Search

This study aims to investigate the effect of electronic stimulation (ES) as a non-pharmacological treatment in restless legs syndrome (RLS). This is a randomized, single-blind study. A total of 46 patients were included, consisting of an active group and a sham group with 22 and 24 members, respectively. The stimulation was administered to bilateral lower legs using the tapping mode (3 Hz) on a handheld ES device, and symptom changes were measured in both groups. The effects of the stimuli were analyzed with repeated measures ANOVA. The symptom severity was significantly reduced in the active group, and showed significant interaction effects in the time * group (F = 4.441, p = 0.031). Although both the active and sham groups reported improved symptoms upon receiving longer periods of treatment, the effect of the ES was greater in the active group. ES treatment resulted in symptom improvement when using ideal levels of stimulation intensity. ES can be considered as a non-pharmacological treatment option for RLS. [ABSTRACT FROM AUTHOR]

Objectives: Resting-state brain connectivity has been shown to differ for Restless Legs Syndrome (RLS) compared to healthy control (CON) groups. This study evaluates the degree these RLS-CON differences are changed by concurrent treatment.Methods: Resting-state functional MRIs were obtained from 32 idiopathic RLS patients during the morning asymptomatic period and 16 age and gender-matched CON subjects. Of the 32 RLS patients, 16 were drug-naïve (DN-RLS), and 16 were regularly drug-treated using a dopamine agonist (DT-RLS). Various assessments of disease characteristics were also performed. The primary purpose was to assess the replicability of prior results and the effects of treatment on these differences between controls and untreated RLS patients. Resting-state connectivity was analyzed by a seed-based method using the bilateral ventral-posterolateral nuclei (VPLN) in the thalamus.Results: In the DN-RLS group, compared to the CON group, three areas (the bilateral lingual gyri and right middle temporal gyrus) were replicated. The three replicated areas did not significantly differ for DT-RLS compared to DN-RLS. DT-RLS compared to DN-RLS had significantly higher thalamic connectivity for the left uvula, right tuber, left anterior insula, and right declive.Conclusions: Thalamic connectivity to the bilateral lingual gyri and right middle temporal gyrus is a replicable finding in DN-RLS that was not affected by dopamine agonist treatments. Other changes in thalamic connectivity were altered by dopamine agonist treatment. These treatment effects may be pertinent to the known treatment benefits of a dopamine agonist on RLS symptoms. [ABSTRACT FROM AUTHOR]

Background: Rabies is a major public health problem with a fatality rate close to 100%; however, complete prevention can be achieved through pre- or post-exposure prophylaxis. The rapid fluorescent focus inhibition test (RFFIT) is one of the recommended testing methods to determine the production of neutralizing antibodies after vaccination. Here, we report the development of a new monoclonal antibody (mAb) designed to react specifically with Rabies virus (RABV) phosphoprotein (P protein), and the evaluation of its applicability to the RFFIT and its effectiveness as a diagnostic reagent for human rabies. Methodology/principal findings: The mAb KGH P 16B8 was produced to target the P protein of the Korean KGH RABV strain. An indirect immunofluorescence assay (IFA) was conducted to detect various strains of RABV in various cell lines. Alexa-conjugated KGH P 16B8 (16B8-Alexa) was developed for the RFFIT. The IFA test could detect RABV up to a 1:2,500 dilution, with a detection limit comparable to that of a commercial diagnostic reagent. The sensitivity, specificity, positive predictive value, and negative predictive value of the RFFIT using 16B8-Alexa in 414 clinical specimens were 98.67%, 99.47%, 99.55%, and 98.42%, respectively. The results of the RFFIT with 16B8-Alexa were strongly correlated with those obtained using an existing commercial diagnostic reagent (r = 0.995, p<0.001). Conclusions/significance: The mAb developed in this study shows high sensitivity and specificity, confirming its clinical utility with the RFFIT to measure the rabies neutralizing antibody titer and establish a diagnosis in human. Thus, 16B8-Alexa is expected to serve as an alternative diagnostic reagent that is widely accessible, with potentially broad applications beyond those of the RFFIT in Korea. Further studies with 16B8-Alexa should provide insight into the immunological mechanism of the P protein of Korean RABV. [ABSTRACT FROM AUTHOR]

