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Abstract Aim This study was conducted to develop an electrocardiogram education program that incorporates an HTML webpage and blended learning methods to enhance electrocardiogram interpretation skills. Through continual and efficient education, the program aims to assist nurses in providing appropriate care and treatment to patients. Design Pre-post design study. Methods We developed an electrocardiogram interpretation HTML webpage based on an electrocardiogram interpretation algorithm and implemented an 18-week (2023.5.15 ~ 2023.9.22) electrocardiogram education program, which included daily 5-minute training sessions. Twenty-seven ward nurses were provided with the URL ( https://ecgweb.github.io/ECGwebEN ) to the electrocardiogram interpretation HTML webpage and shared one electrocardiogram case daily for self-interpretation. Electrocardiogram interpretation performance and confidence were evaluated through questionnaires at three phases: before the program, after 6 weeks of basic electrocardiogram and arrhythmia education, and after 12 weeks of application of the electrocardiogram interpretation HTML webpage and case-based lecture education. The statistical tests used were repeated-measures ANOVA or the Wilcoxon signed-rank test. Results The average score for electrocardiogram interpretation performance before the electrocardiogram education program was 11.89(SD = 3.50), after 6 weeks of basic electrocardiogram and arrhythmia education it was 14.15(SD = 3.68), and after 12 weeks of application of the electrocardiogram interpretation HTML webpage and case-based lecture education, it was 15.56(SD = 3.04). This shows that electrocardiogram interpretation performance significantly improved over time (p

Abstract Background Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive. Methods In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. Results We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy. Conclusions Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients.

Abstract Background The association between the adiponectin‐to‐leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. Methods In this prospective community‐based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of

Bacteriophages (phages) that infect bacterial pathogens are an alternative means of controlling bacterial diseases in humans, animals, and plants. However, the effects of targeted phage therapy on indigenous microbial communities are not fully understood. In this study, we hypothesized that phages infecting plant pathogenic bacteria play a role in modulating the microbial community in the plant rhizosphere. To explore this, we used the soil-borne plant bacterial pathogen Ralstonia pseudosolanacearum as the host bacterium and its phages as a model system in the tomato rhizosphere. The effect of phages on the microbiota was examined using a narrow host range phage RpY1 and a combination of two phages (RpY2 and RpT1, termed the phage combo) with a broad host range under the natural rhizosphere microbiota of tomato plants. Both RpY1 and the phage combo altered the tomato rhizosphere microbiota. The phage combo displayed phage effects mostly in the presence of R. pseudosolanacearum. However, RpY1 affected the rhizosphere microbiota even in the absence of the host bacterium. The effect of phage RpY1 on the microbiota was further investigated in the tomato rhizosphere using a synthetic community (SynCom) mimicking the natural tomato rhizosphere microbiota. Phage RpY1 affected the microbial community structure of the SynCom in the tomato rhizosphere in the absence of the host bacterium. Analyses of the natural microbiota and SynCom in the tomato rhizosphere indicated an indirect effect of phage RpY1 on the microbiota. This study suggests that phage application modulates the indigenous microbiota through unknown interactions with nonhost bacterial members in the plant rhizosphere. [Graphic: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Psoriasis is an inflammatory skin disease characterized by the hyperproliferative epidermal keratinocytes and significant immune cells infiltration, leading to cytokines production such as IL-1β, TNF-α, IL-23, and IL-17. Recent study highlights the critical role of IL-1β in the induction and activation of pathogenic Th17 and IL-17-producing γδ T cells, contributing to psoriasis. However, the mechanism underlying IL-1β dysregulation in psoriasis pathogenesis is unclear. Autophagy regulates IL-1β production and has a pleiotropic effect on inflammatory disorders. Previous studies showed controversial role of autophagy in psoriasis pathogenesis, either pro-inflammatory in autophagy-deficient keratinocyte or anti-inflammatory in pharmacologically autophagy-promoting macrophages. Thus, the direct role of autophagy and its therapeutic potential in psoriasis remains unclear. Methods We used myeloid cell-specific autophagy-related gene 7 (Atg7)-deficient mice and determined the effect of autophagy deficiency in myeloid cells on neutrophilia and disease pathogenesis in an imiquimod-induced psoriasis mouse model. We then assessed the pathogenic mechanism focusing on immune cells producing IL-1β and IL-17 along with gene expression profiles associated with psoriasis in mouse model and public database on patients. Moreover, therapeutic potential of IL-1β blocking in such context was assessed. Results We found that autophagy deficiency in myeloid cells exacerbated neutrophilic inflammation and disease pathogenesis in mice with psoriasis. This autophagy-dependent effect was associated with a significant increase in IL-1β production from myeloid cells, particularly macrophages, Cxcl2 expression, and IL-17 A producing T cells including γδ T cells. Supporting this, treatment with systemic IL-1 receptor blocking antibody or topical saccharin, a disaccharide suppressing pro-IL-1β expression, led to the alleviation of neutrophilia and psoriatic skin inflammation linked to autophagy deficiency. The pathophysiological relevance of this finding was supported by dysregulation of autophagy-related genes and their correlation with Th17 cytokines in psoriatic skin lesion from patients with psoriasis. Conclusions Our results suggest that autophagy dysfunction in myeloid cells, especially macrophages, along with IL-1β dysregulation has a causal role in neutrophilic inflammation and psoriasis pathogenesis.

The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP

Abstract The inner ear is the hub where hair cells (HCs) transduce sound, gravity, and head acceleration stimuli to the brain. Hearing and balance rely on mechanosensation, the fastest sensory signals transmitted to the brain. The mechanoelectrical transducer (MET) channel is the entryway for the sound-balance-brain interface, but the channel-complex composition is not entirely known. Here, we report that the mouse utilizes Piezo1 (Pz1) and Piezo2 (Pz2) isoforms as MET-complex components. The Pz channels, expressed in HC stereocilia, and cell lines are co-localized and co-assembled with MET complex partners. Mice expressing non-functional Pz1 and Pz2 at the ROSA26 locus have impaired auditory and vestibular traits that can only be explained if the Pzs are integral to the MET complex. We suggest that Pz subunits constitute part of the MET complex and that interactions with other MET complex components yield functional MET units to generate HC MET currents.

