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Objective Pulmonary arteriovenous malformation (PAVM) is a rare pulmonary disease. Although most patients with PAVMs are asymptomatic, cerebral complications associated with PAVMs are often fatal. This study aimed to evaluate the risk factors for cerebral complications in patients with PAVMs. Methods We retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital. Results Fifty-five patients diagnosed with PAVMs were enrolled in this study. Most patients were female (89.1%), and the median age was 53 years. Thirty patients (54.5%) had incidentally detected PAVMs without symptoms. Twenty-four patients (43.7%) with PAVMs were treated with embolotherapy or surgery. Thirteen patients (23.6%) had cerebral complications. There was no significant difference in the development of cerebral complications according to treatment; however, older age (≥ 65 years) was associated with the development of new cerebral complications in untreated patients with PAVMs (odds ratio, 17.09; 95% confidence interval, 1.16–250.31; P = 0.038). Conclusion Older age (≥ 65 years) was a risk factor for the development of cerebral complications in patients with PAVMs; therefore, treatment should be considered in older patients with PAVMs.

Introduction We aimed to evaluate the association between the phase angle and muscle mass, muscle strength, physical performance tests, quality-of-life scales, mood scales, or patient and hospitalization-free survival rates in hemodialysis (HD) patients. Methods We included 83 HD patients. The patients were divided into tertiles based on phase angle value. The phase angle was measured using a bioimpedance analysis machine. Thigh muscle area per height squared (TMA/Ht2), handgrip strength (HGS), nutritional indicators, physical performance, quality-of-life, depression or anxiety status, and the presence of hospitalization or death regardless of cause were evaluated. Results In our study, no significant differences were observed in the serum albumin level and body mass index according to tertiles of phase angle. The phase angle tertiles were associated with TMA/Ht2 and HGS. The phase angle was also associated with physical performance measurements and depression or anxiety status. Subgroup analyses according to sex, age, and diabetes mellitus showed similar trends to those of the total cohort. Furthermore, the hospitalization-free survival rate and patient survival rate were favorable in patients with high values for the phase angle. Conclusion The present study demonstrated that the phase angle is associated with muscle mass, strength, physical performance, quality-of-life scale, and hospitalization-free survival in maintenance HD patients.

Perception-action coordination (also known as sensorimotor synchronization, SMS) is often studied by analyzing motor coordination with auditory rhythms. The current study assesses phasing—a compositional technique in which two people tap the same rhythm at varying phases by adjusting tempi—to explore how SMS is impacted by individual and situational factors. After practice trials, participants engaged in the experimental phasing task with a metronome at tempi ranging from 80–140 beats per minute (bpm). Multidimensional recurrence quantification analysis (MdRQA) was used to compare nonlinear dynamics of phasing performance. Varying coupling patterns emerged and were significantly predicted by tempo and linguistic experience. Participants who successfully phased replicated findings from an original case study, demonstrating stable tapping patterns near in-phase and antiphase, while those unsuccessful at phasing showed weaker attraction to in-phase and antiphase.

Background Several studies suggest improved outcomes for patients with kidney disease who consult a nephrologist. However, it remains undetermined whether a consultation with a nephrologist is related to a survival benefit after starting continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI). Methods Data from 2,397 patients who started CRRT due to severe AKI at Seoul National University Hospital, Korea between 2010 and 2020 were retrospectively collected. The patients were divided into two groups according to whether they underwent a nephrology consultation regarding the initiation and maintenance of CRRT. The Cox proportional hazards model was used to calculate the hazard ratio (HR) of mortality during admission to the intensive care unit after adjusting for multiple variables. Results A total of 2,153 patients (89.8%) were referred to nephrologists when starting CRRT. The patients who underwent a nephrology consultation had a lower mortality rate than those who did not have a consultation (HR = 0.47 [0.40–0.56]; P < 0.001). Subsequently, patients who had nephrology consultations were divided into two groups (i.e., early and late) according to the timing of the consultation. Both patients with early and late consultation had lower mortality rates than patients without consultations, with HRs of 0.45 (0.37–0.54) and 0.51 (0.42–0.61), respectively. Conclusions Consultation with a nephrologist may contribute to a survival benefit after starting CRRT for AKI.

Background The available data are not sufficient to understand the clinical impact of statin intensity in elderly patients who undergo percutaneous coronary intervention (PCI) due to acute myocardial infarction (AMI). Methods Using the COREA-AMI registry, we sought to compare the clinical impact of high- versus low-to-moderate-intensity statin in younger ( Results In younger patients, high-intensity statin showed the better clinical outcomes than low-to-moderate-intensity statin (TVF: 79 [5.4%] vs. 329 [6.8%], adjusted hazard ratio [aHR] 0.76; 95% confidence interval [CI] 0.59–0.99; P = 0.038). However, in elderly patients, the incidence rates of the adverse clinical outcomes were similar between two statin-intensity groups (TVF: 38 [11.4%] vs. 131 [10.6%], aHR 1.1; 95% CI 0.76–1.59; P = 0.63). Conclusions In this AMI cohort underwent PCI, high-intensity statin showed the better 1-year clinical outcomes than low-to-moderate-intensity statin in younger patients. Meanwhile, the incidence rates of adverse clinical events between high- and low-to-moderate-intensity statin were not statistically different in elderly patients. Further randomized study with large elderly population is warranted.

We evaluated the diagnostic accuracy of two newly developed, point-of-care, rapid antigen tests (RATs) for detecting SARS-CoV-2, the AFIAS COVID-19 Ag and the ichromaTM COVID-19 Ag, and investigated antigen kinetics. A total of 200 serially collected nasopharyngeal (NP) specimens from 38 COVID-19 patients and 122 specimens from negative controls were analyzed. Diagnostic sensitivity and specificity were assessed in comparison to molecular test results and subdivided according to targeted genes (E, RdRP, and N) and days post-symptom onset (PSO). For the kinetics evaluation, cut-off-indices from serial NP specimens were used according to the number of days PSO. Both RATs showed sensitivity of 91.3‒100% for specimens with cycle threshold (Ct) < 25. The specificity of AFIAS was 98.7‒98.9% and that of ichromaTM was 100.0%. The kappa values of AFIAS and ichromaTM for the molecular testing of specimens with Ct < 25 (RdRP) were 0.97 and 1.00, respectively. The sensitivity of AFIAS and ichromaTM for all genes was lower for specimens collected at 8‒14 PSO than for those collected before 7-days PSO. The kinetics profiles showed that antigen levels gradually decreased from ≤ 7-days PSO to > 22-days PSO. Both RATs showed excellent specificity and acceptable sensitivity for NP specimens with higher viral loads and for specimens collected within 7-days PSO. Hence, they have the potential to become useful tools for the early detection of SARS-CoV-2. However, because of concerns about false negativity, RATs should be used in conjunction with molecular tests.

