Remodeling of sorafenib as an orally bioavailable ferroptosis inducer for Lung Cancer by chemical modification of adenine-binding motif.

Sorafenib (BAY 43-9006) was developed as a multi-kinase inhibitor to treat advanced renal cell, hepatocellular, and thyroid cancers. The cytotoxic effect of sorafenib on cancer cells results from not only inhibiting the MEK/ERK signaling pathway (the on-target effect) but also inducing oxidative damage (the off-target effect). The inhibitory effect of sorafenib on system Xc- (xCT), a cystine/glutamate antiporter, promotes ferroptosis induction and accounts for oxidative damage. While emerging studies on ferroptosis in cancers have garnered increasing attention, the lack of consideration for ferroptosis inducers (FINs) with favorable pharmacokinetics could be problematic. Herein, we remodeled the chemical structure of sorafenib, of which pharmacokinetics and safety are already assured, to customize the off-target effect (i.e., ferroptosis induction) to on-target by disrupting the adenine-binding motif. JB3, a sorafenib derivative (i.e., JB compounds), with a tenfold higher IC50 toward RAF1 because of chemical remodeling, induced strong cytotoxicity in the elastin-sensitive lung cancer cells, while it was markedly reduced by ferrostatin-1. The 24% oral bioavailability of JB3 in rats accounted for a significant anti-tumor effect of orally administrated JB3 in xenograft models. These results indicate that JB3 could be further developed as an orally bioavailable FIN in novel anti-cancer therapeutics.

Salmonellosis outbreaks linked to eggs at 2 gimbap restaurants in Korea.

OBJECTIVES: Salmonellosis outbreaks occurred at 2 restaurants 2 days apart, and an epidemiological investigation was conducted to determine whether the outbreaks were connected. METHODS: Case studies were conducted for both outbreaks. Stool samples were collected from individuals, and food samples were collected from the restaurants. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing analyses were performed on outbreak-related Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) isolates. Traceback investigations were also conducted for the ingredients from gimbap restaurants A and B. RESULTS: In total, 106 people from gimbap restaurant A and 5 from gimbap restaurant B met the case definition. Salmonella Enteritidis was detected in samples from 2 food handlers, 22 patients, and 1 food (iceberg lettuce) at gimbap restaurant A and from 1 patient at gimbap restaurant B. According to PFGE, all isolates were identified as SEGX01.089. The molecular typing of all isolates showed the same pattern, and the genetic distance was close according to phylogenetic analysis. Eggs were the only food ingredient that was supplied to both gimbap restaurants. CONCLUSIONS: The outbreaks were caused by Salmonella Enteritidis, and the source of infections was suspected to be contaminated eggs. To prevent foodborne outbreaks of Salmonella, restaurants should heat eggs sufficiently, and egg farms need to establish management systems that prevent Salmonella infections.

Epidemiological analysis and prevention strategies in response to a shigellosis cluster outbreak: a retrospective case series in an alternative school in the Republic of Korea, 2023.

BACKGROUND: In March 2023, an alternative school in the Republic of Korea reported 12 cases of shigellosis. This study aims to analyze the epidemiological characteristics in order to determine the cause of the cluster outbreak of shigellosis and to develop prevention strategies. METHODS: This study focused on 12 patients with confirmed Shigella infection and investigated their demographics, clinical features, epidemiology, diagnostics, and antimicrobial susceptibility. Following the identification of Shigella, we conducted follow-up rectal smear cultures to manage patients, implementing isolation and control measures. RESULTS: This study investigated the emergence of multidrug-resistant Shigella following missionary activities in Cambodia, documenting a cluster infection within an alternative school in Daejeon, the Republic of Korea. The outbreak affected 56 participants, resulting in the confirmation of 12 cases. The incidence rates varied by gender and occupation, with higher rates among males and teachers. All 12 cases demonstrated multidrug resistance. Challenges included delayed pathogen confirmation and suboptimal adherence to isolation criteria. The incident prompted revisions in the criteria for isolation release, focusing on symptom resolution. The study underscores the necessity for strengthened surveillance, educational initiatives focusing on prevention in endemic areas, and improved oversight of unlicensed educational establishments. CONCLUSION: Successful response strategies included swift situation assessment, collaborative efforts, effective infection control measures, and modified criteria for isolation release. Continued surveillance of multidrug-resistant strains is recommended, especially in regions with a high prevalence.