Introduction: High sodium intake is associated with increased proteinuria. Herein, we investigated whether proteinuria could modify the association between urinary sodium excretion and adverse kidney outcomes in patients with chronic kidney disease (CKD). Methods: In this prospective observational cohort study, we included 967 participants with CKD stages G1 to G5 between 2011 and 2016, who measured 24-hour urinary sodium and protein excretion at baseline. The main predictors were urinary sodium and protein excretion levels. The primary outcome was CKD progression, which was defined as a ≥50% decline in the estimated glomerular filtration rate (eGFR) or the onset of kidney replacement therapy. Results: During a median follow-up period of 4.1 years, the primary outcome events occurred in 287 participants (29.7%). There was a significant interaction between proteinuria and sodium excretion for the primary outcome (P = 0.006). In patients with proteinuria of

Head and neck squamous cell carcinomas (HNSCCs) undergo a stepwise progression from normal tissues. In order to better understand the molecular mechanisms behind such progression, here the authors profile HNSCC tumors at different stages using single-cell RNA-seq, and observe the role of interactions with the tumor microenvironment.

Abstract Iron plays an important role in hemodynamics and the immunity, independent of anemia. Since dynamic changes occur in iron storage after kidney transplantation (KT), we investigated the association between iron status and kidney outcomes in KT patients. We analyzed data from the KoreaN cohort study for Outcome in patients With KT (KNOW-KT). The iron status was classified into three groups based on ferritin or transferrin saturation (TSAT) levels one year after KT, with reference ranges of 20‒35% and 100‒300 ng/mL for TSAT and ferritin, respectively. The primary outcome was the composite outcome, which consisted of death, graft failure, and an estimated glomerular filtration rate decline ≥ 50%. In total, 895 patients were included in the final analysis. During a median follow-up of 5.8 years, the primary outcome occurred in 94 patients (19.8/1000 person-years). TSAT levels decreased one year after KT and thereafter gradually increased, whereas ferritin levels were maintained at decreased levels. The adjusted hazard ratios (95% confidence intervals) for the composite outcome were 1.67 (1.00–2.77) and 1.20 (0.60–2.40) in the TSAT > 35% and ferritin > 300 ng/mL groups, respectively. High iron status with high TSAT levels increases the risk of graft failure or kidney functional deterioration after KT.

Abstract The aggressive proliferation of tumor cells often requires increased glucose uptake and excessive anaerobic glycolysis, leading to the massive production and secretion of lactate to form a unique tumor microenvironment (TME). Therefore, regulating appropriate lactate levels in the TME would be a promising approach to control tumor cell proliferation and immune suppression. To effectively consume lactate in the TME, lactate oxidase (LOX) and catalase (CAT) were displayed onto Aquifex aeolicus lumazine synthase protein nanoparticles (AaLS) to form either AaLS/LOX or AaLS/LOX/CAT. These complexes successfully consumed lactate produced by CT26 murine colon carcinoma cells under both normoxic and hypoxic conditions. Specifically, AaLS/LOX generated a large amount of H2O2 with complete lactate consumption to induce drastic necrotic cell death regardless of culture condition. However, AaLS/LOX/CAT generated residual H2O2, leading to necrotic cell death only under hypoxic condition similar to the TME. While the local administration of AaLS/LOX to the tumor site resulted in mice death, that of AaLS/LOX/CAT significantly suppressed tumor growth without any severe side effects. AaLS/LOX/CAT effectively consumed lactate to produce adequate amounts of H2O2 which sufficiently suppress tumor growth and adequately modulate the TME, transforming environments that are favorable to tumor suppressive neutrophils but adverse to tumor-supportive tumor-associated macrophages. Collectively, these findings showed that the modular functionalization of protein nanoparticles with multiple metabolic enzymes may offer the opportunity to develop new enzyme complex-based therapeutic tools that can modulate the TME by controlling cancer metabolism. Graphical Abstract

Background Globally, since 1 January 2020 and as of 24 January 2023, there have been over 664 million cases of COVID-19 and over 6.7 million deaths reported to WHO. WHO developed an evidence-based alert system, assessing public health risk on a weekly basis in 237 countries, territories and areas from May 2021 to June 2022. This aimed to facilitate the early identification of situations where healthcare capacity may become overstretched.Methods The process involved a three-stage mixed methods approach. In the first stage, future deaths were predicted from the time series of reported cases and deaths to produce an initial alert level. In the second stage, this alert level was adjusted by incorporating a range of contextual indicators and accounting for the quality of information available using a Bayes classifier. In the third stage, countries with an alert level of ‘High’ or above were added to an operational watchlist and assistance was deployed as needed.Results Since June 2021, the system has supported the release of more than US$27 million from WHO emergency funding, over 450 000 rapid antigen diagnostic testing kits and over 6000 oxygen concentrators. Retrospective evaluation indicated that the first two stages were needed to maximise sensitivity, where 44% (IQR 29%–67%) of weekly watchlist alerts would not have been identified using only reported cases and deaths. The alerts were timely and valid in most cases; however, this could only be assessed on a non-representative sample of countries with hospitalisation data available.Conclusions The system provided a standardised approach to monitor the pandemic at the country level by incorporating all available data on epidemiological analytics and contextual assessments. While this system was developed for COVID-19, a similar system could be used for future outbreaks and emergencies, with necessary adjustments to parameters and indicators.

Abstract Background Immunotherapies have been gaining attention for the prevention of cancer recurrence and metastasis. Cancer immunotherapy can induce memory cells to target cancer-specific antigens and, thus, selectively kill cancer cells. However, there are difficulties in inducing cancer antigen–specific immunity due to limited knowledge regarding cancer antigens. In this study, we synthesized a dual-functional hydrogel to induce antigen generation and immune activation. Results To elicit a cancer self-antigen–specific immune response, we synthesized an alginate-collagen–based injectable hydrogel, called thermally responsive hydrogel (pTRG), which was incorporated with indocyanine green and the immune stimulator polyinosinic:polycytidylic acid (poly I:C). pTRG was evaluated for its anticancer and anti-metastatic effects against CT-26 carcinoma and 4T1 breast tumor in mice by combining photothermal therapy (PTT) and immunotherapy. Near-infrared (NIR) irradiation promoted temperature elevation in pTRG, consequently exerting a therapeutic effect on mouse tumors. Lung metastasis was prevented in cured CT-26 tumor-injected mice following pTRG treatment via cancer antigen–specific T cell immunity. Moreover, pTRG successfully eliminated the original tumor in 4T1 tumor-bearing mice via PTT and protected them from lung metastasis. To further evaluate the carrier function of TRGs, different types of immunotherapeutic molecules were incorporated into TRGs, which led to the effective elimination of the first CT-26 tumor and the prevention of lung metastasis. Conclusions Our data demonstrate that TRG is a efficient material not only for treating primary tumors but also for preventing metastasis and recurrence.

