The effect of the national scaling program on tooth loss: a claim-based matched large cohort study in Korea.

OBJECTIVE: Tooth loss affects quality of life. Scaling is a measure to prevent periodontal disease and tooth loss. This study aimed to determine the effect of scaling on tooth loss. BASIC RESEARCH DESIGN: Secondary analysis of the Korean National Health Insurance Services database, comprising 514,866 Koreans as an initial cohort, followed for 14 years up to 2015. The study population comprised people who had received an oral check-up in 2002-2003. Using propensity score matching, we matched the intervention group (receipt of scaling) and controls (no scaling) 1:1. The outcome, tooth loss was defined as including all teeth except for third molars until 2015. The final sample included 94,738 people. Analysis used a Cox proportional hazard regression model. RESULTS: Scaling showed conflicting results in univariate and multivariable analyses. In univariate analysis, people who received scaling were more likely to lose teeth (HR, 1.04; 95% CI, 1.02-1.05). After adjusting for confounders in the multivariable analysis, those who didn't receive scaling were more likely to lose teeth (HR, 0.97; 95% CI, 0.95, 0.99). The effects of scaling were identified in people without diabetes (HR, 0.97; 95% CI, 0.95, 0.99) but not in people with diabetes (HR, 0.97; 95% CI, 0.89-1.06). CONCLUSIONS: Scaling was associated with less tooth loss. Regular scaling might be encouraged for vulnerable groups, such as males, older adults, lower income, handicapped, chronic diseases, and smokers.

FoxO1 as a Regulator of Aquaporin 5 Expression in the Salivary Gland.

Forkhead box O1 (FoxO1) is a multifunctional initiator, mediator, and repressor of autoimmune diseases in an organ- or disease-specific manner. However, the role of FoxO1 in the salivary gland has not yet been elucidated. In this study, we discovered that FoxO1 and aquaporin 5 (AQP5) are both significantly downregulated in the patients with primary Sjögren syndrome, an autoimmune disease accompanying salivary gland dysfunction. Pharmacologic or genetic perturbation of FoxO1 in the rat salivary gland acinar cell line, SMG-C6, induced a significant downregulation of AQP5 expression, as observed in clinical specimens. There was a strong correlation between FoxO1 and AQP5 expression because FoxO1 is a direct regulator of AQP5 expression in salivary gland acinar cells through its interaction with the promoter region of AQP5. Serial injection of a FoxO1 inhibitor into mice induced a reduction of AQP5 expression in submandibular glands and, consequently, hyposalivation, which is one of the major clinical symptoms of primary Sjögren syndrome. However, there was no sign of inflammation or cell damage in the submandibular glands harvested from mice treated with the FoxO1 inhibitor. In conclusion, our findings indicate that FoxO1 in salivary gland tissue acts as a direct regulator of AQP5 expression. Thus, downregulation of FoxO1 observed in primary Sjögren syndrome is a putative mechanism for hyposalivation without the involvement of previously reported soluble factors in primary Sjögren syndrome patient sera.

Identification of predictive variables for the recurrence of oral mucocele.

BACKGROUND: Oral mucocele is the most common minor salivary gland lesion with good prognosis after surgical removal. However, its recurrence is not rare, sometimes bothersome. This study aimed to identify the possible predictive variables affecting the recurrence rate of oral mucocele. MATERIAL AND METHODS: The histoclinical data of 164 patients diagnosed with oral mucocele were retrospectively obtained by reviewing dental records. The predictive variables for its recurrence were identified by analyzing its recurrence rate according to clinical variables. RESULTS: The recurrence rate showed the significant differences according to location and age. Oral mucocele recurred with significantly higher frequency on the ventral mucosa of tongue (50.0%) than on the labial/buccal mucosa (8.8%). Its recurrence was significantly more common in the younger patients (aged < 30 years, 16.0%) than in the older patients (aged > 30 years, 4.4%). However, there was no significant difference in recurrence rates between surgical procedures using scalpels and those using lasers. CONCLUSIONS: Patients with oral mucocele should be more carefully informed of its possible recurrence, especially when it is found on the ventral surface of the tongue or in a younger population.

