Search

The woody Sonchus alliance, a spectacular example of adaptive radiation with six genera and approximately 31 species, is found exclusively on three Macaronesian Islands (Madeira, Canaries, and Cape Verdes) in the Atlantic Ocean. Four of the Sonchus taxa are restricted to Madeira, including shrubs and small trees at higher elevations (S. fruticosus and S. pinnatus), and caudex perennials in the lower coastal areas (S. ustulatus subsp. maderensis and S. ustulatus subsp. ustulatus). The Madeiran Sonchus stemmed from a single colonization event that originated from the Canaries < 3 million years ago. However, the plastome evolution and species relationships remains insufficiently explored. We therefore assembled and characterized the plastomes of four Sonchus taxa from Madeira and conducted a phylogenomic analysis. We found highly conserved plastome sequences among the taxa, further supporting a single and recent origin. We also found highly conserved plastomes among the cosmopolitan weedy Sonchus, Macaronesian Sonchus in the Atlantic, and Juan Fernández Islands Dendroseris in the Pacific. Furthermore, we identified four mutation hotspot regions (trnK-rps16, petN-psbM, ndhF-Ψycf1, and ycf1) and simple sequence repeat motifs. This study strongly supports the monophyly of Madeiran Sonchus. However, its relationship with the remaining woody Sonchus alliance from the Canary Islands requires further investigation.

Chloroplast genomes are valuable for inferring evolutionary relationships. We report the complete chloroplast genomes of 36 Corydalis spp. and one Fumaria species. We compared these genomes with 22 other taxa and investigated the genome structure, gene content, and evolutionary dynamics of the chloroplast genomes of 58 species, explored the structure, size, repeat sequences, and divergent hotspots of these genomes, conducted phylogenetic analysis, and identified nine types of chloroplast genome structures among Corydalis spp. The ndh gene family suffered inversion and rearrangement or was lost or pseudogenized throughout the chloroplast genomes of various Corydalis species. Analysis of five protein-coding genes revealed simple sequence repeats and repetitive sequences that can be potential molecular markers for species identification. Phylogenetic analysis revealed three subgenera in Corydalis. Subgenera Cremnocapnos and Sophorocapnos represented the Type 2 and 3 genome structures, respectively. Subgenus Corydalis included all types except type 3, suggesting that chloroplast genome structural diversity increased during its differentiation. Despite the explosive diversification of this subgenus, most endemic species collected from the Korean Peninsula shared only one type of genome structure, suggesting recent divergence. These findings will greatly improve our understanding of the chloroplast genome of Corydalis and may help develop effective molecular markers.

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.

Low-intensity transcranial focused ultrasound (tFUS) offers new functional neuromodulation opportunities, enabling stimulation of cortical as well as deep brain areas with high spatial resolution. Brain stimulation of awake sheep, in the absence of the confounding effects of anesthesia on brain function, provides translational insight into potential human applications with safety information supplemented by histological analyses. We examined the effects of tFUS pulsing parameters, particularly regarding pulse durations (PDs), on stimulating the cortical motor area (M1) and its thalamic projection in unanesthetized, awake sheep (n = 8). A wearable tFUS headgear, custom-made for individual sheep, enabled experiments to be conducted without using anesthesia. FUS stimuli, each 200 ms long, were delivered to the M1 and the thalamus using three different PDs (0.5, 1, and 2 ms) with the pulse repetition frequency (PRF) adjusted to maintain a 70% duty cycle at a derated in situ spatial-peak temporal-average intensity (Ispta) of 3.6 W/cm2. Efferent electromyography (EMG) responses to stimulation were quantified from both hind limbs. Group-averaged EMG responses from each of the hind limbs across the experimental conditions revealed selective responses from the hind limb contralateral to sonication. The use of 0.5 and 1 ms PDs generated higher EMG signal amplitudes compared to those obtained using a 2 ms PD. Faster efferent response was also observed from thalamic stimulation than that from stimulating the M1. Post-sonication behavioral observation and histological assessment performed 24 h and 1 month after sonication were not indicative of any abnormalities. The results suggest the presence of pulsing scheme-dependent effects of tFUS on brain stimulation and attest its safety in awake large animals.

ObjectivePulmonary 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.MethodsWe retrospectively reviewed the medical charts of patients with PAVMs between 2003 and 2021 at two tertiary referral hospitals and one secondary hospital.ResultsFifty-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).ConclusionOlder 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.