The demand for face masks is increasing exponentially due to the coronavirus pandemic and the particulate matter (PM) in the atmosphere. As a result, an enormous number of disposable mask filters have been produced and discarded, contributing to plastic waste. Underprivileged people who cannot afford to purchase commercial face masks have started making fabric masks with waste clothing; however, this material does not effectively filter viruses or PM. Therefore, in this study, a chitosan coating was applied to clothing fabrics to increase their effectiveness as face masks. The improvement in the PM removal efficiency owing to the chitosan polymer was observed for stocking, innerwear, and bamboo materials, but not for cotton. Furthermore, chitosan prepared in the form of a nanowhisker (CsW) achieved a PM 2.5 removal efficiency of 96% in a five-layer cotton fabric. In addition, a commercial biodegradable poly(lactic acid) filter was coated with CsW, which increased the PM 2.5 removal efficiency from 67% to 83%. Additionally, microbial growth was significantly suppressed in the chitosan-coated fabrics, and the degree to which it was suppressed depended on the coating concentration. The study will aid in the utilization of face mask filters that are more sustainable, efficient, and widely accessible.

Background Long-term outcomes of live kidney donors remain controversial, although this information is crucial for selecting potential donors. Thus, this study compared the long-term risk of all-cause mortality between live kidney donors and healthy control. Methods We performed a retrospective cohort study including donors from seven tertiary hospitals in South Korea. Persons who underwent voluntary health screening were included as controls. We created a matched control group considering age, sex, era, body mass index, baseline hypertension, diabetes, estimated glomerular filtration rate, and dipstick albuminuria. The study outcome was progression to end-stage kidney disease (ESKD), and all-cause mortality as identified in the linked claims database. Results We screened 1,878 kidney donors and 78,115 health screening examinees from 2003 to 2016. After matching, 1,701 persons remained in each group. The median age of the matched study subjects was 44 years, and 46.6% were male. Among the study subjects, 2.7% and 16.6% had underlying diabetes and hypertension, respectively. There were no ESKD events in the matched donor and control groups. There were 24 (1.4%) and 12 mortality cases (0.7%) in the matched donor and control groups, respectively. In the age-sex adjusted model, the risk for all-cause mortality was significantly higher in the donor group than in the control group. However, the significance was not retained after socioeconomic status was included as a covariate (adjusted hazard ratio, 1.82; 95% confidence interval, 0.87–3.80). Conclusion All-cause mortality was similar in live kidney donors and matched non-donor healthy controls with similar health status and socioeconomic status in the Korean population.

Abstract Among plastic items, single‐use straws are particularly detrimental to marine ecosystems because such straws, including those made of poly(lactic acid) (PLA), are sharp and extremely slowly degradable in the ocean. While paper straws are promising alternatives, they exhibit hydration‐induced swelling even when coated with a non‐degradable plastic coating and promote effervescence (fizzing) in soft drinks owing to their surface heterogeneities. In this study, upgraded paper straw is coated with poly(butylene succinate) cellulose nanocrystal (PBS/CNC) composites. CNC increases adhesion to paper owing to their similar chemical structures, optimizes crystalline PBS spherulites through effective nucleation, and reinforces the matrix through its anisotropic and rigid features. The straws are not only anti‐fizzing when used with soft drinks owing to their homogeneous and seamless surface coatings, but also highly water‐resistant and tough owing to their watertight surfaces. All degradable components effectively decompose under aerobic composting and in the marine environment. This technology contributes to United Nations Sustainable Development Goal 14 (Life Below Water).

Background Considering the growing prevalence of Western lifestyles and related chronic diseases occurring in South Korea, this study aimed to explore the progression of metabolic risk factors in living kidney donors. Methods This study enrolled living kidney donors from seven hospitals from 1982 to 2016. The controls were individuals that voluntarily received health check-ups from 1995 to 2016 that were matched with donors according to age, sex, diabetes status, baseline estimated glomerular filtration rate, and date of the medical record. Data on hyperuricemia, hypertension, hypercholesterolemia, and overweight/obesity were collected to determine metabolic risks. Logistic regressions with interaction terms between the medical record date and donor status were used to compare the trends in metabolic risks over time in the two groups. Results A total of 2,018 living kidney donors and matched non-donors were included. The median age was 44.0 years and 54.0% were women. The living kidney donors showed a lower absolute prevalence for all metabolic risk factors, except for those that were overweight/obese, than the non-donors. The proportion of subjects that were overweight/obese was consistently higher over time in the donor group. The changes over time in the prevalence of each metabolic risk were not significantly different between groups, except for a lower prevalence of metabolic risk factors ≥ 3 in donors. Conclusion Over time, metabolic risks in living kidney donors are generally the same as in non-donors, except for a lower prevalence of metabolic risk factors ≥3 in donors.

DksA with (p)ppGpp regulates a wide range of gene transcriptions during the stringent response. The aim of this study was to identify a DksA ortholog in Acinetobacter baumannii and clarify the roles of DksA in bacterial physiology and virulence. The ∆dksA mutant and its complemented strains were constructed using A. baumannii ATCC 17978. The AlS_0248 in A. baumannii ATCC 17978 was identified to dksA using sequence homology, protein structure prediction, and gene expression patterns under different culture conditions. The ∆dksA mutant strain showed a filamentous morphology compared with the wild-type (WT) strain. Bacterial growth was decreased in the ∆dksA mutant strain under static conditions. Surface motility was decreased in the ∆dksA mutant strain compared with the WT strain. In contrast, biofilm formation was increased and biofilm-associated genes, such as bfmR/S and csuC/D/E, were upregulated in the ∆dksA mutant strain. The ∆dksA mutant strain produced less autoinducers than the WT strain. The expression of abaI and abaR was significantly decreased in the ∆dksA mutant strain. Furthermore, the ∆dksA mutant strain showed less bacterial burden and milder histopathological changes in the lungs of mice than the WT strain. Mice survival was also significantly different between the ∆dksA mutant and WT strains. Conclusively, DksA is directly or indirectly involved in regulating a wide range of genes associated with bacterial physiology and virulence, which contributes to the pathogenesis of A. baumannii. Thus, DksA is a potential anti-virulence target for A. baumannii infection.