During the coronavirus disease (COVID-19) pandemic, social distancing was effective in controlling disease spread across South Korea. The impact of national social distancing on the spread of common respiratory virus infections has rarely been investigated. We evaluated the weekly proportion of negative respiratory virus polymerase chain reaction (PCR) test results and weekly positive rates of each respiratory virus during the social distancing period (10th–41st weeks of 2020) and the corresponding period in different years, utilizing the national respiratory virus surveillance dataset reported by the Korean Center for Disease Control and Prevention. The proportions of negative respiratory virus PCR test results increased up to 87.8% and 86.1% during level 3 and level 2 of the social distancing period, respectively. The higher the level of social distancing, the higher the proportion of negative respiratory virus PCR test results. During the social distancing period, the mean weekly positive rates for parainfluenza virus, influenza virus, human coronavirus, and human metapneumovirus were significantly lower than those during the same period in 2015–2019 (0.1% vs. 9.3%, P P P P P P

Endemic human coronaviruses (HCoVs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are members of the family Coronaviridae. Comparing the findings of the infections caused by these viruses would help reveal the novel characteristics of SARS-CoV-2 and provide insight into the unique pathogenesis of SARS-CoV-2 infection. This study aimed to compare the clinical and radiological characteristics of SARS-CoV-2 and endemic HCoVs infection in adult hospitalized patients with community-acquired pneumonia (CAP). This study was performed at a university-affiliated tertiary hospital in the Republic of Korea, between January 1, 2015, and July 31, 2020. A total of 109 consecutive patients who were over 18 years of age with confirmed SARS-CoV-2 and endemic HCoVs were enrolled. Finally, 19 patients with SARS-CoV-2 CAP were compared to 40 patients with endemic HCoV CAP. Flu-like symptoms such as cough, sore throat, headache, myalgia, and prolonged fever were more common in SARS-CoV-2 CAP, whereas clinical findings suggestive of bacterial pneumonia such as dyspnea, leukocytosis with left shift, and increased C-reactive protein were more common in endemic HCoV CAP. Bilateral peripherally distributed ground-glass opacities (GGOs) were typical radiologic findings in SARS-CoV-2 CAP, whereas mixed patterns of GGOs, consolidations, micronodules, and pleural effusion were observed in endemic HCoV CAP. Coinfection was not observed in patients with SARS-CoV-2 CAP, but was observed in more than half of the patients with endemic HCoV CAP. There were distinctive differences in the clinical and radiologic findings between SARS-CoV-2 and endemic HCoV CAP. Further investigations are required to elucidate the mechanism underlying this difference. Follow-up observations are needed to determine if the presentation of SARS-CoV-2 CAP changes with repeated infection.

Objective Pneumocystis jirovecii pneumonia (PCP) is a fatal respiratory infection, mostly associated with immunocompromised conditions. Several reports have described PCP development in patients who were not immunocompromised, but the clinical course and prognosis of PCP are not well understood. We compared the clinical characteristics and prognoses between patients with and without immunocompromised conditions who developed PCP. Methods We retrospectively analyzed patients who had been treated for PCP from three hospitals. We defined immunocompromised (IC) status as following: human immunodeficiency virus (HIV) infection; hematological malignancy; solid organ tumor under chemotherapy; rheumatic disease; medication with immunosuppressive agents. Patients without immunocompromised status were defined as being non-immunocompromised (non-IC). Results The IC and non-IC groups comprised 173 and 14 patients. The median ages were 62.0 and 74.0 years in the IC and the non-IC group, respectively. The median interval between admission and anti-PCP treatment was significantly longer for patients in the non-IC group than that for patients in the IC group (7 vs. 2 days). The in-hospital mortality rates were significantly higher for patients in the non-IC group than that for patients in the IC group (71.4% vs. 43.9%; P = 0.047). A longer interval between admission and anti-PCP therapy was associated with increased 90-day mortality rate in patients with PCP (hazard ratio, 1.082; 95% confidence interval, 1.015–1.153; P = 0.016). Conclusions Patients with PCP with no predisposing illnesses were older and had higher mortality rates than IC patients with PCP. Delayed anti-PCP treatment was associated with increased 90-day mortality.

As adult height is linked to various health outcomes, further investigation of its causal effects on kidney function later in life is warranted. This study involved a cross-sectional observational analysis and summary-level Mendelian randomization (MR) analysis. First, the observational association between height and estimated GFR determined by creatinine (eGFRcreatinine) or cystatin C (eGFRcystatinC) was investigated in 467,182 individuals aged 40–69 using UK Biobank. Second, the genetic instrument for adult height, as reported by the GIANT consortium, was implemented, and summary-level MR of eGFRcreatinine and CKDcreatinine in a CKDGen genome-wide association study was performed (N = 567,460), with multivariable MR being adjusted for the effects of genetic predisposition on body mass index. To replicate the findings, additional two-sample MR using the summary statistics of eGFRcystatinC and CKDcystatinC in UK Biobank was performed (N = 321,405). In observational analysis, adult height was inversely associated with both eGFRcreatinine (per 1 SD, adjusted beta -1.039, standard error 0.129, P < 0.001) and eGFRcystatinC (adjusted beta -1.769, standard error 0.161, P < 0.001) in a multivariable model adjusted for clinicodemographic, anthropometric, metabolic, and social factors. Moreover, multivariable summary-level MR showed that a taller genetically predicted adult height was causally linked to a lower log-eGFRcreatinine (adjusted beta -0.007, standard error 0.001, P < 0.001) and a higher risk of CKDcreatinine (adjusted beta 0.083, standard error 0.019, P < 0.001). Other pleiotropy-robust sensitivity MR analysis results supported the findings. In addition, similar results were obtained by two-sample MR of eGFRcystatinC (adjusted beta -1.303, standard error 0.140, P < 0.001) and CKDcystatinC (adjusted beta 0.153, standard error 0.025, P < 0.001) in UK Biobank. In conclusion, the results of this study suggest that a taller adult height is causally linked to worse kidney function in middle-aged to elderly individuals, independent of the effect of body mass index.

Smoking, metabolic syndrome (MetS), and major adverse cardiovascular events (MACEs) are important global health problems. We aimed to investigate the association between smoking, alteration in MetS status, and the consequent risk of MACE. We performed a nationwide observational cohort study based on the claims database of Korea. We included people with ≥ 3 national health screenings from 2009 to 2013. Total 6,099,717 people, including 3,576,236 nonsmokers, 862,210 ex-smokers, 949,586 light-to-moderate smokers, and 711,685 heavy smokers, at the first health screening, were investigated. First, we performed a logistic regression analysis using smoking status at the first screening as the exposure variable and MetS development or recovery as the outcome variable. Second, we performed a Poisson regression using smoking status at the third screening as the exposure variable and the outcome was risk of incident MACEs. Among those previously free from MetS (N = 4,889,493), 347,678 people developed MetS, and among those who had previous MetS (N = 1,210,224), 347,627 people recovered from MetS. Smoking was related to a higher risk of MetS development [for heavy smokers: adjusted OR 1.71 (1.69 to 1.73)] and a lower probability of MetS recovery [for heavy smokers: adjusted OR 0.68 (0.67 to 0.69)]. Elevated triglycerides was the MetS component with the most prominent association with smoking. The risk for incident MACEs (78,640 events during a median follow-up of 4.28 years) was the highest for heavy smokers, followed in order by light-to-moderate, ex-smokers and nonsmokers, for every MetS status. Therefore, smoking may promote MetS or even hinder recovery from MetS. Smoking cessation should be emphasized to reduce MACE risk even for those without MetS.