Parenting practices, mental health, and electronic cigarette use among U.S. young adolescents: A longitudinal panel analysis, 2013-2018.

PURPOSE: This study examined prospective association of parenting practices related to tobacco use with adolescent e-cigarette use and the moderating role of mental health among U.S. young adolescents. METHODS: We study used multi-wave longitudinal data (2013-2018) drawn from the Population Assessment of Tobacco and Health Study. A total of 5114 young adolescents (12-14 years) who were not lost to follow-ups across four waves (Wave 1-4) comprised the study sample. Weighted logistic regression models along with generalized linear mixed modeling assessed the within-subject associations of parenting practices related to tobacco use (tobacco availability at parent/guardian's home, past-year parent talk about tobacco use, and rules about non-combustible tobacco use at home) with adolescent current e-cigarette use. RESULTS: Prevalence of having home rules about non-combustible tobacco use increased (74.5%-80.2%) and that of parent talk about tobacco use decreased (52.0%-33.9%) over time while tobacco availability at home did not show a specific trend. Tobacco availability at home was associated with increased odds of adolescent e-cigarette use (adjusted odd ratio[OR] = 2.25, 95% confidence interval[CI] = 1.72-2.95), and having home rules about non-combustible tobacco use was linked to decreased likelihood of e-cigarette use (adjusted OR = 0.72, 95% CI = 0.55-0.92). The magnitude of negative association between having rules about non-combustible tobacco and adolescent e-cigarette use was stronger among adolescents with internalizing problems but weaker among those with externalizing problems. CONCLUSIONS: Our findings highlight the important role of home-based interventions in discouraging young adolescents from e-cigarette use. Parents/guardians should consider adolescents' mental health to provide more efficient home- and/or clinical-based e-cigarette use prevention.

Distribution of Extended-Spectrum-ß-Lactamase-Producing Diarrheagenic Escherichia coli Clonal Complex 10 Isolates from Patients with Diarrhea in the Republic of Korea.

ESBL-producing E. coli is a public health concern in healthcare settings and the community. Between 2009 and 2018, a total of 187 ESBL-producing pathogenic E. coli isolates were identified, and clonal complex (CC) 10 was the predominant clone (n = 57). This study aimed to characterize the ESBL-producing pathogenic E. coli CC10 strains obtained from patients with diarrhea to improve our understanding of CC10 distribution in the Republic of Korea. A total of 57 CC10 strains were selected for comprehensive molecular characterization, including serotype identification, the analysis of antibiotic resistance genes, the investigation of genetic environments, the determination of plasmid profiles, and the assessment of genetic correlations among CC10 strains. Among the CC10 isolates, the most prevalent serotype was O25:H16 (n = 21, 38.9%), followed by O6:H16 (10, 19.6%). The most dominant ESBL genes were blaCTX-M-15 (n = 31, 55%) and blaCTX-M-14 (n = 15, 27%). Most blaCTXM genes (n = 45, 82.5%) were located on plasmids, and these incompatibility groups were confirmed as IncB/O/K/Z, IncF, IncI1, and IncX1. The mobile elements located upstream and downstream mainly included ISEcp1 (complete or incomplete) and IS903 or orf477. Phylogenetic analysis showed that the CC10 strains were genetically diverse and spread among several distinct lineages. The results of this study show that ESBL-producing pathogenic E. coli CC10 has been consistently isolated, with CTX-M-15-producing E. coli O25:H16 isolates being the major type associated with the distribution of CC10 clones over the past decade. The identification of ESBL-producing pathogenic E. coli CC10 isolates underscores the possible emergence of resistant isolates with epidemic potential within this CC. As a result, continuous monitoring is essential to prevent the further dissemination of resistant ESBL-producing E. coli CC10 strains.