Background: Ginsenosides have beneficial effects on several airway inflammatory disorders primarily through glucocorticosteroid-like anti-inflammatory activity. Among inflammatory cells, eosinophils play a major pathogenic role in conferring a risk of severe refractory diseases including chronic rhinosinusitis (CRS). However, the role of ginsenosides in reducing eosinophilic inflammation and CRS pathogenesis is unexplored. Methods: We investigated the therapeutic efficacy and underlying mechanism of ginsenoside F1 (G-F1) in comparison with those of dexamethasone, a representative glucocorticosteroid, in a murine model of CRS. The effects of G-F1 or dexamethasone on sinonasal abnormalities and infiltration of eosinophils and mast cells were evaluated by histological analyses. The changes in inflammatory cytokine levels in sinonasal tissues, macrophages, and NK cells were assessed by qPCR, ELISA, and immunohistochemistry. Results: We found that G-F1 significantly attenuated eosinophilic inflammation, mast cell infiltration, epithelial hyperplasia, and mucosal thickening in the sinonasal mucosa of CRS mice. Moreover, G-F1 reduced the expression of IL-4 and IL-13, as well as hematopoietic prostaglandin D synthase required for prostaglandin D2 production. This therapeutic efficacy was associated with increased NK cell function, without suppression of macrophage inflammatory responses. In comparison, dexamethasone potently suppressed macrophage activation. NK cell depletion nullified the therapeutic effects of G-F1, but not dexamethasone, in CRS mice, supporting a causal link between G-F1 and NK cell activity. Conclusion: Our results suggest that potentiating NK cell activity, for example with G-F1, is a promising strategy for resolving eosinophilic inflammation in CRS.

Exosome-based drug delivery is emerging as a promising field with the potential to revolutionize therapeutic interventions. Exosomes, which are small extracellular vesicles released by various cell types, have attracted significant attention due to their unique properties and natural ability to transport bioactive molecules. These nano-sized vesicles, ranging in size from 30 to 150 nm, can effectively transport a variety of cargoes, including proteins, nucleic acids, and lipids. Compared to traditional drug delivery systems, exosomes exhibit unique biocompatibility, low immunogenicity, and reduced toxicity. In addition, exosomes can be designed and tailored to improve targeting efficiency, cargo loading capacity, and stability, paving the way for personalized medicine and precision therapy. However, despite the promising potential of exosome-based drug delivery, its clinical application remains challenging due to limitations in exosome isolation and purification, low loading efficiency of therapeutic cargoes, insufficient targeted delivery, and rapid elimination in circulation. This comprehensive review focuses on the transition of exosome-based drug delivery from the bench to clinic, highlighting key aspects, such as exosome structure and biogenesis, cargo loading methods, surface engineering techniques, and clinical applications. It also discusses challenges and prospects in this emerging field.

Abstract Background Zinc uptake-regulator (Zur)-regulated lipoprotein A (ZrlA) plays a role in bacterial fitness and overcoming antimicrobial exposure in Acinetobacter baumannii. This study further characterized the zrlA gene and its encoded protein and investigated the roles of the zrlA gene in bacterial morphology, antimicrobial susceptibility, and production of outer membrane vesicles (OMVs) in A. baumannii ATCC 17978. Results In silico and polymerase chain reaction analyses showed that the zrlA gene was conserved among A. baumannii strains with 97–100% sequence homology. Recombinant ZrlA protein exhibited a specific enzymatic activity of D-alanine-D-alanine carboxypeptidase. Wild-type A. baumannii exhibited more morphological heterogeneity than a ΔzrlA mutant strain during stationary phase. The ΔzrlA mutant strain was more susceptible to gentamicin than the wild-type strain. Sizes and protein profiles of OMVs were similar between the wild-type and ΔzrlA mutant strains, but the ΔzrlA mutant strain produced 9.7 times more OMV particles than the wild-type strain. OMVs from the ΔzrlA mutant were more cytotoxic in cultured epithelial cells than OMVs from the wild-type strain. Conclusions The present study demonstrated that A. baumannii ZrlA contributes to bacterial morphogenesis and antimicrobial resistance, but its deletion increases OMV production and OMV-mediated host cell cytotoxicity.

In 2019, symptoms of Botrytis mold on the peony (Paeonia lactiflora Pall.) 'Sarah Bernhardt' were observed during a survey of the commercial greenhouses of Gangjin County, South Korea. The initial symptoms, small brown spots, were observed mainly at the leaf margins. The lesions extended to the interior of leaves forming irregular spots in which abundant conidia developed. Fungal colonies were obtained from surface-sterilized tissue excised from growing edges of the lesions that were transferred to potato dextrose agar. Melanized irregular sclerotia were formed in these colonies after 40 days at 8°C. Molecular phylogeny based on sequences of genes for glyceraldehyde-3-phosphate dehydrogenase, heat-shock protein 60, and RNA polymerase subunit II were highest for the PBC-2 isolate to the type strains of Botrytis cinerea, rather than other Botrytis species associated with peony diseases. Following Koch's postulates, healthy Sarah Bernhardt plants were inoculated with a foliar application of conidial suspensions of the isolate PBC-2. Following incubation under humidity with a 12 hr photoperiod for 7 days, symptoms developed on the leaf margins that were identical to those observed in the greenhouses. This study is the first report of Botrytis blight caused by B. cinerea on peonies grown in commercial greenhouses in South Korea.

Purpose This is the first study to examine whether age impacts the response of single muscle fibers to high/low frequency and high/low volume electrical pulse stimulation. We performed in vitro experiments to evaluate the effect of low-frequency high-volume electrical pulse stimulation (EPS) on mechanistic target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK) signaling pathway, and satellite cell activation in singles fibers of young and aged muscles. Methods Isolated single fibers from gastocnemius in 12-wk (n=21) and 72-wk (n=21) old male C57BL/6 mice were divided into four groups: 1) control (Con) received no EPS, 2) low-frequency low-volume EPS (LL), 3) low-frequency high-volume EPS (LH), and 4) high-frequency low-volume EPS (HL) were made to contract using independent EPS protocols. Satellite cell activation and anabolic pathway (mTOR and MAPK signaling) were measured before and after EPS. Results The number of quiescent (Pax7+/Ki67-) and active (Pax7+/Ki67+) satellite cells, myonuclear content and the phosphorylation of 4E-BP1 and ERK were higher in young when compared with old. However, regardless of age, LH and HL EPS significantly increased the number of activate satellite cells (142%, both) and phosphorylation of mTOR (129% and 133%, respectively), p70S6K (133% and 136%, respectively) and 4E-BP1 (140% and 129%, respectively) compared with Con. The protein expression of ERK phosphorylation only increased by LH EPS in both the young and old groups (123% and 125%, respectively). Conclusion Low-frequency high-volume EPS stimulated satellite cell activation and the mTOR signaling pathway in older similar to young muscle.