Saussurea polylepisNakai is an herbaceous perennial endemic to Korea and is highly restricted to several continental islands in the southwestern part of the Korean Peninsula. Given its very narrow geographical distribution, it is more vulnerable to anthropogenic activities and global climate changes than more widely distributed species. Despite the need for comprehensive genetic information for conservation and management, no such population genetic studies ofS.polylepishave been conducted. In this study, genetic diversity and population structure were evaluated for 97 individuals from 5 populations (Gwanmaedo, Gageodo, Hongdo, Heusando, and Uido) using 19 polymorphic microsatellites. The populations were separated by a distance of 20–90 km. We found moderate levels of genetic diversity inS.polylepis(Ho= 0.42,He= 0.43). This may be due to long lifespans, outcrossing, and gene flow, despite its narrow range. High levels of gene flow (Nm= 1.76, meanFst= 0.09), especially from wind-dispersed seeds, would contribute to low levels of genetic differentiation among populations. However, the small population size and reduced number of individuals in the reproductive phase ofS.polylepiscan be a major threat leading to inbreeding depression and genetic diversity loss. Bayesian cluster analysis revealed three significant structures at K = 3, consistent with DAPC and UPGMA. It is thought that sea level rise after the last glacial maximum may have acted as a geographical barrier, limiting the gene flow that would lead to distinct population structures. We proposed the Heuksando population, which is the largest island inhabited byS.polylepis, as a source population because of its large population size and high genetic diversity. Four management units (Gwanmaedo, Gageodo, Hongdo-Heuksando, and Uido) were suggested for conservation considering population size, genetic diversity, population structure, unique alleles, and geographical location (e.g., proximity).

Due to substantial population decline, the Korean orchid P. scolopendrifolia is considered endangered and highly threatened. Like many endangered species, it is vulnerable to biological and anthropogenic threats that can lead to the loss of genetic diversity and, ultimately, extinction. Therefore, the assessment of genetic diversity and population genetic structure is imperative for conservation. In this study, we newly developed 15 polymorphic microsatellite markers. Analyses of genetic diversity and population genetic structure that included 182 samples from 11 populations were conducted using microsatellite markers and four noncoding regions of chloroplast DNA. Our study revealed a relatively low level of genetic diversity (Ho = 0.529, He = 0.356), albeit harboring with private alleles based on microsatellite genotyping data, and high haplotype diversities based on chloroplast DNA sequences data. The results of STRUCTURE and PCoA based on microsatellite genotyping data showed population differentiations. An AMOVA based on chloroplast DNA sequence data further corroborated these conclusions, indicating about 70% of variations found among populations. Low genetic diversity and divergence among the population might have been caused by factors, such as asexual reproduction, demographic events (bottleneck and population expansion), geographic isolation, and low gene flow. The development and implication of conservation strategies and management of P. scolopendrifolia are proposed based on these results.

BackgroundCoronavirus disease 2019 (COVID-19) is an emerging threat worldwide. This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays.MethodsA total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI™ Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA).ResultsWith both assays, IgM and IgG rapidly increased after 7 days post symptom onset (PSO). IgM antibody levels reached a peak at 15-35 d PSO and gradually decreased. IgG levels gradually increased and remained at similar levels after 22-35 d. The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI™ Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results.ConclusionsThe antibody kinetics against SARS-CoV-2 are similar to common findings of acute viral infectious diseases. Antibody testing is useful for ruling out SARS-CoV-2 infection after 14 d PSO, detecting past infection, and epidemiologic surveys.

Background A number of studies have been conducted on the relationship between the distribution of mosquito abundance and meteorological variables. However, few studies have specifically provided specific ranges of temperatures for estimating the maximum abundance of mosquitoes as an empirical basis for climatic dynamics for estimating mosquito-borne infectious disease risks.Methods Adult mosquitoes were collected for three consecutive nights/week using Mosquito Magnet® Independence® model traps during 2018 and 2019 at US Army Garrison (USAG) Humphreys, Pyeongtaek, Gyeonggi Province, Republic of Korea (ROK). An estimate of daily mean temperatures (provided by the Korea Meteorological Administration) were distributed at the maximum abundance for selected species of mosquitoes using daily mosquito collection data after controlling for mosquito ecological cycles and environmental factors.Results Using the Monte-Carlo simulation, the overall mosquito population abundance peaked at 22.7℃ (2.5th−-97.5th : 21.7℃–23.8 ℃). Aedes albopictus, vector of Zika, chikungunya, dengue fever and other viruses, abundance peaked at 24.6℃ (2.5th − 97.5th, 22.3℃–25.6℃), while Japanese encephalitis virus (JEV) vectors, e.g., Culex tritaeniorhynchus and Culex pipiens, peaked at 24.3℃ (2.5th − 97.5th : 21.9℃–26.3℃) and 22.6℃ (2.5th − 97.5th : 21.9℃–25.2℃), respectively. Members of the Anopheles Hyrcanus Group, some of which are vivax malaria vectors in the ROK, abundance peaked at 22.4℃ (2.5th − 97.5th : 21.5℃–23.8℃).Conclusion The empirical mean temperature ranges for maximum abundance were determined for each mosquito species collected at USAG Humphreys. These data contributed to the identification of relative mosquito abundance patterns for estimating mosquito-borne disease risks and developing and implementing disease prevention practices.

Objectives Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. Methods We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. Results Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. Conclusions The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.

Few large-scale studies have been conducted to show the joint effects of mortality associated with physical activity and sedentarism. Therefore, we examined the relationship between all-cause mortality and behavioral patterns among adults in the United States. Data of 17,730 non-institutionalized US civilians aged ≥20 years were extracted from the 2007–2014 National Health and Nutrition Examination Survey. We set the criteria for metabolic equivalents as 600 according to the WHO guideline, and sedentary time as 300 min/day according to the median. The Cox proportional hazards model was adjusted for demographic and lifestyle characteristics. During the 58.54±28.18 months follow-up, all-cause mortality rate was 4% and heart-related and cancer mortality rate was 1%. Participants in the high metabolic equivalents and low sedentary time group had a lower risk of all-cause (hazard ratio = 0.41, 95% confidence interval = 0.34–0.50), cardiovascular (hazard ratio = 0.36; 95% confidence interval = 0.23–0.55), and cancer (hazard ratio = 0.55; 95% confidence interval = 0.37–0.83) mortality, compared to those in the low metabolic equivalents and high sedentary time group. Sufficient physical activity and less sedentary behavior reduce all-cause and cause-specific mortality in adults in the United States, especially cardiovascular mortality among the elderly. Additional nationwide policies to improve behavioral patterns among adults need to be implemented in the United States.

BackgroundThe prognostic role of BDNF val66met polymorphism on long-term cardiac outcomes in acute coronary syndrome (ACS) has been unclear. Environmental factors may modify the association, but these have not been investigated to date. This study aimed to investigate the potential interactive effects of BDNF val66met polymorphism and personality traits, one of the main environmental prognostic factors of ACS, on major adverse cardiac events (MACEs) in patients with ACS.MethodsA total of 611 patients with recent ACS were recruited at a university hospital in Korea. Baseline evaluations from 2007 to 2012 assessed BDNF val66met polymorphism and personality using the Big Five Inventory, which yielded two personality clusters (resilient and vulnerable) and five dimensions (extraversion, agreeableness, conscientiousness, neuroticism, and openness). Over a 5~12 year follow-up after the index ACS, times to MACE were investigated using Cox regression models after adjustment for a range of covariates.ResultsThe BDNF val66met polymorphism modified the associations between vulnerable personality type and worse long-term cardiac outcomes in ACS patients with significant interaction terms, in that the associations were statistically significant in the presence met allele. Similar findings were observed for the individual personality dimensions of agreeableness and neuroticism.ConclusionsGene (BDNF val66met polymorphism) x environment (personality traits) interactions on long-term cardiac outcomes were found in ACS.