Dissemination of the high-risk cloneST147 carbapenem-resistant klebsiella pneumoniae from a local tertiary care hospital in the Republic of Korea.

BACKGROUND: The emergence of carbapenem-resistant Enterobacterales (CRE) infections is rapidly increasing and represents a serious public threat. In 2020, a total of 16,883 carbapenemase-producing Enterobacterales strains were collected; among these isolates, 21 strains were repeatedly isolated in a local tertiary care hospital. METHODS: Antimicrobial susceptibility testing was performed using the broth microdilution method. All 21 strains of CRKP were analyzed by PFGE after XbaI digestion. The 21 CRKP strains were sequenced on the Illumina Miseq and Oxford Nanopore GridION platforms. RESULTS: These 21 CRKP isolates showed an identical antimicrobial resistance profile, including resistance to ampicillin, carbapenems, cephems, chloramphenicol, fluoroquinolone, macrolides and trimethoprim/sulfamethoxazole. Based on whole-genome analysis, these 21 CRKP isolates shared a common genetic structure (ISAba125-IS630-blaNDM-1-bleMBL) and harbored additional resistance determinants (blaOXA-1, blaCTX-M-15, blaSHV-11, blaSHV-67, aac(6')-Ib-cr, qnrS1, OqxA, OqxB, catB3, mph(A), sul1, and dfrA12) and mutations in the quinolone resistance-determining regions of gyrA (S83I) and parC (S80I). These isolates belonged to the ST147 and KL64 capsular types, which were carried on IncFIB replicon plasmids. The 21 CRKP strains collected from one hospital were divided into five PFGE patterns, and they were closely related with a minimum similarity value of 95.2%. These isolates were found to be highly related based on the presence of between 2 and 27 SNPs. CONCLUSIONS: These findings indicate that NDM-1-producing K. pneumoniae ST147 may have been introduced via a common source, implying nosocomial transmission; furthermore, continuous monitoring is necessary to prevent endemic transmission.

Changes in children's anger, sadness, and persistence across blocked goals: Implications for self-regulation.

The current study took a person-centered approach to examine the heterogeneity of changes in children's emotions and persistence during a goal-blocking task and examined how different profiles of emotions and persistence related to children's self-regulation. Children's anger, sadness, and persistence were rated in a goal-blocking task in toddlerhood (T1; N = 140, 72 boys, Mage  = 2.67 years, 90.7% White) and preschool (T2). Children's self-regulation, specifically sustained attention and engagement, was assessed at T1, T2, and early school-age (T3) from 2005 to 2012. Growth mixture modeling revealed two classes of children at T1 and three classes at T2 with different patterns of anger, sadness, and persistence. Children's classification at T2, but not T1, significantly predicted their sustained attention and engagement both concurrently and longitudinally.

Dissemination of an international high-risk clone of Escherichia coli ST410 co-producing NDM-5 and OXA-181 carbapenemases in Seoul, Republic of Korea.

The rapid increase in carbapenemase-producing Enterobacterales is a global health concern. During 2017-2020, a total of 44 Escherichia coli isolates co-harbouring blaNDM-5 and blaOXA-181 were collected from patients at 17 hospitals in Seoul and characterized based on antimicrobial susceptibility, resistance genes and plasmid replicons detected using polymerase chain reaction (PCR). Clonal relatedness was estimated using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). All isolates had an identical multidrug resistance profile, including resistance to carbapenems, cephalosporins, ciprofloxacin, tetracycline, and trimethoprim/sulfamethoxazole, and susceptibility to amikacin, colistin, and tigecycline. Resistance genes (blaCTX-M-15, blaCMY-2, blaTEM-1B, blaOXA-1, aac(6')-Ib-cr, and qnrS) and plasmid replicons (IncFIA, IncFIB, and IncX3) was observed in almost all isolates. All isolates belonged to ST410 and were genetically similar (>88% similarity), with some PFGE types shared among isolates from different hospitals. Analysis of the whole genome revealed that the isolates clustered together with other strains of the international high-risk clone ST410 B4/H24RxC from other countries. These findings underline the ongoing spread of the high-risk clone of NDM-5- and OXA-181-producing E. coli ST410 B4/H24RxC among hospitals in Seoul. Continuous monitoring and implementation of infection control measures are crucial to track and prevent further spread of these resistant strains.