This study aimed to know how the general population recognizes live kidney donation in Korea. Participants were randomly selected from the general population after proportional allocation by region, sex, and age. Selected participants received a questionnaire that included demographic information, socioeconomic and marital statuses, prior recognition of live donor kidney transplantation, expected changes after donation, and the need for support after donor nephrectomy. Among the 1,000 participants from the web-based survey, 83.8% answered they fully understood living donor kidney transplantation, 81.1% knew about them, and 51.1% were willing to donate. Various complications after nephrectomy and deterioration in health after donation were the most significant reasons for those reluctant to donate. Most agreed that the government should provide social and economic support to living kidney donors, especially after exposure to the description of donor nephrectomy. Financial support, including surgery and regular medical check-up costs, was the most preferred government support. The Korean general population seemed aware of the value and safety of kidney donation, although only half of them were willing to donate due to concerns about possible complications. Most participants agreed on social and economic support for living kidney donors, especially surgery-related costs.

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.

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.

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.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.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.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.

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.

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.

Angiogenic peptides have therapeutic potential for the treatment of chronic ischemic diseases. Periostin, an extracellular matrix protein expressed in injured tissues, promotes angiogenesis and tissue repair. We previously reported that in vivo administration of both recombinant full-length protein and the first FAS I domain of periostin alleviated peripheral artery occlusive disease by stimulating the migration of humane endothelial colony forming cells (ECFCs) and subsequent angiogenesis. In the present study, we ascertained the peptide sequence responsible for the periostin-induced angiogenesis. By serial deletion mapping of the first FAS I domain, we identified a peptide sequence (amino acids 142-151) of periostin for stimulation of chemotactic migration, adhesion, proliferation and endothelial tube formation of human ECFCs in vitro. Chemotactic migration of ECFCs induced by the periostin peptide was blocked by pre-incubation with an anti-β5 integrin neutralizing antibody. Treatment of ECFCs with the periostin peptide led to phosphorylation of both AKT and ERK, and pretreatment of ECFCs with the MEK-ERK pathway inhibitor U0126 or the PI3K-AKT pathway inhibitors, LY294002 or Wortmannin, blocked the periostin peptide-stimulated migration of ECFCs. These results suggest that the synthetic periostin peptide can be applied for stimulating angiogenic and therapeutic potentials of ECFCs.

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.

We describe a wearable sensor developed for cardiac rehabilitation (CR) exercise. To effectively guide CR exercise, the dedicated CR wearable sensor (DCRW) automatically recommends the exercise intensity to the patient by comparing heart rate (HR) measured in real time with a predefined target heart rate zone (THZ) during exercise. The CR exercise includes three periods: pre-exercise, exercise with intensity guidance, and post-exercise. In the pre-exercise period, information such as THZ, exercise type, exercise stage order, and duration of each stage are set up through a smartphone application we developed for iPhones and Android devices. The set-up information is transmitted to the DCRW via Bluetooth communication. In the period of exercise with intensity guidance, the DCRW continuously estimates HR using a reflected pulse signal in the wrist. To achieve accurate HR measurements, we used multichannel photo sensors and increased the chances of acquiring a clean signal. Subsequently, we used singular value decomposition (SVD) for de-noising. For the median and variance of RMSEs in the measured HRs, our proposed method with DCRW provided lower values than those from a single channel-based method and template-based multiple-channel method for the entire exercise stage. In the post-exercise period, the DCRW transmits all the measured HR data to the smartphone application via Bluetooth communication, and the patient can monitor his/her own exercise history.

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.

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.

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.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.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.Q fever PCR from formalin-fixed liver tissues appears to be a useful adjunct for diagnosing Q fever hepatitis.

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.

Increased expression of adenylyl cyclase type 6 (AC6) has beneficial effects on the heart through cyclic adenosine monophosphate (cAMP)-dependent and cAMP-independent pathways. We previously generated a catalytically inactive mutant of AC6 (AC6mut) that has an attenuated response to β-adrenergic receptor stimulation, and, consequently, exhibits reduced myocardial cAMP generation. In the current study we test the hypothesis that cardiac-directed expression of AC6mut would protect the heart from sustained β-adrenergic receptor stimulation, a condition frequently encountered in patients with heart failure.AC6mut mice and transgene negative siblings received osmotic mini-pumps to provide continuous isoproterenol infusion for seven days. Isoproterenol infusion caused deleterious effects that were attenuated by cardiac-directed AC6mut expression. Both groups showed reduced left ventricular (LV) ejection fraction, but the reduction was less in AC6mut mice (p = 0.047). In addition, AC6mut mice showed superior left ventricular function, manifested by higher values for LV peak +dP/dt (p = 0.03), LV peak -dP/dt (p = 0.008), end-systolic pressure-volume relationship (p = 0.003) and cardiac output (p

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.