Background Glomerular hyperfiltration may be a clinical phenotype of endothelial dysfunction. Endothelial dysfunction may cause vascular dementia through the deterioration of cerebral blood flow. We aimed to identify the risk of dementia in people with glomerular hyperfiltration. Methods Using the Korean National Health Information Database, we included subjects aged ≥45 years who underwent national health screening examinations between 2012 and 2015 and who had no previous history of end-stage renal disease or dementia (n = 2,244,582). The primary exposure was glomerular hyperfiltration. We divided the subjects into groups by sex and five-year age intervals and categorized each group into 8 intervals according to estimated glomerular filtration (eGFR). The subjects with an eGFR ≥95th percentile in each group were defined as the hyperfiltration group. The outcomes were development of all types of dementia, Alzheimer's dementia and vascular dementia. Multivariable Cox proportional hazards models were used to analyze the hazard ratios (HRs) for outcomes. Results The Hyperfiltration group showed a higher risk for the development of all types of dementia [adjusted HR 1.09 (95% CI, 1.03-1.15)] and vascular dementia [adjusted HR 1.33 (95% CI, 1.14-1.55)] than the reference group. However, the association between hyperfiltration and Alzheimer's dementia was not statistically significant. Conclusions Glomerular hyperfiltration may be associated with dementia. In this respect, subjects with glomerular hyperfiltration should be monitored more closely for signs and symptoms of dementia.

Objective This study aimed to evaluate hypersensitivity reactions to anti-tuberculosis (TB) drugs. Methods We retrospectively compared the clinical manifestations and treatment outcomes of single and multiple drug hypersensitivity reactions (DHRs). Results Twenty-eight patients were diagnosed with anti-TB DHRs using oral drug provocation tests. Of these 28 patients, 17 patients (60.7%) had DHRs to a single drug and 11 (39.3%) had multiple DHRs. The median age of patients was 57.5 years (interquartile range [IQR], 39.2–73.2). Of the total patients, 18 patients (64.3%) were men. The median number of anti-TB drugs causing multiple DHRs was 2.0 (IQR 2.0–3.0). Rifampin was the most common drug that caused DHRs in both the single and multiple DHR groups (n = 8 [47.1%] and n = 9 [52.9%], respectively). The treatment success rate was lower in the multiple DHR group than in the single DHR group; however, the difference was not statistically significant (81.8% vs. 94.1%; P = 0.543). Conclusions Multiple anti-TB DHRs were common in all patients who experienced DHRs, and rifampin was the most common causative drug. The treatment outcomes appeared to be poorer in patients with multiple DHRs than in those with single DHRs.

This study aimed to investigate the relationship between serum zinc level and hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). A cross-sectional study was conducted using nationally representative samples from the Korea National Health and Nutrition Examination Survey 2010. Significant hepatic fibrosis was defined as Fibrosis-4 (FIB-4) index>1.3. Zinc level was measured using inductively coupled plasma mass spectrometry. Univariable and multivariable logistic regression analyses were performed to assess risk factors for significant hepatic fibrosis in patients with NAFLD. A total of 300 patients with NAFLD were analyzed in this study. The mean serum zinc level was 139.8±29.9 μg/dL. FIB-4 index was significantly increased as the serum zinc level decreased (Adjusted correlation coefficient = -0.177, p = 0.003). Significant liver fibrosis was observed in 62 patients (21%). The multivariable analysis showed that significant liver fibrosis in NAFLD was associated with diabetes mellitus (odds ratio [OR], 3.25; 95% confidence interval [CI], 1.71–6.19; p

Phedimus takesimensis (Ulleungdo flat-leaved stonecrop) is endemic to Ulleung and Dokdo Islands off the east coast of the Korean Peninsula. It was suggested that P. takesimensis originated via anagenetic speciation from the continental progenitor species P. kamtchaticus or P. aizoon. However, little is known of the phylogenetic relationships and population genetic structure among species of Phedimus in the Korean Peninsula and Ulleung/Dokdo Islands. We inferred the phylogenetic relationships among congeneric species in Korea based on nuclear ribosomal DNA internal transcribed spacer and chloroplast noncoding regions. We also sampled extensively for P. takesimensis on Ulleung Island and the continental species, P. kamtschaticus and P. aizoon, to assess the genetic consequences of anagenetic speciation. We found (1) the monophyly of P. takesimensis, (2) no apparent reduction in genetic diversity in anagenetically derived P. takesimensis compared to the continental progenitor species, (3) apparent population genetic structuring of P. takesimensis, and (4) two separate colonization events for the origin of the Dokdo Island population. This study contributes to our understanding of the genetic consequences of anagenetic speciation on Ulleung Island.

The association of lipid parameters with cardiovascular outcomes and the impact of kidney function on this association have not been thoroughly evaluated in chronic kidney disease (CKD) patients with diabetes. We reviewed the National Health Insurance Database of Korea, containing the data of 10,505,818 subjects who received routine check-ups in 2009. We analyzed the association of lipid profile parameters with major adverse cardiovascular events (MACEs) risk and all-cause mortality in a nationally representative cohort of 51,757 lipid-lowering medication-naïve patients who had CKD and diabetes. Advanced CKD patients with eGFR

Artificial selection has been demonstrated to have a rapid and significant effect on the phenotype and genome of an organism. However, most previous studies on artificial selection have focused solely on genomic sequences modified by artificial selection or genomic sequences associated with a specific trait. In this study, we generated whole genome sequencing data of 126 cattle under artificial selection, and 24,973,862 single nucleotide variants to investigate the relationship among artificial selection, genomic sequences and trait. Using runs of homozygosity detected by the variants, we showed increase of inbreeding for decades, and at the same time demonstrated a little influence of recent inbreeding on body weight. Also, we could identify ~0.2 Mb runs of homozygosity segment which may be created by recent artificial selection. This approach may aid in development of genetic markers directly influenced by artificial selection, and provide insight into the process of artificial selection.

Objectives Statins, which are lipid-lowering agents, have anti-inflammatory and immunomodulatory properties that may affect the occurrence of various infectious diseases. We assessed whether statins increase the risk of herpes zoster (HZ) with propensity score-matching. Methods The study was based on the National Health Insurance database and its subset database of the “medical check-up” population of South Korea. These cohorts consist of about one million and 570,000 people, respectively, representative of the entire population of South Korea. We identified 103,930 statin users and 430,685 non-statin users. After propensity score-matching, 25,726 statin users and the same number of non-statin users were finally analyzed. The development of HZ was monitored in these matched pairs over the 11 years from 2003 to 2013. Results Statin users had a significantly higher risk of HZ than non-statin users: hazard ratio (HR) 1.25 (95% CI, 1.15 to 1.37) (p < .0001). The risk of HZ associated with statins was especially high in the elderly: HR 1.39 (95% CI, 1.12 to 1.73) in the over 70-year-olds (p = 0.003) and HR 1.18 (95% CI, 1.00 to 1.39) in the 60-to-69-year-olds (p = 0.056). Furthermore, there was a significant p for trend in terms of cumulative dose effect between the risk of HZ and the duration of statin use (p < .0001). Conclusions These epidemiologic findings provide strong evidence for an association between HZ and statin use, and suggest that unnecessary statins should be avoided.