Advances in Behavioral Remote Data Collection in the Home Setting: Assessing the Mother-Infant Relationship and Infant's Adaptive Behavior via Virtual Visits.

Psychological science is struggling with moving forward in the midst of the COVID-19 pandemic, especially due to the halting of behavioral data collection in the laboratory. Safety barriers to assessing psychological behavior in person increased the need for remote data collection in natural settings. In response to these challenges, researchers, including our team, have utilized this time to advance remote behavioral methodology. In this article, we provide an overview of our group's strategies for remote data collection methodology and examples from our research in collecting behavioral data in the context of psychological functioning. Then, we describe the design and development of our strategies for remote data collection of mother-infant interactions, with the goal being to assess maternal sensitivity and intrusiveness, as well as infants' adaptive behaviors in several developmental domains. During these virtual visits over Zoom, mother-infant dyads watched a book-reading video and were asked to participate in peek-a-boo, toy play, and toy removal tasks. After the behavioral tasks, a semi-structured interview (Vineland Adaptive Behavior Scale - VABS III) was conducted to assess the infant's adaptive behavior in communication, socialization, daily living skills, and motor domains. We delineate the specific strategies we applied to integrate laboratory tasks and a semi-structured interview into remote data collection in home settings with mothers and infants. We also elaborate on issues encountered during remote data collection and how we resolved these challenges. Lastly, to inform protocols for future remote data collection, we address considerations and recommendations, as well as benefits and future directions for behavioral researchers in developmental psychology research.

Distribution of mcr genes among carbapenem-resistant Enterobacterales clinical isolates: high prevalence of mcr-positive Enterobacter cloacae complex in Seoul, Republic of Korea.

Colistin is often used as a drug of last resort against infections caused by multi-drug-resistant Gram-negative bacteria, including carbapenem-resistant Enterobacterales (CRE). Recently, the acquisition of mobile colistin resistance (mcr) genes by CRE has become a cause for concern. This study investigated the prevalence of mcr genes in CRE isolates in Seoul, Republic of Korea. In total, 3675 CRE strains were collected from patients between 2018 and 2019, and initially screened for mcr genes using multiplex polymerase chain reaction assays. Upon the identification of mcr-harbouring strains, colistin susceptibility tests, identification of carbapenemase and ß-lactamase genes, and plasmid replicon typing were performed. Clonal analysis was conducted using pulsed-field gel electrophoresis. mcr genes were detected in 2.2% (80/3675) of CRE strains. There were three mcr-1 carriers, one mcr-4.3 carrier, one mcr-4.3/mcr-9 carrier, 58 mcr-9 carriers, one mcr-9/mcr-10 carrier and 16 mcr-10 carriers among various Enterobacterales species, of which 60 were Enterobacter cloacae complex (ECC) strains. The prevalence of mcr genes in ECC strains was 20.5%. Molecular detection confirmed that 21.3% and 13.8% of mcr-harbouring strains shared blaNDM-1 or blaKPC-2, respectively. In addition, an IncHI2 replicon was identified in 71.7% of mcr-9 strains. Comparative analysis revealed not only a notable diversity of mcr carriers, but also clonal spreading or nosocomial outbreaks of some ECC strains. These findings revealed a silent distribution of mcr genes in CRE strains with high genetic heterogeneity in Seoul, underscoring the urgent need for timely intervention to control and prevent mcr dissemination.

Why do parents use screen media with toddlers? The role of child temperament and parenting stress in early screen use.

