Measuring the Burden of Disease in Korea

This paper provides an overview of the Korean Burden of Disease (KBoD) study, which was the first such study to assess the national burden of disease using disability-adjusted life years (DALYs) in an advanced Asian country. The KBoD study generally followed the approach utilized in the original Global Burden of Disease study (GBD), with the exception of the disease classification and epidemiological data estimation methods used, and the relative weightings of disabilities. The results of the present study reveal that the burden of disease per 100,000 of the Korean population originates primarily from; cancer (1,525 Person Years, PYs), cardiovascular disease (1,492 PYs), digestive disease (1,140 PYs), diabetes mellitus (990 PYs), and certain neuro-psychiatric conditions (883 PYs). These results are largely consistent with those of developed countries, but also represent uniquely Korean characteristics

Effect of Iron-Chelator Deferiprone on the In Vitro Growth of Staphylococci

The standard iron-chelator deferoxamine is known to prevent the growth of coagulase-negative staphylococci (CoNS) which are major pathogens in iron-overloaded patients. However, we found that deferoxamine rather promotes the growth of coagulase-positive Staphylococcus aureus. Accordingly, we tested whether deferiprone, a new clinically-available iron-chelator, can prevent the growth of S. aureus strains as well as CoNS. Deferiprone did not at least promote the growth of all S. aureus strains (n=26) and CoNS (n=27) at relatively low doses; moreover, it could significantly inhibit the growth of all staphylococci on non-transferrin-bound-iron and the growth of all CoNS on transferrin-bound iron at relatively high doses. At the same doses, it did not at least promote the growth of all S. aureus strains on transferrin-bound-iron. These findings indicate that deferiprone can be useful to prevent staphylococcal infections, as well as to improve iron overload, in iron-overloaded patients

Differences in Clinical Features According to Boryoung and Karp Genotypes of Orientia tsutsugamushi

Scrub typhus is an infectious disease caused by Orientia tsutsugamushi. The differences in virulence of O. tsutsugamushi prototypes in humans are still unknown. We investigated whether there are any differences in the clinical features of the Boryoung and Karp genotypes.Patients infected with O. tsutsugamushi, as Boryoung and Karp clusters, who had visited 6 different hospitals in southwestern Korea were prospectively compared for clinical features, complications, laboratory parameters, and treatment responses. Infected patients in the Boryoung cluster had significantly more generalized weakness, eschars, skin rashes, conjunctival injection, high albumin levels, and greater ESR and fibrinogen levels compared to the Karp cluster. The treatment response to current antibiotics was significantly slower in the Karp cluster as compared to the Boryoung cluster.The frequency of occurrence of eschars and rashes may depend on the genotype of O. tsutsugamushi

The Central PXXP Motif Is Crucial for PMAP-23 Translocation across the Lipid Bilayer

PMAP-23, a cathelicidin-derived host defense peptide, does not cause severe membrane permeabilization, but exerts strong and broad-spectrum bactericidal activity. We have previously shown that it forms an amphipathic α-helical structure with a central hinge induced by the PXXP motif, which is implicated in the interaction of PMAP-23 with negatively charged bacterial membranes. Here, we studied the potential roles of the PXXP motif in PMAP-23 translocation across the lipid bilayer by replacing Pro residues with either α-helix former Ala (PMAP-PA) or α-helix breaker Gly (PMAP-PG). Although both PMAP-PA and PMAP-PG led to effective membrane depolarization and permeabilization, they showed less antimicrobial activity than wild-type PMAP-23. Interestingly, we observed that PMAP-23 crossed lipid bilayers much more efficiently than its Pro-substituted derivatives. The fact that the Gly-induced hinge was unable to replace the PXXP motif in PMAP-23 translocation suggests that the PXXP motif has unique structural properties other than the central hinge. Surface plasmon resonance sensorgrams showed that the running buffer almost entirely dissociated PMAP-23 from the membrane surface, while its Pro-substituted derivatives remained significantly bound to the membrane. In addition, kinetic analysis of the sensorgrams revealed that the central PXXP motif allows PMAP-23 to rapidly translocate at the interface between the hydrophilic and hydrophobic phases. Taken together, we propose that the structural and kinetic understanding of the PXXP motif in peptide translocation could greatly aid the development of novel antimicrobial peptides with intracellular targets by promoting peptide entry into bacterial cells