Neisseria gonorrhoeae is an obligate human pathogen that is the etiological agent of gonorrhea. We explored variations in the genes of a multidrug-resistant N. gonorrhoeae isolate from a Korean patient in an effort to understand the prevalence, antibiotic resistance, and importance of horizontal gene transfer within this important, naturally competent organism. Here, we report the complete annotated genome sequence of N. gonorrhoeae strain NCCP11945.

Prion propagation is mediated by the structural alteration of normal prion protein (PrPC) to generate pathogenic prion protein (PrPSc). To date, compounds for the inhibition of prion propagation have mainly been screened using PrPSc-infected cells. Real time–quaking-induced conversion (RT-QuIC) is one alternative screening method. In this study, we assessed the propagation inhibition effects of known anti-prion compounds using RT-QuIC and compared the results with those from a PrPSc-infected cell assay. Compounds were applied to RT-QuIC reactions at 0 h or 22 h after prion propagation to determine whether they inhibited propagation or reduced amplified aggregates. RT-QuIC reactions in presence of acridine, dextran sulfate sodium (DSS), and tannic acid inhibited seeded aggregation with sporadic Creutzfeldt-Jakob disease at 0 h. After treatment at 22 h, amplified fluorescence was decreased in wells treated with either acridine or tannic acid. Compound activities were verified by western blot of RT-QuIC products and in a dye-independent conversion assay, the Multimer Detection System. Protease K-resistant PrPSc fragments (PrPres) were reduced by DSS and tannic acid in the PrPSc-infected cell assay. Importantly, these inhibitory effects were similar despite different treatment times (0 h versus 3 days). Consequentially, RT-QuIC enabled the more specific classification of compounds according to action (i.e., inhibition of prion propagation versus reduction of amplified aggregates). RT-QuIC addresses the limitations of cell-based screening methods and can be used to further aid our understanding of the mechanisms of action of anti-prion compounds. [ABSTRACT FROM AUTHOR]

Inherited prion diseases (IPDs), including genetic Creutzfeldt-Jakob disease (gCJD), account for 10–15% of cases of prion diseases and are associated with several pathogenic mutations, including P102L, V180I, and E200K, in the prion protein gene (PRNP). The valine to isoleucine substitution at codon 180 (V180I) of PRNP is the most common pathogenic mutation causing gCJD in East Asian patients. In this study, we conducted follow-up analyses to identify candidate factors and their associations with disease onset. Whole-genome sequencing (WGS) data of five gCJD patients with V180I mutation and 145 healthy individuals were used to identify genomic differences. A total of 18,648,850 candidate variants were observed in only the patient group, 29 of them were validated as variants. Four of these validated variants were nonsense mutations, six were observed in genes directly or indirectly related to neurodegenerative disorders (NDs), such as LPA, LRRK2, and FGF20. More than half of validated variants were categorized in Gene Ontology (GO) terms of binding and/or catalytic activity. Moreover, we found differential genome variants in gCJD patients with V180I mutation, including one uniquely surviving 10 years after diagnosis of the disease. Elucidation of the relationships between gCJD and Alzheimer’s disease or Parkinson’s disease at the genomic level will facilitate further advances in our understanding of the specific mechanisms mediating the pathogenesis of NDs and gold standard therapies for NDs. [ABSTRACT FROM AUTHOR]