Considering child characteristics may be an important piece to understanding parental decision-making for children's screen use. The current cross-sectional study examined the mediating role of maternal parenting stress in the relation of child temperament to young children's screen use. Recognizing the multidimensional aspects of temperament, three mediated pathways for three temperament domains (i.e., negative affectivity, surgency, and effortful control) were tested. Mothers of toddlers, 18-36 months (N = 296), completed an online survey, reporting on child temperament, total parenting stress, and child screen use. The results showed that mother-child dynamics were related to toddlers' screen use. Toddlers' negative affectivity and effortful control were each associated with toddlers' screen use through maternal parenting stress. Higher negative affectivity was associated with higher maternal parenting stress, which in turn, was related to greater screen use in toddlers. Toddlers' lower effortful control was related to higher maternal parenting stress, which in turn, was associated with greater screen use. Toddlers' surgency was not related to either maternal parenting stress or toddlers' screen use. The findings from this study contribute to an understanding of media-related parenting in toddlerhood and may help with the development of strategies for supporting healthy media habits in families with young children.

Emerging high-level ciprofloxacin-resistant Salmonella enterica serovar typhi haplotype H58 in travelers returning to the Republic of Korea from India.

In Korea, typhoid fever is a rare disease due to improved living standards. However, typhoid fever remains a major burden in developing countries and regions, such as India and Southeast Asia. In this study, we isolated Salmonella Typhi (S. Typhi) from eight patients with typhoid fever who were travelers returning from India. The strains isolated were characterized by antimicrobial susceptibility profiling and whole-genome sequencing (WGS) analysis. All strains were resistant to nalidixic acid and azithromycin. Among them, four isolates were highly resistant to ciprofloxacin (MIC ≥32 µg/ml); these strains have not been confirmed in Korea PulseNet DB. According to WGS, the ciprofloxacin-resistant strains belong to the global dominant multidrug-resistant (MDR) haplotype H58 (SNP glpA C1047T, SptP protein Q185* (premature stop codon)) and do not harbor the MDR plasmid. H58-associated SNPs in membrane and metabolism genes, including yhdA, yajI, hyaE, tryE, rlpB and metH, are present. Additionally, phylogenetic analysis assigned the H58 strains to sublineage II, whereas the non-H58 strains are closely related to haplotype H50. The presence of high-level ciprofloxacin-resistant S. Typhi haplotype H58 in Korea was first confirmed as due to influx from overseas via travelers. This study provides information about intercontinental drug-resistant transmission between countries and suggests that travelers need to be careful about personal hygiene.

Co-infection With Chromosomally-Located bla CTX-M-14 and Plasmid-Encoding bla CTX-M-15 in Pathogenic Escherichia coli in the Republic of Korea.

The emergence of third-generation cephalosporin resistance in Escherichia coli is increasing at an alarming rate in many countries. Thus, the aim of this study was to analyze co-infecting bla CTX-M-producing pathogenic E. coli isolates linked to three school outbreaks. Among 66 E. coli isolates, 44 were identified as ETEC O25, an ETEC isolate serotype was O2, and the other 21 were confirmed as EAEC O44. Interestingly, six patients were co-infected with EAEC O44 and ETEC O25. For these isolates, molecular analysis [antibiotic susceptibility testing, identification of the ß-lactamase gene, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE)] was performed for further characterization. In addition, the transmission capacity of bla CTX-M genes was examined by conjugation experiments. Whole-genome sequencing (WGS) was performed on representative EAEC O44 and ETEC O25 isolates associated with co-infection and single-infection. All isolates were resistant to cefotaxime and ceftriaxone. All EAEC isolates carried the bla CTX-M-14 gene and all ETEC isolates the bla CTX-M-15 gene, as detected by multiplex PCR and sequencing analysis. Sequence type and PFGE results indicated three different patterns depending on the O serotype. WGS results of representative isolates revealed that the ETEC O25 strains harbored bla CTX-M-15 located on IncK plasmids associated with the Δbla TEM-bla CTX-M-15-orf477 transposon. The representative EAEC O44 isolates carried bla CTX-M-14 on the chromosome, which was surrounded by the ISEcp1-bla CTX-M-14-IS903 transposon. To the best of our knowledge, this is the first report of co-infection with chromosomally located bla CTX-M-14 and plasmid-encoding bla CTX-M-15 in pathogenic E. coli. Our findings indicate that resistance genes in clinical isolates can spread through concurrent combinations of chromosomes and plasmids.