Safety and effectiveness of amoxicillin in the treatment of inflammatory acne.

Acne is a common skin disease that predominantly affects teenagers and young adults. Systemic antibiotic therapy, including tetracyclines, macrolides, and trimethoprim-sulfamethoxazole, is indicated in moderate-to-severe inflammatory disease. However, in certain cases, these antibiotics and other commonly prescribed treatments including oral contraceptives, spironolactone, and isotretinoin may be prohibited, especially in cases of pregnancy and drug intolerance. In this retrospective study, we assessed the safety and efficacy of systemic amoxicillin, which has a favorable tolerability profile and compatibility with pregnancy in the treatment of inflammatory acne.

Appropriate non-carbapenems are not inferior to carbapenems as initial empirical therapy for bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a propensity score weighted multicenter cohort study.

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

Spironolactone for the treatment of acne in women, a retrospective study of 110 patients.

BACKGROUND: There is limited evidence on the safety and efficacy of spironolactone in the treatment of women with acne. Thus, for many dermatologists spironolactone remains an alternative rather than a mainstay treatment for female patients with acne. METHODS: An electronic medical records search tool was used to select data from a group of women who received spironolactone to treat acne and were evaluated with the comprehensive acne severity scale (CASS) before treatment and at all follow-up visits. Data points were collected for CASS scores at each follow-up visit, concurrent and previous treatments, and side effects. These data points were used to draw conclusions about the safety and efficacy of spironolactone in this patient population. RESULTS: There were 110 patients that met all eligibility requirements. Of these, 94 patients saw an improvement in their CASS score and 61 patients completely cleared their score to 0. There were 16 patients who did not improve and six who relapsed after initial improvement. The women saw an average improvement in their acne by 73.1% for the face, 75.9% for the chest, and 77.6% for the back. Fifty-one women experienced side effects, but only six found them bothersome enough to stop taking spironolactone. CONCLUSION: A majority of women in this study saw a dramatic improvement in their acne while treated with spironolactone. There were low rates of relapse or discontinuation of the medication. To further promote the use of spironolactone as a first-line systemic treatment for women with acne, there must be more prospective controlled trials.

Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-ß-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems.

Despite a significant increase of bloodstream infection caused by extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems. According to the appropriateness of empiric therapy, individuals were divided into an appropriate empiric therapy (AT) group (n = 106) and IAT group (n = 143). Patients who received AT showed more severe underlying conditions including underlying solid cancer, healthcare-association and intensive care unit (ICU) care, compared to the IAT group. Primary bacteremia was more commonly found in the AT group than in the IAT group, while urinary tract infection predominated more frequently in the IAT group than in the AT group. Multivariate analysis using propensity score analysis indicated that inappropriateness of empiric therapy was not an independent risk factor for 30-day death. ICU care, respiratory tract infection and underlying liver, renal and connective tissue diseases were significantly associated with mortality. In patients with bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae in the community-setting, delay in appropriate therapy was not associated with an increased rate of death if the patients were definitively treated with carbapenems.

The reliability of the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) among dermatologists, rheumatologists and neurologists.

BACKGROUND: Previous studies have shown that skin disease in dermatomyositis (DM) is best assessed using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). Although the CDASI has been validated for use by dermatologists, it has not been validated for use by other physicians such as rheumatologists and neurologists, who also manage patients with DM and assess skin activity in clinical trials. OBJECTIVES: To assess the reliability of the CDASI among dermatologists, rheumatologists and neurologists. METHODS: Fifteen patients with cutaneous DM were assessed using the CDASI and the Physician Global Assessment (PGA) by five dermatologists, five rheumatologists and five neurologists. RESULTS: The mean CDASI activity scores for dermatologists, rheumatologists and neurologists were 21·0, 21·8 and 20·8, respectively. These mean scores were not different among the specialists. The CDASI damage score means for dermatologists, rheumatologists and neurologists were 5·3, 7·0 and 4·8, respectively. The mean scores between dermatologists and rheumatologists were significantly different, but the means between dermatologists and neurologists were not. The intraclass correlation coefficients (ICCs) for interrater reliability for CDASI activity and damage were good to excellent for dermatologists and rheumatologists, and moderate to excellent for neurologists. The ICCs for intrarater reliability for CDASI activity and damage were excellent for dermatologists and rheumatologists and moderate to excellent for neurologists. The PGA displayed lower interrater and intrarater reliability relative to the CDASI. CONCLUSIONS: Our results confirm the reliability of the CDASI when used by dermatologists and rheumatologists. The data for its use by neurologists were not as robust.