Successful empirical therapy of Staphylococcus aureus infections requires the ability to predict methicillin resistance. Our aim was to identify predictors of methicillin resistance in community-onset (CO) invasive S. aureus infections. Sixteen hospitals across Korea participated in this study from May to December 2012. We prospectively included cases of S. aureus infection in which S. aureus was isolated from sterile clinical specimens ≤72 hours after hospitalization. Clinical and epidemiological data were gathered and compared in methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) cases. Community-associated (CA) infections were defined as in previous studies. In total, there were 786 cases of community-onset S. aureus infection, 102 (13.0%) of which were CA-MRSA. In addition to known risk factors, exposure to 3rd generation cephalosporins in the past 6 months [odds ratio (OR), 1.922; 95% confidence interval (CI), 1.176–3.142] and close contact with chronically ill patients in the past month (OR, 2.647; 95% CI, 1.189–5.891) were independent risk factors for MRSA infection. However, no clinical predictors of CA-MRSA were identified. Methicillin resistance, CO infection, and appropriateness of empirical antibiotics were not significantly related to 30-day mortality. MRSA infection should be suspected in patients recently exposed to 3rd generation cephalosporins or chronically-ill patients. There were no reliable predictors of CA-MRSA infection, and mortality was not affected by methicillin resistance. [ABSTRACT FROM AUTHOR]

PCR fingerprinting and multilocus sequence typing were applied to determine the major molecular types of the Cryptococcus neoformans/ Cryptococcus gattii species complex in the Republic of Korea. Of the 78 strains isolated from patients diagnosed with cryptococcosis between 1990 and 2008, 96% were C. neoformans serotype A, mating type MATα and molecular type VNI. The remaining 4% were C. gattii, serotype B, mating type MATα and either molecular type VGIIb or VGIII. Of the 62 strains with known HIV status, only 14 (22.6%) were isolated from HIV-positive patients and belonged to molecular type VNI. Remarkably, 93% of the C. neoformans isolates had identical PCR fingerprint profiles with the VNIc genotype that has been identified recently as the major genotype among C. neoformans strains in China. Most strains (81.8%) of the VNIc genotype were associated with non-HIV patients compared with strains of the non-VNIc genotype (20%) ( P=0.009). Unlike the Chinese strains, a majority (60%) of the non-HIV patients infected with strains of the VNIc genotype in the Republic of Korea had serious underlying conditions, with cancer and liver disease being the most common. This study affirms VNIc to be the most prevalent genotype of C. neoformans isolated from non-HIV patients with cryptococcosis. [ABSTRACT FROM AUTHOR]

We investigated the species distribution and antifungal susceptibility of Candida isolates from tertiary and non-tertiary hospitals in South Korea from 2002-2004. Of the 612 Candida isolates that were collected, Candida albicans, C. parapsilosis, C. tropicalis, and C. glabrata occurred most frequently, accounting for 97.3% and 96.8% of the isolates in tertiary and non-tertiary hospitals, respectively. C. albicans was the most common isolate, but the incidence of non-C. albicans Candida species was higher than that of C. albicans in tertiary hospitals. The Candida species had much lower MIC90 to voriconazole (tertiary hospitals: 0.5 µg/ml, non-tertiary hospitals: 0.25 µg/ml) than to fluconazole (tertiary hospitals: 8 µg/ml, non-tertiary hospitals: 4 µg/ml). The MIC90 of Candida isolates to 5-flucytosine in non-tertiary hospitals was two times higher than that observed in tertiary facilities. The C. glabrata isolates showed a tendency toward strong resistance to fluconazole, but C. parapsilosis isolates were susceptible to all of the evaluated antifungal agents. Voriconazole showed strong in vitro activity against Candida species, especially C. krusei, which is resistant to fluconazole and 5-flucytosine. To our knowledge, this is the first report of Candida antifungal susceptibility that includes non-tertiary hospitals in South Korea. [ABSTRACT FROM AUTHOR]