Yield Stress Enhancement of a Ternary Colloidal Suspension via the Addition of Minute Amounts of Sodium Alginate to the Interparticle Capillary Bridges.

Capillary suspensions are ternary solid-liquid-liquid systems produced via the addition of a small amount of secondary fluid to the bulk fluid that contained the dispersed solid particles. The secondary fluid could exert strong capillary forces between the particles and dramatically change the rheological properties of the suspension. So far, research has focused on capillary suspensions that consist of additive-free fluids, whereas capillary suspensions with additives, particularly those of large molecular weight that are highly relevant for industrial purposes, have been relatively less studied. In this study, we performed a systematic analysis of the properties of capillary suspensions that consist of paraffin oil (bulk phase), water (secondary phase), and α-Al2O3 microparticles (particle phase), in which the aqueous secondary phase contained an important eco-friendly polymeric binder, sodium alginate (SA). It was determined that the yield stress of the suspension increased significantly with the increase in the SA content in the aqueous secondary phase, which was attributed to the synergistic effect of the capillary force and hydrogen bonding force that may be related to the increase in the number of capillary bridges. The amounts of SA used to induce a significant change in the yield stress in this study were very small (<0.02% of the total sample volume). The addition of Ca2+ ions to the SA-containing secondary phase further increased the yield stress with possible gelation of the SA chains-in the presence of excess Ca2+ ions, however, the yield stress decreased because of the microscopic phase separation that occurred in the aqueous secondary phase. The microstructures of the sintered porous materials that were produced by using capillary suspensions as precursors were qualitatively well correlated to the rheological behavior of the precursor suspensions, suggesting a new method for the subtle control of the microstructures of porous materials using the addition of minute amounts of polymeric additives.

Arsenic induces platelet shape change through altering focal adhesion kinase-mediated actin dynamics, contributing to increased platelet reactivity.

Arsenic, an environmental contaminant in drinking water worldwide is well-established to increase cardiovascular diseases (CVDs) in humans. Of these, thrombotic events represent a major adverse effect associated with arsenic exposure, for which an abundance of epidemiological evidence exists. Platelet aggregation constitutes a pivotal step in thrombosis but arsenic alone doesn't induce aggregation and the mechanism underlying arsenic-induced thrombosis still remains unclear. Here we demonstrated that arsenic induces morphological changes of platelets, i.e., contraction and pseudopod projection, the primal events of platelet activation, which can increase platelet reactivity. Arsenite induced prominent platelet shape changes in a dose-dependent manner in freshly isolated human platelets. Of note, arsenite suppressed focal adhesion kinase (FAK) activity, which in turn activated RhoA, leading to altered actin assembly through LIMK activation, and subsequent cofilin inactivation. Arsenic-induced platelet shape change appeared to increase the sensitivity to thrombin and ADP-induced aggregation. Supporting this, latrunculin A, an inhibitor of actin-dynamics abolished it. Taken together, we demonstrated that arsenic induces cytoskeletal changes and shape changes of platelets through FAK-mediated alteration of actin dynamics, which renders platelets reactive to activating stimuli, ultimately contributing to increased thrombosis.

Traveller-associated high-level ciprofloxacin-resistant Salmonella enterica Serovar Kentucky in the Republic of Korea.