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

MicroRNAs (miRNAs) in blood plasma are stable under high levels of ribonuclease activity and could function in tissue-to-tissue communication, suggesting that they may have distinctive structural characteristics compared with non-circulating miRNAs. In this study, the expression of miRNAs in horse plasma and their characteristic nucleotide composition were examined and compared with non-plasma miRNAs. Highly expressed plasma miRNA species were not part of the abundant group of miRNAs in non-plasma tissues, except for the eca-let-7 family. eca-miR-486-5p, -92a, and -21 were among the most abundant plasma miRNAs, and their human orthologs also belong to the most abundant group of miRNAs in human plasma. Uracil and guanine were the most common nucleotides of both plasma and non-plasma miRNAs. Cytosine was the least common in plasma and non-plasma miRNAs, although levels were higher in plasma miRNAs. Plasma miRNAs also showed higher expression levels of miRNAs containing adenine and cytosine repeats, compared with non-plasma miRNAs. These observations indicate that miRNAs in the plasma have a unique nucleotide composition.

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.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.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

To investigate the association between blood 25-hydroxyvitamin D levels and pterygium.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.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).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.

Rodent-borne disease surveillance was conducted at Nightmare Range (NM-R), near the demilitarized zone in northeast Gyeonggi Province, Republic of Korea, to identify hemorrhagic fever with renal syndrome (HFRS) risks for a mountainous high-elevation (500 m) military training site. Monthly surveys were conducted from January 2008-December 2009. A total of 1,720 small mammals were captured belonging to the Orders Rodentia [Families, Sciuridae (1 species) and Muridae (7 species)] and Soricomorpha [Family, Soricidae (1species)]. Apodemus agrarius, the primary reservoir for Hantaan virus (HTNV), accounted for 89.9% (1,546) of all small mammals captured, followed by Myodes regulus (4.0%), Crocidura lasiura (3.9%), Micromys minutus (1.4%), Mus musculus (0.3%), Microtus fortis (0.2%), Apodemus peninsulae (0.2%), Tamias sibiricus (0.1%), and Rattus norvegicus (

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.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.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.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.

Endothelial progenitor cells (EPCs) can be isolated from human bone marrow or peripheral blood and reportedly contribute to neovascularization. Aptamers are 40-120-mer nucleotides that bind to a specific target molecule, as antibodies do. To utilize apatmers for isolation of EPCs, in the present study, we successfully generated aptamers that recognize human CD31, an endothelial cell marker. CD31 aptamers bound to human umbilical cord blood-derived EPCs and showed specific interaction with human CD31, but not with mouse CD31. However, CD31 aptamers showed non-specific interaction with CD31-negative 293FT cells and addition of polyanionic competitor dextran sulfate eliminated non-specific interaction without affecting cell viability. From the mixture of EPCs and 293FT cells, CD31 aptamers successfully isolated EPCs with 97.6% purity and 94.2% yield, comparable to those from antibody isolation. In addition, isolated EPCs were decoupled from CD31 aptamers with a brief treatment of high concentration dextran sulfate. EPCs isolated with CD31 aptamers and subsequently decoupled from CD31 aptamers were functional and enhanced the restoration of blood flow when transplanted into a murine hindlimb ischemia model. In this study, we demonstrated isolation of foreign material-free EPCs, which can be utilized as a universal protocol in preparation of cells for therapeutic transplantation.

Acute kidney injury (AKI) is a major risk factor in the development of chronic kidney disease (CKD). However, the mechanisms linking AKI to CKD remain unclear. We examined the alteration of macrophage phenotypes during an extended recovery period following ischemia/reperfusion injury (IRI) and determine their roles in the development of fibrosis.The left renal pedicle of mice was clamped for 40 min. To deplete monocyte/macrophage, liposome clodronate was injected or CD11b-DTR and CD11c-DTR transgenic mice were used.Throughout the phase of IRI recovery, M2-phenotype macrophages made up the predominant macrophage subset. On day 28, renal fibrosis was clearly shown with increased type IV collagen and TGF-β. The depletion of macrophages induced by the liposome clodronate injection improved renal fibrosis with a reduction of kidney IL-6, type IV collagen, and TGF-β levels. Additionally, the adoptive transfer of the M2c macrophages partially reversed the beneficial effect of macrophage depletion, whereas the adoptive transfer of the M1 macrophages did not. M2 macrophages isolated from the kidneys during the recovery phase expressed 2.5 fold higher levels of TGF-β than the M1 macrophages. The injection of the diphtheria toxin into CD11b or CD11c-DTR transgenic mice resulted in lesser depletion or no change in M2 macrophages and had little impact on renal fibrosis.Although M2 macrophages are known to be indispensible for short-term recovery, they are thought to be main culprit in the development of renal fibrosis following IRI.

