances anabolic pathways and increases survival. Treatment with FDA approved mitochondrial respiration inhibitor, metformin, reversed the metabolic phenotype of RARRES1 depleted-epithelial cells. Metformin could be the ideal therapeutics to reduce tumor burden in cancers with loss of or low expression of RARRES1. DISCUSSION/SIGNIFICANCE OF IMPACT: Bioenergetic dynamics are emerging as a basis for understanding the pathology of cancer. The malignancy progresses as its metabolic pattern and mitochondrial respiration become more dysfunctional. The regulatory pathways of bioenergetic dynamics are currently poorly understood, and the characterization of proteins implicated in those processes must be assessed. One understudied protein and tumor suppressor is RARRES1. RARRES1 is induced by retinoic acid (a major metabolic regulator) and functions as a putative carboxypeptidase inhibitor. Understanding the connection between this carboxypeptidase inhibitor and intermediary metabolism will enlighten our understanding of the bioenergetic profile of cells and facilitate the discovery of personalized metabo-therapeutics in the context of cancer.

During the past decade, carbapenemase-producing Enterobacteriaceae (CPE) has emerged and spread across the world.1 The major carbapenemase enzymes currently being reported are KPC, NDM-1, VIM, IMP, and OXA.2 Because carbapenemase can be effectively transmitted via mobile genetic elements, and current therapeutic options for CPE infections are extremely limited, CPE may be one of the most serious contemporary threats to public health. However, very little is known about the characteristics of CPE carriage during hospitalization. The aims of this study were to investigate the clearance rate of CPE carriage and determine the number of consecutive negative cultures required to confirm CPE clearance. We also examined CPE transmission among hospitalized patients.

Infect. Control Hosp. Epidemiol. 2015;36(11):1361–1362

Genetic factors have been suggested to be one of the determinants of the variation of left ventricular (LV) structure and function. However, the heritability range of LV structure varies across studies and the influence of genetics on LV function is not well established, especially in Asian populations. Study subjects were 1,642 healthy Korean adults from 426 families, consisting of 298 pairs of monozygotic twins, 62 pairs of dizygotic twins, one set of triplets, 567 siblings, and 354 parents. LV structure and function were measured by M-mode and 2D echocardiography, and conventional and tissue Doppler imaging (TDI). Pairwise intra-class correlations for various familial relationships and heritability were estimated for LV structure and function. The heritability of LV mass, LV ejection fraction (LVEF), left atrial volume index, the ratio between early and late diastolic velocity of mitral inflow (E/A ratio), and the ratio between early diastolic velocity of mitral inflow and early diastolic mitral annular velocities (E/Ea ratio) was 0.44, 0.27, 0.44, 0.25, and 0.33, respectively. Bivariate genetic analysis showed that LV structural and functional traits had significant genetic correlations with cardiovascular risk factors. Additive genetic correlation (ρG) of LV mass with body mass index, systolic blood pressure, and high density lipoprotein cholesterol were 0.49, 0.42, and -0.15 respectively. LVEF (ρG = 0.33) and left atrial volume index (ρG = 0.24) also had a significant genetic correlation with systolic blood pressure. These findings support the theory that genetic factors have significant influence on these traits and necessitate further work to identify the specific genes involved.

Recent studies suggest that ketamine produces antidepressant actions via stimulation of mammalian target of rapamycin (mTOR), leading to increased levels of synaptic proteins in the prefrontal cortex. Thus, mTOR activation may be related to antidepressant action. However, the mTOR signalling underlying antidepressant drug action has not been well investigated. The aim of the present study was to determine whether alterations in mTOR signalling were observed following treatment with antidepressant drugs, using ketamine as a positive control. Using Western blotting, we measured changes in the mTOR-mediated proteins and synaptic proteins in rat hippocampal cultures. Dendritic outgrowth was determined by neurite assay. Our findings demonstrated that escitalopram, paroxetine and tranylcypromine significantly increased levels of phospho-mTOR and its down-stream regulators (phospho-4E-BP-1 and phospho-p70S6K); fluoxetine, sertraline and imipramine had no effect. All drugs tested increased up-stream regulators (phospho-Akt and phospho-ERK) levels. Increased phospho-mTOR induced by escitalopram, paroxetine or tranylcypromine was significantly blocked in the presence of specific PI3K, MEK or mTOR inhibitors, respectively. All drugs tested also increased hippocampal dendritic outgrowth and synaptic proteins levels. The mTOR inhibitor, rapamycin, significantly blocked these effects on escitalopram, paroxetine and tranylcypromine whereas fluoxetine, sertraline and imipramine effects were not affected. The effects of escitalopram, paroxetine and tranylcypromine paralleled those of ketamine. This study presents novel in vitro evidence indicating that some antidepressant drugs promote dendritic outgrowth and increase synaptic protein levels through mTOR signalling; however, other antidepressant drugs seem to act via a different pathway. mTOR signalling may be a promising target for the development of new antidepressant drugs.

Cataract, defined as opacity of the lens in one or both eyes, is a major cause of blindness throughout the world, and not uncommon, particularly in the elderly population. However, congenital cataracts are rare and occur with a frequency of 30 cases in 100,000 births. About one-third of the cases fall into the group inherited without systemic abnormality. Importantly, congenital cataracts produce deprivation amblyopia, refractive amblyopia, and retinal detachment, leading to lifelong visual impairment. Successful management is dependent on early diagnosis and referral for surgery when indicated. Here we present a case of hereditary bilateral cataracts in a dizygotic twin detected on prenatal ultrasound examinations and postnatally confirmed as congenital cataracts associated with posterior lenticonus.

We investigated microstructures, compositional distributions, and electrical properties of dielectric CaCu3Ti4O12 (CCTO) thin films deposited on Pt/TiO2/SiO2/Si substrates from 700 to 800 °C by pulsed laser deposition. With increasing the deposition temperature from 700 to 750 °C, the dielectric constants (εr) of CCTO films were greatly enhanced from ∼300 to ∼2000 at 10 kHz, respectively. However, the εr values of CCTO films were gradually decreased above 750 °C, which was surely attributable to the formation of a TiO2-rich dead layer at the interface between CCTO and Pt electrode. Compositional analyses by Auger electron spectroscopy, energy dispersive spectroscopy, and electron energy loss spectroscopy revealed that the TiO2-rich dead layer became thicker because of severe Cu diffusion from CCTO films to Pt electrode. The leakage current behaviors of CCTO films are in good agreement with Poole–Frenkel conduction mechanism, where both the TiO2-rich dead layer and rutile TiO2 nanocrystalline particles are considered to play a role of charge trapping centers.

The effects of tannic acid (TA) supplementation (0·02 %, wt/wt) were compared with the effects of clofibrate (CF) supplementation (0·02 %, wt/wt) in apo E-deficient (apo E− / −) mice fed a AIN-76 semi-synthetic diet (normal diet) over 20 weeks. The mice were monitored for the modulation of hepatic mRNA expression and the activities of lipid-regulating enzymes. Both TA and CF supplementation lowered hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) activity and prevented atherosclerotic lesion formation in comparison with the control group. Hepatic carnitine palmitoyl transferase and β-oxidation activities were significantly higher in the TA and CF groups than in the control group. Both CF and TA supplementation resulted in significant decreases in hepatic HMGR mRNA levels in association with its enzyme activity. However, in contrast to CF supplementation, TA supplementation seemed to decrease the accumulation of hepatic lipids in the apo E− / − mice without increasing liver weight. These results suggest that the overall effect of TA is more desirable than CF for the alleviation of hepatic lipogenesis and atherogenesis in apo E− / − mice.