Abstract: The presence of fluoroquinolone resistance-associated alterations in topoisomerase II and IV were investigated for 103 nfxC-like type Pseudomonas aeruginosa isolates. The most nfxC-like type isolates (98.1%) possessed the substitution of Ile for Thr-83 in GyrA. A single alteration in GyrA (Thr-83→Ile) was the most frequently detected and the next common alteration was two alterations with Thr-83→Ile in GyrA and Ser-87→Leu in ParC. A novel alteration at position Glin-106 of GyrA, which was suggested to be responsible for fluoroquinolone resistance, was identified. Our study revealed that the alterations in GyrB (Glu-468→Asp) and in ParE (Asp-419→Asn or Glu-459→Asp) play a complementary role in the acquisition of resistance to fluoroquinolone. There was a correlation between the ciprofloxacin MIC and the number of resistance-associated alterations in GyrA, GyrB, ParC and ParE of P. aeruginosa isolates. [Copyright &y& Elsevier]

Background: Despite the importance of invasive Staphylococcus aureus (ISA) infection, its overall burden in non-selected populations has only been defined in a small number of studies in Europe and North America. To define the characteristics of ISA infections in Korea, we conducted a multi-center cohort study to estimate population-based incidence rates.Methods: We conducted a multicenter prospective cohort study at nine university-affiliated active-surveillance core centers (ASCs) in three regions of Korea. To cover all available clinical microbiologic laboratories, we classified the laboratories in these regions into three groups according to their clinical environment as: 1) Nine ASCs, 2) Five major commercial laboratories and 3) Forty-four acute-care hospital-affiliated microbiology laboratories. We requested all the laboratories to report prospectively their numbers of cases of S. aureus isolated from normally sterile sites. Detailed clinical information was collected about the cases in the nine ASCs.Results: From 1 July 2009 to 30 June 2011, a total of 1,198 cases of ISA infection were identified at the nine ASCs, including 748 (62%) methicillin-resistant S. aureus (MRSA) infections. Most (81%) ISA infections were healthcare-associated (HCA): 653 (55%) hospital-onset and 322 (27%) community-onset. 223 (19%) were community-associated infections. The most common primary diagnosis was catheter-associated infection (225 cases, 19%). Respiratory tract infection (160, 13%), skin & soft tissue (152, 13%) and bone & joint infections (120, 10%) were also common. 30-day and 12-week mortality rates were 25.6% (262/1,024) and 36.5% (314/860), respectively. Complications, including metastatic infection within 12 weeks, occurred in 17.8% of ISA infections. The most common site of metastatic infection was the lung (9.8%, 84/860). Based on the total of 2,806 observed cases of ISA infection, estimated annual rates of ISA and invasive MRSA infections were 43.3 and 27.7 per 100,000 populations, respectively.Conclusions: Our data provide important information about the clinical characteristics of ISA infections. We estimate that over 21,000 ISA infections and 13,000 invasive MRSA infections occurred in Korea in 2010. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to quantify the biofilm formations of various methicillin-resistant Staphylococcus aureus (MRSA) clones (ST1, ST5, ST72, ST89, ST239, and ST254) and to evaluate the in vitro activities of antibiotics. Of 86 MRSA isolates tested, 44 isolates (51.2 %) formed biofilms, including 8 strong biofilm producers (7 isolates of ST72 and 1 isolate of ST89). The planktonic MICs, minimal bactericidal concentrations, and minimum biofilm eradication concentrations (MBECs) of 6 antibiotics (clindamycin, gentamicin, linezolid, vancomycin, daptomycin, and tigecycline) were measured for 8 MRSA isolates. The planktonic isolates were susceptible to all agents, with daptomycin being the most effective, followed by gentamicin and vancomycin. However, clindamycin, linezolid, and tigecycline showed bacteriostatic activity against most of the isolates. The biofilms were resistant to high concentrations of most drugs. However, the MBEC values of daptomycin and tigecycline were lower overall than that of other antibiotics. Microscopy studies verified that daptomycin was the most effective drug used in adhesive biofilms, while gentamicin and tigecycline exhibited some bactericidal efficacy. Our results demonstrated that ST72 and ST89 form strong biofilms that may cause problems in hospital setting, and daptomycin, gentamicin, and tigecycline may be choice therapeutics against biofilm-mediated S. aureus infections. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate for the first time the prevalence and types of extended-spectrum β-lactamase (ESBL) and plasmid-mediated AmpC β-lactamase (PABL) in Enterobacteriaceae in Korean long-term care facilities (LTCFs). ESBL rates were 45.3% (72/159) in Escherichia coli and 42.7% (50/117) in Klebsiella pneumoniae. In E. coli, CTX-M-28, the most prevalent ESBLs, was identified for the first time in Korea in 44 isolates. In K. pneumoniae, SHV-12 was found in 27 isolates (52.9% of ESBLs), among which 25 isolates also contained SHV-11. Twenty-seven isolates had SHV and CTX-M β-lactamase simultaneously. PABL genes were detected in 39.3% (46/117) of K. pneumoniae and 3.1% (5/159) E. coli. In E. coli, DHA-1(3), CMY-2(1), and CMY-6(1) were detected, whereas in K. pneumoniae, only DHA-1 was detected. Among the PABL-producing organisms, 80.0% (E. coli) and 52.2% (K. pneumoniae) simultaneously produced ESBLs. In conclusion, LTCF residents in Korea have a very high prevalence of E. coli and K. pneumoniae producing ESBLs, PABLs, or both, and the genotypes of ESBL and PABL were identical with those found in general hospitals. [Copyright &y& Elsevier]