In this study, we examined the effects of two phytoplankton species, Chlorella vulgaris and Stephanodiscus hantzschii, on growth of the zooplankton Daphnia magna. Our experimental approach utilized stable isotopes to determine the contribution of food algae to offspring characteristics and to the size of adult D. magna individuals. When equal amounts of food algae were provided (in terms of carbon content), the size of individuals, adult zooplankton, and their offspring increased significantly following the provision of S. hantzschii, but not after the provision of C. vulgaris or of a combination of the two species. Offspring size was unaffected when C. vulgaris or a mixture of the two algal species was delivered, whereas providing only S. hantzschii increased the production of larger-sized offspring. Stable isotope analysis revealed significant assimilation of diatom-derived materials that was important for the growth of D. magna populations. Our results confirm the applicability of stable isotope approaches for clarifying the contribution of different food algae and elucidate the importance of food quality for growth of D. magna individuals and populations. Furthermore, we expect that stable isotope analysis will help to further precisely examine the contribution of prey to predators or grazers in controlled experiments.

Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

To investigate the association between 25-hydroxyvitamin D and diabetic retinopathy (DR).A population-based cross-sectional study using a nation-wide, systemically stratified, multistage, clustered sampling method included a total of 18,363 subjects aged ≥ 40 years who participated in the Korean National Health and Nutrition Examination Survey during 2008-2012. All participants participated in standardized interviews, blood 25-hydroxyvitamin D level evaluations, and comprehensive ophthalmic examinations. Seven standard retinal fundus photographs were obtained from both eyes after pupil dilatation. DR was graded according to the modified Airlie House classification system.The blood 25-hydroxyvitamin D levels were 19.2 ng/mL in men and 17.9 ng/mL in women. After adjusting for potential confounders, including age, sex, diabetes duration, hemoglobin A1c levels, and hypertension, the odds ratios (OR) for any DR and proliferative DR among men decreased significantly in the highest blood 25-hydroxyvitamin D level quintile relative to the lowest quintile (OR, 0.37; 95% confidence interval [CI], 0.18-0.76; P for trend = 0.004 and OR, 0.15; 95% CI, 0.03-0.83; P for trend = 0.043).This study provides the first epidemiologic findings of the inverse relationships of blood 25-hydroxyvitamin D levels with any DR and proliferative DR only in men. Considering anti-angiogenic and anti-fibrotic action of vitamin D, further studies including longitudinal and interventional analysis are warranted.

With effective antiretroviral therapy (ART), cardiovascular diseases (CVD) are emerging as a major cause of morbidity and death in the aging HIV-infected population. To address whether HIV-Nef, a viral protein produced in infected cells even when virus production is halted by ART, can lead to endothelial activation and dysfunction, we tested Nef protein transfer to and activity in endothelial cells. We demonstrated that Nef is essential for major endothelial cell activating effects of HIV-infected Jurkat cells when in direct contact with the endothelium. In addition, we found that Nef protein in endothelial cells is sufficient to cause apoptosis, ROS generation and release of monocyte attractant protein-1 (MCP-1). The Nef protein-dependent endothelial activating effects can be best explained by our observation that Nef protein rapidly transfers from either HIV-infected or Nef-transfected Jurkat cells to endothelial cells between these two cell types. These results are of in vivo relevance as we demonstrated that Nef protein induces GFP transfer from T cells to endothelium in CD4.Nef.GFP transgenic mice and Nef is present in chimeric SIV-infected macaques. Analyzing the signal transduction effects of Nef in endothelial cells, we found that Nef-induced apoptosis is mediated through ROS-dependent mechanisms, while MCP-1 production is NF-kB dependent. Together, these data indicate that inhibition of Nef-associated pathways may be promising new therapeutic targets for reducing the risk for cardiovascular disease in the HIV-infected population.

The role of microRNAs (miRNAs) as a post-transcriptional gene regulator has been elucidated in a broad range of organisms including domestic animals. Characterization of miRNAs in normal tissues is an important step to investigate the functions of miRNAs in various physiological and pathological conditions. Using Illumina Next Generation Sequencing (NGS) technology, we identified a total of 292 known and 329 novel miRNAs in normal horse tissues including skeletal muscle, colon and liver. Distinct sets of miRNAs were differentially expressed in a tissue-specific manner. The miRNA genes were distributed across all the chromosomes except chromosomes 29 and 31 in the horse reference genome. In some chromosomes, multiple miRNAs were clustered and considered to be polycistronic transcript. A base composition analysis showed that equine miRNAs had a higher frequency of A+U than G+C. Furthermore, U tended to be more frequent at the 5' end of miRNA sequences. This is the first experimental study that identifies and characterizes the global miRNA expression profile in normal horse tissues. The present study enriches the horse miRNA database and provides useful information for further research dissecting biological functions of miRNAs in horse.