The immunosuppressive drug tacrolimus has the short-term effect of reducing proteinuria in patients with immunoglobulin A nephropathy (IgAN). Our study investigated the effects on proteinuria and kidney function after discontinuation of tacrolimus.Patients with biopsy-proven IgAN were included in the study and randomly divided into two treatment groups. There was a corresponding control group for each treatment group. The first group included patients treated with tacrolimus (Tac vs non-Tac group) and the second group included patients with a renin angiotensin system blocker (RASi vs non-RASi group). The Tac group received treatment for up to 16 weeks, with the administration of tacrolimus being ceased at the final visit (trial phase). We tracked the patients at 12, 24, 52, and 240 weeks (observational phase). The primary outcomes examined were the percentage change (from the trial phase to the observational phase) of time-averaged proteinuria (TA-proteinuria; g/g creatinine [cr]) and the estimated glomerular filtration rate (eGFR). Time-averaged proteinuria was defined as the average of urine protein to creatinine ratio (UPCR), measured every 3 months during both the trial and observational phases of the study.A significant reduction in UPCR was observed in the Tac group compared to non-Tac group at the 4 and 8 week visits during the trial phase (p = 0.023 and p = 0.003, respectively). However, the difference between the Tac group and non-Tac group was not evident in the other review periods, estimated by linear mixed effect model. The percentage change in TA-proteinuria was greater in the Tac group than that in the corresponding control group (116 ± 96% vs. 63 ± 239%, p = 0.004). Therefore, during the observational phase, TA-proteinuria was not significantly different between the Tac group and the non-Tac group (1.150 ± 0.733 g/g cr vs. 1.455 ± 2.017 g/g cr, p = 0.775). The levels of eGFR throughout the observational phase were not significantly different between the two groups. Furthermore, the mean rate of eGFR change throughout both phases of the study was -6.4 ± 5.9 mL/min/1.73 m2/year in the non-Tac group and -5.4 ± 7.9 mL/min/1.73 m2/year in the Tac group (p = 0.988).The anti-proteinuric effect of tacrolimus was promptly reversed 3 months after discontinuing the drug. The use of tacrolimus for a short period of time for patients with IgAN temporarily reduces proteinuria, but the data showed no long-term efficacy regarding proteinuria reduction and improvement of renal function.

Current influenza vaccines do not provide broad cross-protection. Here, we report that intranasal vaccination with virus-like particles containing the highly conserved multiple ectodomains of matrix protein 2 (M2e5x VLP) of influenza virus induces broad cross-protection by M2-specific humoral and cellular immune responses. M2e5x VLP intranasal vaccination prevented severe weight loss, attenuated inflammatory cytokines and cellular infiltrates, and lowered viral loads, and induced germinal center phenotypic B and plasma cells. In addition, depletion studies demonstrate the protective roles of CD4 and CD8 T cells induced by M2e5x VLP intranasal vaccination. Thus, this study provides evidence that mucosal delivery of M2e5x VLP vaccine provides cross-protection by inducing humoral and cellular immune responses.

Background and aims Laterally spreading colorectal tumors (LSTs) are divided into four subtypes, including homogenous (HG), nodular mixed (NM), flat elevated (FE), and pseudo-depressed (PD), based on their different endoscopic morphologies. The aim of this study was to investigate the clinicopathological significance of LST subtypes and their association with advanced histology. Methods We investigated the medical records of consecutive patients with LST who initially underwent endoscopic resection at five university hospitals in Honam province of South Korea between January 2012 and December 2013. A total of 566LST lesions removed via endoscopic procedures were collected retrospectively for data analysis. Results The PD, FE, and NM subtypes were more common in the distal colon and the HG subtype in the proximal colon. The PD subtype had the biggest tumor size, followed by the NM subtype. The frequency of adenomatous pit pattern was significantly higher in the HG, NM, and FE subtypes than in the PD subtype. In contrast, the frequency of cancerous pit pattern was significantly higher in the PD subtype than in the other three subtypes. The rate of advanced histology (high-grade dysplasia or carcinoma) among the LSTs was 36.0%. The risk of advanced histology increased in the distal colon compared with the proximal colon. The PD subtype had the highest incidence of villous component, advanced histology,submucosal invasion, and postprocedure perforation among the four subtypes. The distal colon as tumor site, larger tumor size, PD subtype, and villous component were associated with a statistically significant increased risk of advanced histology. Conclusion Our results indicate that the location, size, endoscopic subtype, and histologic component of the LSTs are associated with an increased risk of advanced histology. Therefore, these clinicopathological parameters may be useful in selecting therapeutic strategies in the clinical setting.

Periodontitis is an infectious disease that is associated with microorganisms that colonize the tooth surface. Clinically, periodontal condition stability reflects dynamic equilibrium between bacterial challenge and host response. Therefore, periodontal pathogen assessment can assist in the early detection of periodontitis. Here we developed a grading system called the periodontal pathogen index (PPI) by analyzing the copy numbers of multiple pathogens both in healthy and chronic periodontitis patients. We collected 170 mouthwash samples (64 periodontally healthy controls and 106 chronic periodontitis patients) and analyzed the salivary 16S rRNA levels of nine pathogens using multiplex, quantitative real-time polymerase chain reaction. Except for Aggregatibacter actinomycetemcomitans, copy numbers of all pathogens were significantly higher in chronic periodontitis patients. We classified the samples based on optimal cut-off values with maximum sensitivity and specificity from receiver operating characteristic curve analyses (AUC = 0.91, 95% CI: 0.87-0.96) into four categories of PPI: Healthy (1-40), Moderate (41-60), At Risk (61-80), and Severe (81-100). PPI scores were significantly higher in all chronic periodontitis patients than in the controls (odds ratio: 31.7, 95% CI: 13.41-61.61) and were associated with age, scaling as well as clinical characteristics including clinical attachment level and plaque index. Our PPI grading system can be clinically useful for the early assessment of pathogenic bacterial burden and follow-up monitoring after periodontitis treatment.

It remains inconclusive whether hyperuricemia is a true risk factor for kidney graft failure. In the current study, we investigated the association of hyperuricemia and graft outcome. We performed a multi-center cohort study that included 2620 kidney transplant recipients. The patients were classified as either normouricemic or hyperuricemic at 3 months after transplantation. Hyperuricemia was defined as a serum uric acid level ≥ 7.0 mg/dL in males or ≥ 6.0 mg/dL in females or based on the use of urate-lowering medications. The two groups were compared before and after propensity score matching. A total of 657 (25.1%) patients were classified as hyperuricemic. The proportion of hyperuricemic patients increased over time, reaching 44.2% of the total cohort at 5 years after transplantation. Estimated glomerular filtration rate and donor type were independently associated with hyperuricemia. Hyperuricemia was associated with graft loss according to multiple Cox regression analysis before propensity score matching (hazard ratio [HR] = 1.56, 95% confidence interval [CI] = 1.14-2.13, P = 0.005) as well as after matching (HR = 1.65, 95% CI = 1.13-2.42, p = 0.010). Cox regression models using time-varying hyperuricemia or marginal structural models adjusted with time-varying eGFR also demonstrated significant hazards of hyperuricemia for graft loss. Cardiovascular events and recipient survival were not associated with hyperuricemia. Overall, hyperuricemia, especially early onset after transplantation, showed an increased risk for graft failure. Further studies are warranted to determine whether lowering serum uric acid levels would be beneficial to graft survival.