Abstract: A nationwide surveillance of the antimicrobial resistance of Pseudomonas aeruginosa isolates from non-tertiary care hospitals was conducted in Korea from 2002 to 2006. Resistance to almost all antimicrobial agents decreased significantly from 2003 (P < 0.01). Resistance rates to the major antipseudomonal agents, ceftazidime, imipenem, meropenem, and aztreonam, were 18.8%, 20.5%, 18.7%, and 19.7%, respectively, in 2003. However, they had all decreased to below 10% in 2006. The proportion of multidrug-resistant isolates that were resistant to at least 3 of 5 major antipseudomonal agent decreased from 33.5% in 2003 to 23.1% in 2006 (P < 0.05). In this study, we found a decreasing trend in resistance rates and low resistance rates in P. aeruginosa from non-tertiary care hospitals compared with those from general hospitals, including tertiary care hospitals, in Korea. Our data provide valuable information for the selection of reliable empiric therapies for P. aeruginosa infections in non-tertiary care hospital patients, including outpatients. [Copyright &y& Elsevier]

Prion diseases are a group of neurodegenerative and fatal central nervous system disorders. The pathogenic mechanism involves the conversion of cellular prion protein (PrP C ) to an altered scrapie isoform (PrP Sc ), which accumulates in amyloid deposits in the brain. However, no therapeutic drugs have demonstrated efficacy in clinical trials. We previously reported that BMD42-29, a synthetic compound discovered in silico , is a novel anti-prion compound that inhibits the conversion of PrP C to protease K (PK)-resistant PrP Sc fragments (PrP res ). In the present study, 14 derivatives of BMD42-29 were obtained from BMD42-29 by modifying in the side chain by in silico feedback, with the aim to determine whether they improve anti-prion activity. These derivatives were assessed in a PrP Sc -infected cell model and some derivatives were further tested using real timequaking induced conversion (RT-QuIC). Among them, BMD42-2910 showed high anti-prion activity at low concentrations in vitro and also no toxic effects in a mouse model. Interestingly, abundant PrP res was reduced in brains of mice infected with prion strain when treated with BMD42- 2910, and the mice survived longer than control mice and even that treated with BMD42-29. Finally, high binding affinity was predicted in the virtual binding sites (Asn159, Gln 160, Lys194, and Glu196) when PrP C was combined with BMD-42-2910. Our findings showed that BMD42-2910 sufficiently reduces PrP res generation in vitro and in vivo and may be a promising novel anti-prion compound.