Mechanosensation – by which mechanical stimuli are converted into a neuronal signal – is the basis for the sensory systems of hearing, balance, and touch. Mechanosensation is unmatched in speed and its diverse range of sensitivities, reaching its highest temporal limits with the sense of hearing; however, hair cells (HCs) and the auditory nerve (AN) serve as obligatory bottlenecks for sounds to engage the brain. Like other sensory neurons, auditory neurons use the canonical pathway for neurotransmission and millisecond-duration action potentials (APs). How the auditory system utilizes the relatively slow transmission mechanisms to achieve ultrafast speed, and high audio-frequency hearing remains an enigma. Here, we address this paradox and report that the mouse, and chinchilla, AN are mechanically sensitive, and minute mechanical displacement profoundly affects its response properties. Sound-mimicking sinusoidal mechanical and electrical current stimuli affect phase-locked responses. In a phase-dependent manner, the two stimuli can also evoke suppressive responses. We propose that mechanical sensitivity interacts with synaptic responses to shape responses in the AN, including frequency tuning and temporal phase locking. Combining neurotransmission and mechanical sensation to control spike patterns gives the mammalian AN a secondary receptor role, an emerging theme in primary neuronal functions.

The prognosis of patients who are comatose after resuscitation remains uncertain. The accurate prediction of neurological outcome is important for management decisions and counseling. A neurological examination is an important factor for prognostication, but widely used sedatives alter the neurological examination and delay the response recovery. Additional studies including electroencephalography, somatosensory-evoked potentials, brain imaging, and blood biomarkers are useful for evaluating the extent of brain injury. This review aimed to assess the usefulness of and provide practical prognostic strategy for pediatric postresuscitation patients. The principles of prognostication are that the assessment should be delayed until at least 72 hours after cardiac arrest and the assessment should be multimodal. Furthermore, multiple factors including unmeasured confounders in individual patients should be considered when applying the prognostication strategy.

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.

Sialyltransferase, an enzyme responsible for attaching sialic acid to the cell surface, is reported to play a key role in cancer, making sialyltransferase a potential therapeutic target in drug development. Several methods have been developed to quantify sialic acids in biological samples however limitations exists and quantification in complex cell matrices lack investigation. Hence, this paper outlines a simple method to detect and quantify sialic acids in cancer cells for evaluating sialyltransferase activity of potential therapeutic compounds. An efficient method was developed using a reverse-phase ion-pairing HPLC-UV using triisopropanolamine as the ion-pairing agent with a C18 column. Neu5Ac was successfully eluted with the retention time 6.344 min with a flow rate of 0.4 mL/min. The proposed method was validated appropriately according to the AOAC guidelines (2013). This work demonstrates that the proposed method is not only relatively simple but also cost and time effective compared to pre-existing methods to successfully determine both free and protein-bound Neu5Ac in a complex cancer cell matrix. Furthermore, by applying the proposed method, a statistically significant decrease was observed for both HeLa and HuCCT1 cell lines with the application of deoxycholic acid-a known sialyltransferase inhibitor. Hence, the proposed method seems promisingly applicable to evaluate the effectiveness of potential sialyltransferase inhibitors.

Background : Numerous researchers have worked to develop treatments for obesity; however, the prevalence of obesity continues to increase in many countries. Moreover, the effects of physical activity and exercise on obesity remain unclear. Therefore, it is necessary to perform a systematic review and meta-analysis to assess the relationship between exercise and obesity using mediator variables such as the mode of exercise. Methods : Our review focuses on research tracking the effects of exercise on obesity conducted from 2007 to 2016 and available in any of three databases: Embase, PubMed, and EBSCO Academic Search Premier. The keywords used in the search were exercise and obesity and exercise and obese. Results : The average size of the effects that exercise interventions have on body mass index (standardized mean difference [SMD], 0.533), waist circumference (SMD, 0.666), total cholesterol (SMD, 0.721), and triglyceride (TG; SMD, 0.603) were medium or larger. Exercise had greater effects on the outward appearance of obesity (body mass index, waist circumference) than on its practical factors (weight, % body fat). The effect of exercise on TG (SMD, 0.603) was larger than that on low-density lipoprotein (SMD, 0.406) and high-density lipoprotein (SMD, –0.222). Exercise duration (weeks of exercise) and intensity correlate better than exercise time (minutes per week) with a large and consistent improvement in adult obesity. Conclusion : We suggest that individuals with obesity should exercise consistently to achieve significant improvements in their health.

Rett syndrome (RTT) is a severe X-linked dominant neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene; MeCP2 regulates the expression of brain-derived neurotrophic factor (BDNF) and increasing BDNF levels ameliorates RTT symptoms. However, the clinical application of BDNF is limited, because of its short half-life and low penetrance across the blood-brain barrier. In this study, we generated BDNF-secreting mesenchymal stem cells (MSCs) from the human umbilical cord cells, using CRISPR-Cas9. We studied the effects of BDNF-MSCs in MECP2 knockout and MECP2-deficient mice. BDNF-MSCs upregulated the expression of BDNF, pAKT, and pERK1/2 and downregulated that of pp38, both in vitro and in vivo. In our in vivo experiments, BDNF-MSCs increased the body and brain weights in mice. BDNF-MSCs increased the neuronal cell numbers in the hippocampus, cortex, and striatum; in addition, they increased the number of synapses. BDNF-MSCs upregulated BDNF and the activity of BDNF downstream effectors, such as pAKT and pERK 1/2; this upregulation was persistent. In conclusion, BDNF-MSCs generated using CRISPR-Cas9 could be a therapeutic strategy for treating RTT.