Background The immunosuppressive drug tacrolimus has the short-term effect of reducing proteinuria in patients with immunoglobulin A nephropathy (IgAN). Our study investigated the effects on proteinuria and kidney function after discontinuation of tacrolimus. Methods Patients with biopsy-proven IgAN were included in the study and randomly divided into two treatment groups. There was a corresponding control group for each treatment group. The first group included patients treated with tacrolimus (Tac vs non-Tac group) and the second group included patients with a renin angiotensin system blocker (RASi vs non-RASi group). The Tac group received treatment for up to 16 weeks, with the administration of tacrolimus being ceased at the final visit (trial phase). We tracked the patients at 12, 24, 52, and 240 weeks (observational phase). The primary outcomes examined were the percentage change (from the trial phase to the observational phase) of time-averaged proteinuria (TA-proteinuria; g/g creatinine [cr]) and the estimated glomerular filtration rate (eGFR). Time-averaged proteinuria was defined as the average of urine protein to creatinine ratio (UPCR), measured every 3 months during both the trial and observational phases of the study. Results A significant reduction in UPCR was observed in the Tac group compared to non-Tac group at the 4 and 8 week visits during the trial phase (p = 0.023 and p = 0.003, respectively). However, the difference between the Tac group and non-Tac group was not evident in the other review periods, estimated by linear mixed effect model. The percentage change in TA-proteinuria was greater in the Tac group than that in the corresponding control group (116 ± 96% vs. 63 ± 239%, p = 0.004). Therefore, during the observational phase, TA-proteinuria was not significantly different between the Tac group and the non-Tac group (1.150 ± 0.733 g/g cr vs. 1.455 ± 2.017 g/g cr, p = 0.775). The levels of eGFR throughout the observational phase were not significantly different between the two groups. Furthermore, the mean rate of eGFR change throughout both phases of the study was -6.4 ± 5.9 mL/min/1.73 m2/year in the non-Tac group and -5.4 ± 7.9 mL/min/1.73 m2/year in the Tac group (p = 0.988). Conclusion The anti-proteinuric effect of tacrolimus was promptly reversed 3 months after discontinuing the drug. The use of tacrolimus for a short period of time for patients with IgAN temporarily reduces proteinuria, but the data showed no long-term efficacy regarding proteinuria reduction and improvement of renal function.

Background Health-related quality of life (HRQoL) surveys are needed to evaluate regional and ethnic specificies. The aim of the present study was to evaluate the differences in HRQoL, frailty, and disability according to dialysis modality in the Korean population. Patients and methods We enrolled relatively stable maintenance dialysis patients. A total of 1,616 patients were recruited into our study. The demographic and laboratory data collected at enrollment included age, sex, comorbidities, frailty, disability, and HRQoL scales. Results A total of 1,250 and 366 participants underwent hemodialysis (HD) and peritoneal dialysis (PD), respectively. The numbers of participants with pre-frailty and frailty were 578 (46.2%) and 422 (33.8%) in HD patients, and 165 (45.1%) and 137 (37.4%) in PD patients, respectively (P = 0.349). Participants with a disability included 195 (15.6%) HD patients and 109 (29.8%) PD patients (P < 0.001). On multivariate analysis, the mean physical component scale (PCS) and mental component scale (MCS), symptom/problems, and sleep scores were higher in HD patients than in PD patients. Cox regression analyses showed that an increased PCS in both HD and PD patients was positively associated with patient survival and first hospitalization–free survival. An increased MCS in both HD and PD patients was positively associated with first hospitalization–free survival only. Conclusion There was no significant difference in frailty between patients treated with the two dialysis modalities; however, disability was more common in PD patients than in HD patients. The MCS and PCS were more favorable in HD patients than in PD patients. Symptom/problems, sleep, quality of social interaction, and social support were more favorable in HD patients than in PD patients; however, patient satisfaction and dialysis staff encouragement were more favorable in PD patients than in HD patients.

Background The optimal timing for initiating dialysis in end-stage renal disease (ESRD) is controversial, especially in the elderly. Methods 665 patients ≥65 years old who began dialysis from August 2008 to February 2015 were prospectively enrolled in the Clinical Research Center for End-Stage Renal Disease cohort study. Participants were divided into 2 groups based on the median estimated glomerular filtration rate at the initiation of dialysis. Propensity score matching (PSM) was used to compare the overall survival rate, cardiovascular events, Kidney Disease Quality of Life Short Form 36 (KDQOL-36) results, Karnofsky performance scale values, Beck’s depression inventory values, and subjective global assessments. Results The mean patient age was 72.0 years, and 61.7% of the patients were male. Overall, the cumulative survival rates were lower in the early initiation group, although the difference was not significant after PSM. Additionally, the survival rates of the 2 groups did not differ after adjusting for age, sex, Charlson comorbidity index and hemoglobin, serum albumin, serum calcium and phosphorus levels. Although the early initiation group showed a lower physical component summary score on the KDQOL-36 3 months after dialysis, the difference in scores was not significant 12 months after dialysis. Furthermore, the difference was not significant after PSM. The Karnofsky performance scale, Beck’s depression inventory, and subjective global assessments were not significantly different 3 and 12 months after dialysis initiation. Conclusions The timing of dialysis initiation is not associated with clinical outcomes in elderly patients with ESRD.

[This corrects the article DOI: 10.1371/journal.pone.0176786.].

To determine the origin and genetic consequences of anagenesis in Rubus takesimensis on Ulleung Island, Korea, we compared the genetic diversity and population structure of R. takesimensis with those of its continental progenitor R. crataegifolius. We broadly sampled a total of 315 accessions in 35 populations and sequenced five noncoding regions of chloroplast DNA. Rubus takesimensis emerged as nonmonophyletic and several geographically diverse continental populations were likely responsible for the origin of R. takesimensis; the majority of R. takesimensis accessions were sisters to the clade containing accessions of R. crataegifolius, primarily from the Korean peninsula, while rare accessions from three populations shared common ancestors with the ones from the southern part of the Korean peninsula, Jeju Island, and Japan. A few accessions from the Chusan population originated independently from the Korean peninsula. Of 129 haplotypes, 81 and 48 were found exclusively in R. crataegifolius and R. takesimensis, respectively. We found unusually high genetic diversity in two regions on Ulleung Island and no geographic population structure. For R. crataegifolius, two major haplotype groups were found; one for the northern mainland Korean peninsula, and the other for the southern Korean peninsula and the Japanese archipelago. Compared with populations of R. crataegifolius sampled from Japan, much higher haplotype diversity was found in populations from the Korean peninsula. The patterns of genetic consequences in R. takesimensis need to be verified for other endemic species based on chloroplast DNA and independent nuclear markers to synthesize emerging patterns of anagenetic speciation on Ulleung Island.