PURPOSE: To elucidate the prevalence of cataract, glaucoma, pterygia, and diabetic retinopathy among Korean postmenopausal women with or without estrogen replacement therapy (ERT). METHODS: A cross-sectional, nationally representative sample from the 4th Korea National Health and Nutrition Examination Survey (KNHANES IV) (2007-2009) was used. Participants were interviewed for the determination of socioeconomic and gynecologic factors. Each woman also underwent an ophthalmologic examination and provided a blood sample for risk factor assessment. RESULTS: Of 3968 postmenopausal women enrolled, 3390 had never received estrogen, and 578 were undergoing estrogen treatment. After adjusting for age, diabetes, hypertension, high cholesterol levels, and high low-density lipoprotein levels, the prevalence of anterior polar cataract, retinal nerve fiber layer (RNFL) defect, and flesh pterygium was higher in the non-ERT group (OR, 3.24; 95% CI, 1.12-9.35, OR 1.70; 95% CI, 1.04-2.78, OR 3.725; 95% CI, 1.21-11.45, respectively). Further, the prevalence of atrophic pterygium was lower in the non-ERT group compared to that in the ERT group (OR, 0.21, 95% CI, 0.07-0.63). CONCLUSIONS: These data suggest that ERT has a protective effect against the development of anterior polar cataract, flesh pterygium, and RNFL defect.

Lactobacillus plantarum DK119 (DK119) isolated from the fermented Korean cabbage food was used as a probiotic to determine its antiviral effects on influenza virus. DK119 intranasal or oral administration conferred 100% protection against subsequent lethal infection with influenza A viruses, prevented significant weight loss, and lowered lung viral loads in a mouse model. The antiviral protective efficacy was observed in a dose and route dependent manner of DK119 administration. Mice that were treated with DK119 showed high levels of cytokines IL-12 and IFN-γ in bronchoalveolar lavage fluids, and a low degree of inflammation upon infection with influenza virus. Depletion of alveolar macrophage cells in lungs and bronchoalveolar lavages completely abrogated the DK119-mediated protection. Modulating host innate immunity of dendritic and macrophage cells, and cytokine production pattern appeared to be possible mechanisms by which DK119 exhibited antiviral effects on influenza virus infection. These results indicate that DK119 can be developed as a beneficial antiviral probiotic microorganism.

PURPOSE: To examine the prevalence and risk factors of refractive errors in a representative Korean population aged 20 years old or older. METHODS: A total of 23,392 people aged 20+ years were selected for the Korean National Health and Nutrition Survey 2008-2011, using stratified, multistage, clustered sampling. Refractive error was measured by autorefraction without cycloplegia, and interviews were performed regarding associated risk factors including gender, age, height, education level, parent's education level, economic status, light exposure time, and current smoking history. RESULTS: Of 23,392 participants, refractive errors were examined in 22,562 persons, including 21,356 subjects with phakic eyes. The overall prevalences of myopia (< -0.5 D), high myopia (< -6.0 D), and hyperopia (> 0.5 D) were 48.1% (95% confidence interval [CI], 47.4-48.8), 4.0% (CI, 3.7-4.3), and 24.2% (CI, 23.6-24.8), respectively. The prevalence of myopia sharply decreased from 78.9% (CI, 77.4-80.4) in 20-29 year olds to 16.1% (CI, 14.9-17.3) in 60-69 year olds. In multivariable logistic regression analyses restricted to subjects aged 40+ years, myopia was associated with younger age (odds ratio [OR], 0.94; 95% Confidence Interval [CI], 0.93-0.94, p < 0.001), education level of university or higher (OR, 2.31; CI, 1.97-2.71, p < 0.001), and shorter sunlight exposure time (OR, 0.84; CI, 0.76-0.93, p = 0.002). CONCLUSIONS: This study provides the first representative population-based data on refractive error for Korean adults. The prevalence of myopia in Korean adults in 40+ years (34.7%) was comparable to that in other Asian countries. These results show that the younger generations in Korea are much more myopic than previous generations, and that important factors associated with this increase are increased education levels and reduced sunlight exposures.