To investigate the incidence status of lily viruses on Jeju island, lily samples were collected from 2015 to 2018 and examined for virus infection using reverse transcription polymerase chain reaction. Of the viral infections, mixed and single infections were 70.0% and 17.9%, respectively. The incidence of mixed infections was highest for Plantago asiatica mosaic virus (PIAMV) and Lily symptomless virus (LSV) as 43.4% in 2015; PlAMV, LSV 33.1% in 2016; LSV, Lily mottle virus (LMoV) 10.2% in 2017; and PlAMV, LSV, LMoV and Cucumber mosaic virus (CMV) 15.8% in 2018. The incidence of PlAMV was observed to be 82.0% in 2015, 49.4% in 2016, 13.6% in 2017, and 39.5% in 2018 after the first occurrence of PlAMV in 2013. No symptoms were observed for single infection with LSV. However, in the case of mixed infection with LSV and LMoV, mosaic and leaf malformation symptoms appeared. With mixed infection with LSV and CMV, pale brown necrotic spots appeared, and mosaic and leaf curling were induced. PlAMV was more common in mixed infection than in single infection, and caused necrosis following the development of reddish-brown spots. PlAMV significantly decreased the marketability of lilies owing to the generation of leaf anomalies and curls, and its symptoms were more severe in mixed infections.

Abstract Background To compare clinical characteristics according to the laterality of objective ocular torsion in patients with unilateral superior oblique palsy (SOP). Methods This retrospective study included all patients with a diagnosis of unilateral SOP. They were classified into subgroups according to correspondence between the paretic eye and the extorted eye using fundus photography. Ocular alignment and muscle action were tested by the prism and alternate cover tests and 4-scale movement measure. Various clinical factors, including the amount of preoperative ocular torsion and change in ocular torsion postoperative, were compared between the accordance and disaccordance groups. Results A total of 70 Asian patients (140 eyes) were included and underwent fundus photography preoperatively. Excyclotorsion in the paretic eye was defined as accordance (45 patients), excyclotorsion in the nonparetic eye was defined as disaccordance (25 patients). The presence of horizontal strabismus was detected in 28 (62%) patients in the accordance group and only 8 (32%) patients in the disaccordance group (p = 0.024). All horizontal strabismus observed in the accordance group involved exodeviation. The proportion of horizontal strabismus surgery was also significantly larger in the accordance group than the disaccordance group (p = 0.039). Among those patients, there were 26 who underwent fundus photography postoperatively. There was significant reduction in ocular excyclotorsion postoperatively in the accordance group (p = 0.001), but no significant reduction postoperatively in the disaccordance group (p = 0.270). There was no significant correlation between the amount of torsional reduction and the amount of vertical deviation reduction (p = 0.979). Conclusions In cases of preoperative excyclotorsion in paretic eyes, careful consideration of combined horizontal misalignment which may require surgical correction is helpful to manage unilateral SOP.

Exercise training causes epigenetic changes in skeletal muscle, although it is unclear how resistance exercise (RE) affects histone modifications. The present study was carried out to investigate the effects of acute RE and RE training on gene expression profiles and histone modifications in human skeletal muscle. Healthy male adults were assigned to acute RE (n = 9, age = 20.5±4.3yr, BMI = 28.0±6.8kg/m2) or RE training (n = 21, age = 23.7±2.5yr, BMI = 24.2±2.7kg/m2) groups. Biopsy samples were obtained from the vastus lateralis muscle before and three hours after a single bout of acute RE, or 3-days after 10 weeks of RE training. RNA sequencing analysis revealed that 153 genes with GO terms including muscle development, stress response, metabolism, cell death, and transcription factor were significantly up-regulated (+291% vs. pre-acute RE) upon acute RE. Expressions of these genes were also greater (+9.6% vs. pre-RE training, p

BACKGROUND:Although reversible in some patients, primary hypothyroidism is considered a permanent condition requiring lifelong hormone therapy. This study aimed to investigate the factors predicting the successful discontinuation of levothyroxine (L-T4) therapy in patients with primary hypothyroidism. METHODS:A retrospective study was performed in primary hypothyroidism patients who met inclusion criteria: patients who maintained stable L-T4 therapy for more than 1 year, following gradual dose reduction of L-T4 based on the clinical decision (L-T4 tapering); patients receiving either no L-T4 or a fixed minimum dose for more than 1 year after L-T4 tapering. Reduction in L-T4 dosage by 12.5-50 μg within 3 months was considered as L-T4 tapering. Serum free T4, TSH, and clinical symptoms were evaluated before, during and after tapering. Logistic regression and decision tree analyses were performed to predict the successful discontinuation of L-T4. RESULTS:Among 382 patients, 22.5% and 58.4% showed successful discontinuation (T4-Discontinued) and dose reduction (T4-Reduced) of L-T4 therapy, while other did not obtained any reduction of L-T4 dose (T4-Unchanged). The median number of tapering visit was 1.0 (range, 1.0-4.0). In T4-Discontinued group, the TSH level and the positive rate of anti-thyroperoxidase at the time of L-T4 initiation were lower, the duration of L-T4 therapy was shorter, and the maintenance dose of L-T4 at the time of tapering was lower than those in the T4-Unchanged group. In ultrasonography, normal parenchyma was preserved in the T4-Discontinued group while others showed higher rates of heterogeneous or hypoechoic parenchymal changes. Among those different characteristics, the longer duration of L-T4 therapy and the higher maintenance dose of L-T4 at the time of tapering significantly predicted the failure of discontinuation of L-T4 in multivariate analysis. A decision tree showed that patients with a duration of L-T4 therapy >4.6 years had lower success rate of discontinuation. CONCLUSION:Shorter duration of L-T4 therapy and lower L-T4 dose at the time of tapering are the predictable factors for successful L-T4 tapering in stably maintained primary hypothyroidism patients.