Despite the ability to induce a broad range of cross protection, M2e5x virus-like particles (VLPs) alone provide limited vaccine efficacy and confer low efficacy of protection against highly pathogenic avian influenza virus (HPAIV) infection in chickens. Avian influenza hemagglutinin (HA) has been a major antigenic target that enhances humoral immunity, but the efficacy of avian HA-based vaccines against HPAIV needs to be further improved. In this study, we evaluated the vaccine efficacy induced by combination of conserved tandem repeat M2e5x VLPs and HA VLPs against an avian influenza virus. We found that combinatorial vaccine elicited higher levels of reassortant H5N1 (rgH5N1) virus-specific IgG, IgG1, IgG2a and IgA antibody responses compared to M2e5x VLPs in sera and lungs of mice. Combinatorial VLPs vaccination induced higher levels of CD8+ T cell and germinal center B cell responses in lung and spleen compared to M2e5x VLPs. Combinatorial VLPs vaccination showed significantly reduced inflammatory responses and lung viral loads upon rgH5N1 virus challenge infection, resulting in less body weight loss compared to M2e5x VLPs alone. These results indicate that immune responses to both M2e and HA might provide a strategy of vaccination inducing enhanced protection against avian influenza virus.

Background Identification and understanding of the pathogens responsible for pleural infection is critical for appropriate antibiotic treatment. This study sought to determine the microbiological characteristics of pleural infection and to identify potential predictive factors associated with mortality. Methods In this retrospective study, we analyzed patient data from 421 cases of parapneumonic effusion. A total of 184 microorganisms were isolated from 164 patients, using two culture systems: a standard method and a method using pairs of aerobic and anaerobic blood culture bottles. Results The most frequently isolated microorganisms were streptococci (31.5%), followed by staphylococci (23.4%), gram-negative bacteria (18.5%) and anaerobes (10.3%). Streptococci were the main microorganisms found in standard culture (41.9%) and community-acquired infections (52.2%), and were susceptible to all antimicrobial agents in drug sensitivity testing. Staphylococci were the most frequently isolated pathogens in blood cultures (30.8%) and hospital-acquired infections (38.3%), and were primarily multidrug-resistant (61.8%). In multivariate analysis, the following were significant predictive factors for 30-day mortality among the total population: CURB-65 ≥ 2 (aOR 5.549, 95% CI 2.296–13.407, p

Purpose To investigate the association between blood 25-hydroxyvitamin D levels and pterygium. Methods Korean National Health and Nutrition Examination Survey 2008–2011 were used for the present epidemiologic study. A total of 19,178 participants aged ≥ 30 years were evaluated for blood 25-hydroxyvitamin D levels and performed ophthalmic slit lamp examinations. Pterygium was considered as a growth of fibrovascular tissue over the cornea. Results The average blood 25-hydroxyvitamin D levels were 18.6 ng/mL, and prevalence of pterygium was 6.5%. The odds of pterygium significantly increased across blood 25-hydroxyvitamin D quintiles after controlling sun exposure time as well as other confounders such as sex, age, smoking, diabetes, hypertension (P < 0.001). The odds ratios (OR) for pterygium was 1.51 (95% Confidence Interval[95%CI]; 1.19–1.92) in the highest blood vitamin D quintile. Stratified analysis by sex showed a positive association between blood 25-hydroxyvitamin D levels and pterygium in both men (quintile 5 versus 1, OR; 1.68, 95%CI; 1.19–2.37) and women (quintile 5 versus 1, OR; 1.37, 95% CI; 1.00–1.88). Conclusions Even after controlling sun light exposure time, we found a positive association between blood 25-hydroxyvitamin D levels and pterygium in a representative Korean population. The mechanism underlying this association is unknown.

Purpose Diabetic nephropathy is the leading cause of end stage renal disease. The number of kidney transplantation (KT) due to diabetic nephropathy is increasing and there is debate on glycemic control after KT. In this study, we used a multi-center database to determine the relationship between post-transplant glycemic control and the outcomes of KT in patients with diabetic nephropathy. Methods We conducted a retrospective chart review of kidney transplant recipients (KTRs) with diabetic nephropathy from three tertiary hospitals to analyze the association between post-transplant glycemic control and the clinical outcomes of graft failure, including patient death and biopsy-proven acute rejection (BPAR). We assessed time-averaged glucose level and hemoglobin A1c (HbA1c) for 36 months after KT. Results Among 3,538 KTRs, a total of 476 patients received kidney transplantation because of diabetic nephropathy. Mean time-averaged glucose and HbA1c levels were 147 ± 46 mg/dl and 7.7 ± 1.5%, respectively. Patients with diabetic nephropathy had poor graft and patient survival rate compared with non-diabetic nephropathy. Among KTRs with diabetic nephropathy, the highest quartile of time-averaged glucose was related to poor graft outcomes and the 3rd quartile of time-averaged HbA1c was associated with significantly better graft outcomes than the 1st, 2nd or 4th quartiles. There were no significant differences in the risk of BPAR across the 4 quartiles of glucose and HbA1c. Conclusions Strict glycemic control before KT might not be related to successful outcomes but poor glycemic control after KT is associated with poor graft outcomes. There was no significant relationship between pre- or post-transplant glycemic control and BPAR.

The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naïve mice. Also, M2e5x-immune complexes of virus-infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine.

Objective This study investigated the metabolic parameters of primary tumors and regional lymph nodes, as measured by pre-treatment F-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) to compare the prognostic value for the prediction of tumor recurrence. This study also identified the most powerful parameter in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy. Methods Fifty-six patients who were diagnosed with cervical cancer with pelvic and/or paraaortic lymph node metastasis were enrolled in this study. Metabolic parameters including the maximum standardized uptake value (SUVmax), the metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors and lymph nodes were measured by pre-treatment F-18 FDG PET/CT. Univariate and multivariate analyses for disease-free survival (DFS) were performed using the clinical and metabolic parameters. Results The metabolic parameters of the primary tumors were not associated with DFS. However, DFS was significantly longer in patients with low values of nodal metabolic parameters than in those with high values of nodal metabolic parameters. A univariate analysis revealed that nodal metabolic parameters (SUVmax, MTV and TLG), paraaortic lymph node metastasis, and post-treatment response correlated significantly with DFS. Among these parameters, nodal SUVmax (hazard ratio [HR], 4.158; 95% confidence interval [CI], 1.1–22.7; p = 0.041) and post-treatment response (HR, 7.162; 95% CI, 1.5–11.3; p = 0.007) were found to be determinants of DFS according to a multivariate analysis. Only nodal SUVmax was an independent pre-treatment prognostic factor for DFS, and the optimal cutoff for nodal SUVmax to predict progression was 4.7. Conclusion Nodal SUVmax according to pre-treatment F-18 FDG PET/CT may be a prognostic biomarker for the prediction of disease recurrence in patients with locally advanced cervical cancer.

The information about a marker compound's pharmacokinetics in herbal products including the characteristics of absorption, distribution, metabolism, excretion (ADME) is closely related to the efficacy/toxicity. Also dose range and administration route are critical factors to determine the ADME profiles. Since the supply of a sufficient amount of a marker compound in in vivo study is still difficult, pharmacokinetic investigations which overcome the limit of blood collection in mice are desirable. Thus, we have attempted to investigate concurrently the ADME and proposed metabolite identification of alpha-mangostin, a major constituent of mangosteen, Garcinia mangostana L, in mice with a wide dose range using an in vitro as well as in vivo automated micro-sampling system together. alpha-mangostin showed dose-proportional pharmacokinetics at intravenous doses of 5-20 mg/kg and oral doses of 10-100 mg/kg. The gastrointestinal absorption of a-mangostin was poor and the distribution of alpha-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. alpha-mangostin was extensively metabolized in the liver and intestine. With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated alpha-mangostins were tentatively identified. We suggest that these dose-independent pharmacokinetic characteristics of alpha-mangostin in mice provide an important basis for preclinical applications of alpha-mangostin as well as mangosteen. In addition, these experimental methods can be applied to evaluate the pharmacokinetics of natural products in mice.