Surveillance of the Middle East respiratory syndrome (MERS) coronavirus (CoV) infection in healthcare workers after contact with confirmed MERS patients: incidence and risk factors of MERS-CoV seropositivity.

Given the mode of transmission of Middle East respiratory syndrome (MERS), healthcare workers (HCWs) in contact with MERS patients are expected to be at risk of MERS infections. We evaluated the prevalence of MERS coronavirus (CoV) immunoglobulin (Ig) G in HCWs exposed to MERS patients and calculated the incidence of MERS-affected cases in HCWs. We enrolled HCWs from hospitals where confirmed MERS patients had visited. Serum was collected 4 to 6 weeks after the last contact with a confirmed MERS patient. We performed an enzyme-linked immunosorbent assay (ELISA) to screen for the presence of MERS-CoV IgG and an indirect immunofluorescence test (IIFT) to confirm MERS-CoV IgG. We used a questionnaire to collect information regarding the exposure. We calculated the incidence of MERS-affected cases by dividing the sum of PCR-confirmed and serology-confirmed cases by the number of exposed HCWs in participating hospitals. In total, 1169 HCWs in 31 hospitals had contact with 114 MERS patients, and among the HCWs, 15 were PCR-confirmed MERS cases in study hospitals. Serologic analysis was performed for 737 participants. ELISA was positive in five participants and borderline for seven. IIFT was positive for two (0.3%) of these 12 participants. Among the participants who did not use appropriate personal protective equipment (PPE), seropositivity was 0.7% (2/294) compared to 0% (0/443) in cases with appropriate PPE use. The incidence of MERS infection in HCWs was 1.5% (17/1169). The seroprevalence of MERS-CoV IgG among HCWs was higher among participants who did not use appropriate PPE.

PARP1 enhances lung adenocarcinoma metastasis by novel mechanisms independent of DNA repair.

The role of poly (ADP-ribose) polymerase 1 (PARP1) in cancer has been extensively studied in the context of DNA repair, leading to clinical trials of PARP1 inhibitors in cancers defective in homologous recombination. However, the DNA repair-independent roles of PARP1 in carcinogenesis and metastasis, particularly in lung cancer metastasis, remain largely uncharacterized. Here, we report that PARP1 promotes lung adenocarcinoma relapse to the brain and bones by regulating several steps of the metastatic process in a DNA repair-independent manner. We find that PARP1 expression is associated with overall and distant metastasis-free survival in lung adenocarcinoma patients. Consistent with this, genetic knockdown and pharmacological inhibition of PARP1 significantly attenuated the metastatic potential of lung adenocarcinoma cells. Further investigation revealed that PARP1 potentiates lung adenocarcinoma metastasis by promoting invasion, anoikis resistance, extravasation and self-renewal of lung adenocarcinoma cells and also by modifying the brain microenvironment. Finally, we identified S100A4 and CLDN7 as novel transcriptional targets and clinically relevant effectors of PARP1. Collectively, our study not only revealed previously unknown functions of PARP1 in lung adenocarcinoma metastasis but also delineated the molecular mechanisms underlying the pro-metastatic function of PARP1. Furthermore, these findings provide a foundation for the potential use of PARP1 inhibitors as a new treatment option for lung adenocarcinoma patients with elevated PARP1 expression.

Diagnostic profiling of salivary exosomal microRNAs in oral lichen planus patients.