OBJECTIVE: Salmonella enterica serotype Kentucky ST198 (S. Kentucky) is frequently associated with human infections and has been identified in travellers to North Africa, South Asia, Europe, and North America. The antimicrobial resistance of this serotype to multiple drugs, including ciprofloxacin (CIP), is a growing concern. However, little information is available regarding the occurrence and characterization of S. Kentucky in Korea. METHODS: To investigate the characteristics and possible origin of these infections, we characterized highly CIP-resistant S. Kentucky isolates collected through a national surveillance program. Single-nucleotide polymorphisms (SNPs) were identified by whole-genome sequencing (WGS), and genome sequencing was performed to investigate the genetic relationships and resistance mechanisms of the isolates. RESULTS: Ten CIP-resistant S. Kentucky strains were isolated from diarrheal patients in Korea from 2008 to 2017. The travel histories of the patients indicated that seven had returned from Southeast Asia. WGS of all the isolates revealed the presence of Salmonella genomic island 1 (SGI1) and substitutions in the gyrA and parC genes, which are known to confer resistance to CIP. A multilocus sequence type (MLST) analysis revealed that the isolates belonged to ST198, which has been prevalent in Europe and Africa. Furthermore, a phylogenetic analysis showed that all 10 isolates shared close genetic relationships. CONCLUSIONS: We report the identification of S. Kentucky in Korea through long-term surveillance. International travel, especially to Southeast Asia, has been a major risk factor for human infections of CIP-resistant S. Kentucky in Korea.

The role of international travellers in the spread of CTX-M-15-producing Shigella sonnei in the Republic of Korea.

BACKGROUND: Multidrug-resistant Shigella isolates have recently emerged as a serious public health threat worldwide. In particular, overseas travel is a risk factor for acquisition of antimicrobial-resistant Shigella strains. To explore the role of travel in the spread of cefotaxime-resistant Shigella sonnei in Korea, we screened 751 Shigella spp. isolates from 2007 to 2016 through the National Surveillance system, and 28 cephalosporin-resistant S. sonnei isolates were identified. METHODS: For cephalosporin-resistant S. sonnei isolates, epidemiological and molecular analyses (plasmid structure analysis, pulsed-field gel electrophoresis (PFGE) and high-quality single-nucleotide polymorphisms (hqSNPs) based on whole-genome sequencing (WGS)) were conducted to investigate the source of infection and transmission route. RESULTS: Among the 28 cefotaxime-resistant S. sonnei strains, 18 were isolated from travellers returning from Asia, including Vietnam (n=11). Molecular analysis of 18 blaCTX-M-type isolates revealed that 15 contain CTX-M-15; 50% of isolates from domestic patients contain CTX-M-14. Analysis of the genetic environments of the blaCTX-M-14 and blaCTX-M-15 genes revealed different genetic organization surrounding the blaCTX-M genes. Additionally, PFGE and hqSNP results suggested a large phylogenetic distance between the S. sonnei isolates related to overseas travel and those acquired domestically in Korea. CONCLUSION: Our study data demonstrates that two prevalent blaCTX-M genes, blaCTX-M-14 and blaCTX-M-15, have been circulating in S. sonnei in Korea over the last 10 years. Recently, international travellers are at a high risk for acquisition of CTX-M-15-producing S. sonnei in Korea.

Incremental Treatment Costs Attributable to Overweight and Obesity in Patients with Diabetes: Quantile Regression Approach.

OBJECTIVE: This study aimed to estimate treatment costs attributable to overweight and obesity in patients with diabetes who were less than 65 years of age in the United States. METHODS: This study used data from the Medical Expenditure Panel Survey from 2001 to 2013. Patients with diabetes were identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code (250), clinical classification codes (049 and 050), or self-reported physician diagnoses. Total treatment costs attributable to overweight and obesity were calculated as the differences in the adjusted costs compared with individuals with diabetes and normal weight. Adjusted costs were estimated by using generalized linear models or unconditional quantile regression models. RESULTS: The mean annual treatment costs attributable to obesity were $1,852 higher than those attributable to normal weight, while costs attributable to overweight were $133 higher. The unconditional quantile regression results indicated that the impact of obesity on total treatment costs gradually became more significant as treatment costs approached the upper quantile. CONCLUSIONS: Among patients with diabetes who were less than 65 years of age, patients with diabetes and obesity have significantly higher treatment costs than patients with diabetes and normal weight. The economic burden of diabetes to society will continue to increase unless more proactive preventive measures are taken to effectively treat patients with overweight or obesity.