Rickettsiae are associated with a diverse range of invertebrate hosts. Of these, mosquitoes could emerge as one of the most important vectors because of their ability to transmit significant numbers of pathogens and parasites throughout the world. Recent studies have implicated Anopheles gambiae as a potential vector of Rickettsia felis. Herein we report that a metagenome sequencing study identified rickettsial sequence reads in culicine mosquitoes from the Republic of Korea. The detected rickettsiae were characterized by a genus-specific quantitative real-time PCR assay and sequencing of rrs, gltA, 17kDa, ompB, and sca4 genes. Three novel rickettsial genotypes were detected (Rickettsia sp. A12.2646, Rickettsia sp. A12.2638 and Rickettsia sp. A12.3271), from Mansonia uniformis, Culex pipiens, and Aedes esoensis, respectively. The results underscore the need to determine the Rickettsia species diversity associated with mosquitoes, their evolution, distribution and pathogenic potential.

Emergence of tumor resistance to an anti-cancer therapy directed against a putative target raises several questions including: (1) do mutations in the target/pathway confer resistance? (2) Are these mutations pre-existing? (3) What is the relative fitness of cells with/without the mutation? We addressed these questions in patients with metastatic colorectal cancer (mCRC). We conducted an exhaustive review of published data to establish a median doubling time for CRCs and stained a cohort of CRCs to document mitotic indices. We analyzed published data and our own data to calculate rates of growth (g) and regression (d, decay) of tumors in patients with CRC correlating these results with the detection of circulating MT-KRAS DNA. Additionally we estimated mathematically the caloric burden of such tumors using data on mitotic and apoptotic indices. We conclude outgrowth of cells harboring intrinsic or acquired MT-KRAS cannot explain resistance to anti-EGFR (epidermal growth factor receptor) antibodies. Rates of tumor growth with panitumumab are unaffected by presence/absence of MT-KRAS. While MT-KRAS cells may be resistant to anti-EGFR antibodies, WT-KRAS cells also rapidly bypass this blockade suggesting inherent resistance mechanisms are responsible and a neutral evolution model is most appropriate. Using the above clinical data on tumor doubling times and mitotic and apoptotic indices we estimated the caloric intake required to support tumor growth and suggest it may explain in part cancer-associated cachexia.

Given that the insula plays a contributory role in the perception of chronic pain, we examined the resting-state functional connectivity between the insular cortex and other brain regions to investigate neural underpinnings of persisting perception of background pain in patients with complex regional pain syndrome (CRPS). A total of 25 patients with CRPS and 25 matched healthy controls underwent functional magnetic resonance imaging at rest. With the anterior and posterior insular cortices as seed regions, we compared the strength of the resting-state functional connectivity between the two groups. Functional connectivity between the anterior and posterior insular cortices and the postcentral and inferior frontal gyri, cingulate cortices was reduced in patients with CRPS compared with controls. Additionally, greater reductions in functional connectivity between the anterior insula and right postcentral gyrus were associated with more severe sensory pain in patients with CRPS (short-form McGill Pain Questionnaire sensory subscores, r = -.517, P = .023). The present results imply a possible role of the insula in aberrant processing of pain information in patients with CRPS. The findings suggest that a functional derangement of the connection between one of the somatosensory cortical functions of perception and one of the insular functions of awareness can play a significant role in the persistent experience of regional pain that is not confined to a specific nerve territory.

Background Serologic diagnosis is one of the most widely used diagnostic methods for Q fever, but the window period in antibody response of 2 to 3 weeks after symptom onset results in significant diagnostic delay. We investigated the diagnostic utility of Q fever PCR from formalin-fixed liver tissues in Q fever patients with acute hepatitis. Methods We reviewed the clinical and laboratory data in patients with Q fever hepatitis who underwent liver biopsy during a 17-year period, and whose biopsied tissues were available. We also selected patients who revealed granuloma in liver biopsy and with no Q fever diagnosis within the last 3 years as control. Acute Q fever hepatitis was diagnosed if two or more of the following clinical, serologic, or histopathologic criteria were met: (1) an infectious hepatitis-like clinical feature such as fever (≥ 38°C) with elevated hepatic transaminase levels; (2) exhibition of a phase II immunoglobulin G (IgG) antibodies titer by IFA of ≥ 1:128 in single determination, or a four-fold or greater rise between two separate samples obtained two or more weeks apart; (3) histologic finding of biopsy tissue showing characteristic fibrin ring granuloma. Results A total of 11 patients with acute Q fever hepatitis were selected and analyzed. Of the 11 patients, 3 (27%) had exposure to zoonotic risk factors and 7 (63%) met the serologic criteria. Granulomas with either circumferential or radiating fibrin deposition were observed in 10 cases on liver biopsy and in 1 case on bone marrow biopsy. 8 (73%) revealed positive Coxiella burnetii PCR from their formalin-fixed liver tissues. In contrast, none of 10 patients with alternative diagnosis who had hepatic granuloma revealed positive C. burnetii PCR from their formalin-fixed liver tissues. Conclusions Q fever PCR from formalin-fixed liver tissues appears to be a useful adjunct for diagnosing Q fever hepatitis.

Based on previous findings that ozone can induce an inflammatory response in the ocular surface of an animal model and in cultured human conjunctival epithelial cells, we investigated whether exposure to ozone exacerbates symptoms of allergic conjunctivitis. We evaluated the effects of exposure to ozone on conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, production of inflammatory cytokines in tears, and aqueous tear production in a mouse model of allergic conjunctivitis. To validate our in vivo results, we used interleukin (IL)-1α-pretreated conjunctival epithelial cells as an in vitro substitute for the mouse model. We evaluated whether exposure to ozone increased the inflammatory response and altered oxidative status and mitochondrial function in IL-1α-pretreated conjunctival epithelial cells. In the in vivo study, ozone induced increases in conjunctival chemosis, conjunctival injection, corneal and conjunctival fluorescein staining scores, and production of inflammatory cytokines, accompanied by a decrease in tear volume. In the in vitro study, exposure to ozone led to additional increases in IL-6 and tumor necrosis factor-α mRNA levels, which were already induced by treatment with IL-1α. Ozone did not induce any changes in cell viability. Pretreatment with IL-1α increased the expression of manganese superoxide dismutase, and exposure to ozone led to additional increments in the expression of this antioxidant enzyme. Ozone did not induce any changes in mitochondrial activity or expression of mitochondrial enzymes and proteins related to mitochondrial function, with the exception of phosphor-mammalian target of rapamycin. Treatment with butylated hydroxyanisole, a free radical scavenger, attenuated the ozone-induced increases in IL-6 expression in IL-1α-pretreated conjunctival epithelial cells. Therefore, we conclude that exposure to ozone exacerbates the detrimental effects on the integrity of the ocular surface caused by conjunctival allergic reactions, and further increases the inflammatory response in IL-1α-pretreated conjunctival epithelial cells.