Summary: The resolution phase of acute inflammation is essential for tissue homeostasis, yet the underlying mechanisms remain unclear. We demonstrate that resolution of inflammation involves interactions between CD38 and tristetraprolin (TTP). During the onset of acute inflammation, CD38 levels are increased, leading to the production of Ca2+-signaling messengers, nicotinic acid adenine dinucleotide phosphate (NAADP), ADP ribose (ADPR), and cyclic ADPR (cADPR) from NAD(P)+. To initiate the onset of resolution, TTP expression is increased by the second messengers, NAADP and cADPR, which downregulate CD38 expression. The activation of TTP by Sirt1-dependent deacetylation, in response to increased NAD+ levels, suppresses the acute inflammatory response and decreases Rheb expression, inhibits mTORC1, and induces autophagolysosomes for bacterial clearance. TTP may represent a mechanistic target of anti-inflammatory agents, such as carbon monoxide. TTP mediates crosstalk between acute inflammation and autophagic clearance of bacteria from damaged tissue in the resolution of inflammation during sepsis. : Sepsis as a clinical syndrome is characterized by systemic inflammation and widespread tissue injury. Joe et al. suggest that the activation of TTP, an RNA binding protein, helps to ameliorate the inflammatory response and promote bacterial clearance in sepsis. Keywords: acute inflammation, autophagolysosome, CD38, Rheb, resolution of inflammation, sepsis, Sirt1, tristetraprolin

More than 80% of colorectal cancer patients have adenomatous polyposis coli (APC) mutations, which induce abnormal WNT/β-catenin activation. Tankyrase (TNKS) mediates the release of active β-catenin, which occurs regardless of the ligand that translocates into the nucleus by AXIN degradation via the ubiquitin-proteasome pathway. Therefore, TNKS inhibition has emerged as an attractive strategy for cancer therapy. In this study, we identified pyridine derivatives by evaluating in vitro TNKS enzyme activity and investigated N-([1,2,4]triazolo[4,3-a]pyridin-3-yl)-1-(2-cyanophenyl)piperidine-4-carboxamide (TI-12403) as a novel TNKS inhibitor. TI-12403 stabilized AXIN2, reduced active β-catenin, and downregulated β-catenin target genes in COLO320DM and DLD-1 cells. The antitumor activities of TI-12403 were confirmed by the viability of the colorectal cancer cells and its lack of visible toxicity in DLD-1 xenograft mouse model. In addition, combined 5-FU and TI-12403 treatment synergistically inhibited proliferation to a greater extent than that in a single drug treatment. Our observations suggest that TI-12403, a novel selective TNKS1 inhibitor, may be a suitable compound for anticancer drug development.

Purpose: Predicting neurologic prognosis in pediatric patients recovered after cardiac arrest is more difficult than in adults. This study hypothesized that a combination model of early electroencephalography, brain computed tomography (CT), and laboratory findings improve prediction performance of neurologic outcome in pediatric patients after cardiac arrest.Methods: We retrospectively analyzed the medical records of pediatric patients resuscitated after non-traumatic cardiac arrest. Clinical features, electroencephalography, gray matter to white matter attenuation ratio on brain CT, and laboratory findings were analyzed. The primary outcome was neurologic prognosis based on the Pediatric Cerebral Performance Category score.Results: Of 21 patients, seven (33.3%) were classified as a good neurologic outcome group and 14 (66.7%) were classified as a poor neurologic outcome group. The good outcome group was associated with a slow and disorganized electroencephalographic background pattern (P = 0.006), reactivity (P = 0.006), and electrographic seizures (P = 0.03). The frequency of a suppressed electroencephalographic background pattern was significantly higher in the poor outcome group (P = 0.006). The poor outcome group was also associated with a low level of gray matter to white matter attenuation ratio (P = 0.03) and hyperammonemia (P = 0.003). The area under curve of the combined model, consisting of electroencephalographic background, gray matter to white matter attenuation ratio, and ammonia was the highest at 0.959 (0.772–0.999) with a specificity of 100%.Conclusion: Unfavorable electroencephalographic background, low gray matter to white matter attenuation ratio on brain CT, and hyperammonemia are associated with poor neurologic outcome in children after cardiac arrest.

The development of successful scaffolds for bone tissue engineering requires concurrent engineering that combines different research fields. In previous studies, phenomenological computational models predicted the mechanical properties of a scaffold in a simple loading condition using the mechano-regulation theory. Therefore, the aim of this study is to predict the mechanical properties of an optimum scaffold required for cartilage regeneration using three-dimensional knee joint developed from medical imaging and mechano-regulation theory. It was predicted that the scaffold with optimal mechanical properties would result in greater amounts of cartilage tissue formation than without a scaffold. The results demonstrated the ability of the algorithms to design optimized scaffolds with target properties and confirmed the applicability of set techniques for bone tissue engineering. The scaffolds were optimized to suit the site-specific loading requirements, and the results reveal a new approach for computational simulations in tissue engineering.

PurposeTo compare biometry and prediction of postoperative refractive outcomes obtained by two swept-source optical coherence tomography (SS-OCT) biometers (IOLMaster 700 and Argos), and a partial coherence interferometry (IOLMaster ver 5.4).MethodsBiometric values were measured using two SS-OCT and PCI device and evaluated against one another. Predictive errors were compared at one month after cataract surgery.ResultsOne hundred forty six eyes were considered. Axial length (AXL) measurements were not successful in 3 eyes measured by IOLMaster 700 and Argos devices, and in 17 eyes measured by IOLMaster ver. 5.4 devices. AXL as measured by Argos showed a tendency to be shorter in long eyes with AXL more than 26.0 mm (p < .001) and to be longer in short eyes with AXL less than 22.5 mm (p = .005). Anterior chamber depth as measured by IOLMaster ver. 5.4 was longer than that measured by the other two SS-OCT devices (vs. IOLMaster 700: p = .003; vs. Argos: p = .006). White-to-white diameter measured using Argos was significantly different measurements obtained using two IOLMaster (p < .001, respectively). The mean absolute postoperative prediction errors were 0.41 ± 0.31 diopters (D), 0.42 ± 0.32 D, and 0.35 ± 0.30 D for IOLMaster ver. 5.4, IOLMaster 700, and Argos, respectively.ConclusionThe ocular biometric measurements using three devices showed high agreement. AXL measured by Argos showed a significant difference compared with the measurements from two IOLMaster. ACD was highly correlated between two SS-OCT devices except IOLMaster ver 5.4. LT and CCT values between IOLMaster 700 and Argos were different significantly. SS-OCT devices demonstrated a superior ability to successfully perform measurements compared with PCI device.