OBJECTIVE: Oral lichen planus is a chronic inflammatory oral mucosal disease whose exact cause is unclear and which requires efficient diagnostic and therapeutic strategies. Identification of disease-specific biomarkers in saliva is an easy, quick, and non-invasive approach for molecular diagnosis. This study was designed to examine salivary exosomal microRNAs (miRNAs) that could be candidates for diagnosing and elucidating the pathogenesis of oral lichen planus. SUBJECTS AND METHODS: We compared miRNA profiles of salivary exosomes of patients with oral lichen planus with those of healthy controls. Saliva samples from 16 patients with oral lichen planus and eight healthy controls were divided into two sets and examined using miRNA microarray analysis and TaqMan quantitative PCR. RESULTS: The three miRNAs identified (miR-4484, miR-1246, and miR-1290) were further validated. Of these, miR-4484 was significantly upregulated in the salivary exosomes of patients with oral lichen planus. CONCLUSIONS: This study thus identifies a potential miRNA biomarker for oral lichen planus and provides insight into the functions of miRNAs in the pathogenesis of oral inflammatory diseases.

Tuberculosis before hematopoietic stem cell transplantation in patients with hematologic diseases: report of a single-center experience.

BACKGROUND: Few reports discuss the optimal management of patients diagnosed with tuberculosis (TB) before scheduled stem cell transplantation (SCT), who then proceed with transplantation. METHODS: We found 13 patients with TB before SCT (proven, n = 9; probable, n = 3; possible, n = 1) in the medical records of our institution. RESULTS: Most of the patients had pulmonary TB (n = 8; disseminated, n = 2; extrapulmonary, n = 3). Eight of 9 patients with proven disease had SCT after at least 100 days of anti-tuberculous medication, ranging from 103 to 450 days. None of those patients suffered TB-related events after SCT. However, 1 patient with proven pulmonary TB who underwent SCT after only 40 days of anti-tuberculous therapy subsequently died of TB meningitis. Patients with possible and probable disease had their transplants after 6-176 days of anti-tuberculous medication, and all were alive at the time of analysis. The entire duration of anti-tuberculous medication was 12 months in most cases. With a follow-up duration ranging from 0.7 to 87.5 months, 4 patients died, but TB was the cause of death in only 1 case. CONCLUSION: In conclusion, for proven cases of TB, SCT after >100 days of anti-tuberculous medication is probably feasible and safe, in terms of TB control, in patients with various hematologic diseases.

First Report of Powdery Mildew Caused by Golovinomyces sonchicola on Ixeris chinensis in Korea.

Ixeris chinensis (Thunb.) Nakai, known as Chinese ixeris, is distributed from Siberia to Japan, including Korea, Taiwan, and China. The whole plant has been used in folk medicine in Asia (4). In Korea, the plants of Chinese ixeris have been gathered and used as a wild root vegetable. During summer to autumn of 2011, Chinese ixeris leaves were found to be heavily infected with a powdery mildew in several locations of Korea. Symptoms first appeared as thin white colonies, which subsequently developed into abundant hyphal growth on both sides of the leaves, leading to drying of the leaves. The same symptoms on Chinese ixeris leaves were continuously observed in 2012 and 2013. Voucher specimens (n = 10) were deposited at Korea University Herbarium (KUS). Hyphal appressoria were moderately lobed or nipple-shaped. Conidiophores arose from the lateral part of the hyphae, measured 100 to 270 × 10 to 12.5 µm, and produced 2 to 6 immature conidia in chains with a sinuate outline. Basal parts of foot-cells in conidiophores were curved. Conidia were barrel-shaped to ellipsoid, measured 26 to 36 × 13 to 19 µm (length/width ratio = 1.7 to 2.4), lacked fibrosin bodies, and showed reticulate wrinkling of the outer walls. Primary conidia were ovate with conical-obtuse apex and subtruncate base. Germ tubes were produced on the perihilar position of conidia. Chasmothecia were not observed. The morphological characteristics were typical of the Euoidium type anamorph of the genus Golovinomyces, and the fungus measurements and structures were consistent with those of G. sonchicola U. Braun & R.T.A. Cook (1). To confirm the identification, internal transcribed spacer (ITS) region of rDNA sequences from a representative material (KUS-F26212) was amplified using primers ITS5/P3 and sequenced (3). The resulting 416-bp sequence was deposited in GenBank (Accession No. KF819857). A GenBank BLAST search revealed that the isolate showed >99% sequence similarity with those of G. cichoracearum from Sonchus spp. (e.g., AB453762, AF011296, JQ010848, etc.). G. sonchicola is currently confined to G. cichoracearum s. lat. on Sonchus spp., based on molecular sequence analyses (1). Pathogenicity was confirmed through inoculation by gently pressing a diseased leaf onto leaves of five healthy potted Chinese ixeris. Five non-inoculated plants served as controls. Inoculated plants developed symptoms after 6 days, whereas the controls remained symptomless. The fungus present on the inoculated plants was identical morphologically to that originally observed on diseased plants. Powdery mildew infections of I. chinensis associated with Golovinomyces have been known in China (2). To our knowledge, this is the first report of powdery mildew disease caused by G. sonchicola on I. chinensis in Korea. Farming of Chinese ixeris has recently started on a commercial scale in Korea. Though no statistical data are available, we postulate the cultivation area in Korea to be approximately 200 ha, mostly growing without chemical controls. Occurrence of powdery mildews poses a potential threat to safe production of this vegetable, especially in organic farming. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (2) F. L. Tai. Bull. Chinese Bot. Sci. 2:16, 1936. (3) S. Takamatsu et al. Mycol. Res. 113:117, 2009. (4) S. J. Zhang et al. J. Nat. Prod. 69:1425, 2006.