Effect of central PxxP motif in amphipathic alpha-helical peptides on antimicrobial activity and mode of action

Abstract Amphipathic α-helical peptides (AHPs) have shown potential as a therapeutic approach against multi-drug-resistant bacterial infections due to their broad-spectrum antimicrobial activity by disrupting bacterial membranes. However, their nonspecific interactions with membranes often result in cytotoxicity toward mammalian cells. Previous studies have shown that a PxxP motif near the middle of cathelicidin-derived antimicrobial peptides contributes to potent and selective antibacterial activity. In this study, we compared KL18 with KL-PxxP to examine the effects of the central PxxP motif in AHPs on their structure, antibiotic activity, and mode of action. In a membrane-mimetic environment, we observed that KL18 had a much higher helical content compared to KL-PxxP. In aqueous buffer, KL18 adopted a highly ordered α-helical conformation, while KL-PxxP exhibited a disordered conformation. We found that KL-PxxP exhibited 4–16 times higher antibacterial activity than KL18 and significantly reduced the hemolytic activity. These findings suggest that the dynamic conformational behaviors caused by the central PxxP motif conferred the antibacterial selectivity of AHPs. Additionally, KL-PxxP showed strong binding to anionic liposomes and weak binding to zwitterionic liposomes, explaining its selectivity for bacteria over mammalian cells. Despite having a low ability to dissipate the bacterial membrane potential, KL-PxxP translocated efficiently across lipid membranes. Therefore, we propose that the central PxxP motif in AHPs provides dynamic conformational behavior in aqueous and membrane-mimetic environments, enhances binding to anionic membranes, and facilitates translocation across lipid bilayers, resulting in improved antibacterial potency and selectivity. Understanding the unique structural characteristics and functional roles of the PxxP motif in the antimicrobial mechanism of action holds great potential for advancing the development of novel peptide antibiotics

Development of quality management systems for clinical practice guidelines in Korea

This study introduces the Clinical practice guidelines (CPGs) appraisal system by the Korean Academy of Medical Sciences (KAMS). Quality management policies for CPGs vary among different countries, which have their own cultures and health care systems. However, supporting developers in guideline development and appraisals using standardized tools are common practices. KAMS, an organization representing the various medical societies of Korea, has been striving to establish a quality management system for CPGs, and has established a CPGs quality management system that reflects the characteristics of the Korean healthcare environment and the needs of its users. KAMS created a foundation for the development of CPGs, set up an independent appraisal organization, enacted regulations related to the appraisals, and trained appraisers. These efforts could enhance the ability of each individual medical society to develop CPGs, to increase the quality of the CPGs, and to ultimately improve the quality of the information available to decision-makers

Understanding the thermal instability of fluoroethylene carbonate in LiPF6-based electrolytes for lithium ion batteries

The cycling and storage performances of LiCoO2 (LCO)-LiNi0.5Co0.2Mn0.3O2 (NCM)/pitch-coated silicon alloy-graphite (Si-C) full cells with ethylene carbonate (EC)-based and fluoroethylene carbonate (FEC)-based electrolytes are investigated at elevated temperatures. Excess FEC (used as a co-solvent in LiPF6-based electrolytes), which is not completely consumed during the formation of the solid electrolyte interphase (SEI) layer on the electrodes, is prone to defluorination in the presence of Lewis acids such as PF5; this reaction can generate unwanted HF and various acids (H3OPF6, HPO2F2, H2PO3F, H3PO4) at elevated temperatures. Our investigation reveals that the HF and acid compounds that are formed by FEC decomposition causes significant dissolution of transition metal ions (from the LCO-NCM cathode) into the electrolyte at elevated temperatures; as a result, the reversible capacity of the full cells reduces because of the deposition of the dissolved metal ions onto the anode. Moreover, we demonstrate possible mechanisms that account for the thermal instability of FEC in LiPF6-based electrolytes at elevated temperatures using model experiments.ope