Internal tandem duplication (ITD) of FMS-like tyrosine kinase 3 (FLT3) is the most common mutation in patients with acute myeloid leukemia (AML). FLT3-ITD+ induces constitutive activation of FLT3, causing an abnormally rapid proliferation of cancer cells. In this study, we identified novel FLT3 inhibitors and investigated 5-(4-fluorophenyl)-N-phenyloxazol-2-amine (compound 7; 7c) as candidates for the treatment of AML. The results showed that 7c inhibited the activities of FLT3 and mutated FLT3 in a cell-free kinase assay and Molm-13 and MV4-11 cells, as well as the proliferation of FLT3-ITD+ AML cells, increasing apoptosis. The anti-leukemic activity of 7c was confirmed by in vivo tumor growth inhibition in MV4-11 xenograft mice. Besides, 7c suppressed the expression of DNA damage repair genes. Combination treatment with 7c and olaparib (a poly (ADP-ribose) polymerase [PARP] inhibitor) synergistically inhibited cell proliferation in Molm-13 and MV4-11 cells. Our findings demonstrated that 7c is a therapeutic candidate targeting FLT3 for AML treatment and suggested that combination treatment with 7c and a PARP inhibitor may be an effective therapy regimen for FLT3-mutated AML.

The precise regulation of osteoclast differentiation and function is crucial for the maintenance of healthy bone. Despite several reports of collagenase expression in bone tissues, the precise isoform expression as well as the role in osteoclasts are still unclear. In the present report, the expression of matrix metalloprotease (MMP)8 and MMP13 was confirmed in mouse bone marrow macrophage osteoclast precursors. The mRNA and protein expressions of both collagenases were significantly reduced by receptor activator of nuclear factor κB ligand (RANKL) stimulation. Notably, either inhibition of MMP expression by siRNA or treatment of cells with collagenase inhibitor Ro 32-3555 significantly augmented osteoclast fusion and resorption activity without affecting the osteoclast number. The inhibition of collagenase by Ro 32-3555 increased the expression of osteoclast fusion genes, Atp6v0d2 and Dcstamp, without affecting nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) protein expression. The enhanced osteoclast fusion by collagenase inhibition appears to be mediated through an extracellular signal regulated kinase (ERK)-dependent pathway. Collectively, these data provide novel information on the regulation of osteoclast fusion process.

Non-thermal plasma (NTP) has been studied as a novel therapeutic tool for cancer that does not damage healthy cells. In this study, we show that NTP-treated solutions (NTS) can induce death in various leukemia cells through mechanistic target of rapamycin (mTOR) ubiquitination. Previously, we manufactured and demonstrated the efficacy of NTS in solid cancers. NTS did not exhibit any deleterious side effects, such as acute death or weight loss in nude mice. In the present study, NTS induced cell death in myeloid leukemia cells, including acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). We found that mTOR was downregulated in NTS-treated cells via the ubiquitin-proteasome system (UPS). We also identified ‘really interesting new gene’ finger protein 126 (RNF126) as a novel binding protein for mTOR through protein arrays and determined the role of E3 ligase in NTS-induced mTOR ubiquitination. NTS-derived reactive oxygen species (ROS) affected RNF126 expression and lysosomal dysfunction. These findings suggest that NTS has potential antileukemic effects through RNF126-mediated mTOR ubiquitination with no deleterious side effects. Thus, NTS may represent a new therapeutic method for chemotherapy-resistant leukemia.

Due to the rapid advent in genomics technologies and attention to ecological risk assessment, the term “ecotoxicogenomics” has recently emerged to describe integration of omics studies (i.e., transcriptomics, proteomics, metabolomics, and epigenomics) into ecotoxicological fields. Ecotoxicogenomics is defined as study of an entire set of genes or proteins expression in ecological organisms to provide insight on environmental toxicity, offering benefit in ecological risk assessment. Indeed, Daphnia is a model species to study aquatic environmental toxicity designated in the Organization for Economic Co-operation and Development’s toxicity test guideline and to investigate expression patterns using ecotoxicology-oriented genomics tools. Our main purpose is to demonstrate the potential utility of gene expression profiling in ecotoxicology by identifying novel biomarkers and relevant modes of toxicity in Daphnia magna. These approaches enable us to address adverse phenotypic outcomes linked to particular gene function(s) and mechanistic understanding of aquatic ecotoxicology as well as exploration of useful biomarkers. Furthermore, key challenges that currently face aquatic ecotoxicology (e.g., predicting toxicant responses among a broad spectrum of phytogenetic groups, predicting impact of temporal exposure on toxicant responses) necessitate the parallel use of other model organisms, both aquatic and terrestrial. By investigating gene expression profiling in an environmentally important organism, this provides viable support for the utility of ecotoxicogenomics.

Bickerstaff's brainstem encephalitis is characterized by ophthalmoplegia, ataxia, and disturbance of consciousness. It is similar to Miller Fisher syndrome, a variant of Guillain-Barre syndrome, in that they share features such as ophthalmoplegia and ataxia. The difference is that patients with Bickerstaff's brainstem encephalitis have impaired consciousness, whereas patients with Miller Fisher syndrome have alert consciousness and areflexia. Here, we report the case of a 3-year-old child who was diagnosed with Bickerstaff's brainstem encephalitis presenting typical clinical features and interesting radiological findings. The patient showed ophthalmoplegia, ataxia, and subsequent stuporous mentality. Brain magnetic resonance imaging revealed high signal intensity in the pons and cerebellum around the 4th ventricle on a T2-weighted image. He was successfully treated with intravenous immunoglobulin. Differentiation of Bickerstaff's brainstem encephalitis and Miller Fisher syndrome is often difficult because they possess many overlapping features. Brain magnetic resonance imaging may be helpful in diagnosing Bickerstaff's brainstem encephalitis, especially when lesions are definitely found.

[This corrects the article DOI: 10.1371/journal.pone.0166044.].

PurposeAmong the many factors associated with acute intestinal mucosal infection, numerous studies have proposed the usefulness of fecal calprotectin. The aim of this study was to evaluate the usefulness of fecal calprotectin in the diagnosis of necrotizing enterocolitis (NEC).MethodsWe collected 154 stool samples from 16 very low birth weight and premature newborns at the Konyang University Hospital neonatal intensive care unit or neonatal nursery. The stool samples were collected using the Calprest device, and the fecal calprotectin level was measured with the BÜHLMANN Calprotectin enzyme-linked immunosorbent assay kit.ResultsFecal calprotectin levels were significantly higher in the NEC group than in the non-NEC group (P=0.02). There was a significant positive linear relationship between the fecal calprotectin level and number of days after birth (P=0.00) in the gestational age