First Report of Powdery Mildew Caused by Golovinomyces artemisiae on Artemisia annua in Korea.

Artemisia annua L., known as sweet wormwood or sweet annie, is native to temperate Asia, but is naturalized throughout the world. It produces artemisinin, a potent antimalarial drug that is also effective in treating other parasitic diseases (4). In August 2013, hundreds of plants showing typical symptoms of powdery mildew were found in Seoul (37°36'29.4″ N 127°02'38.3″ E), Korea. Powdery mildew colonies first appeared as thin white patches, which progressed to abundant hyphal growth on both sides of the leaves, stems, and inflorescence. As symptoms continued to develop, the leaves became distorted and turned purplish-gray. Severe infections caused leaf withering and premature senescence. The same symptoms were found on sweet wormwoods in Nonsan (36°09'55.3″ N 127°01'07.1″ E) and Chuncheon (37°52'27.4″ N 127°43'10.0″ E), Korea. Voucher specimens were deposited in the Korea University Herbarium (KUS). Appressoria on the mycelium were nipple-shaped or occasionally lobed. Conidiophores were cylindrical, measured 120 to 230 × 10 to 12.5 µm, and produced 2 to 4 immature conidia in chains with a sinuate outline, followed by 2 to 3 cells. Foot-cells of conidiophores were straight, cylindrical, and 54 to 100 µm long. Conidia were hyaline, ellipsoid to barrel-shaped, measured 30 to 40 × 15 to 20 µm (length/width ratio of 1.5 to 2.1), lacked distinct fibrosin bodies, and showed reticulate wrinkling of the outer walls. Germ tubes were produced on the perihilar position of conidia. Primary conidia were apically rounded, basally subtruncate, and generally smaller than the secondary conidia. No chasmothecia were observed. The structures described above were typical of the powdery mildew Euoidium anamorph of the genus Golovinomyces, and the fungus measurements were similar to those of G. artemisiae (Grev.) V.P. Heluta (3). The complete internal transcribed spacer (ITS) region of rDNA from KUS-F27763 was amplified with primers ITS1/ITS4 and sequenced. The resulting sequence of 624 bp was deposited in GenBank (Accession No. KJ136112). The obtained ITS sequence shared >99% similarity with G. artemisiae on A. princeps and A. montana from Japan (AB077659 and AB077649) and A. argyi from China (KF056818). Pathogenicity was confirmed through inoculation by gently dusting conidia onto leaves of five healthy potted plants. Five non-inoculated plants served as controls. Inoculated plants developed symptoms after 5 days, whereas the control plants remained symptomless. The fungus present on the inoculated plants was identical morphologically to that originally observed on diseased plants. Powdery mildews of A. annua caused by G. artemisiae have been reported in Japan, China, the Russian Far East, and Romania (1,2). To our knowledge, this is the first report of powdery mildew caused by G. artemisiae on A. annua in Korea. Since sweet wormwood production was only recently started on a commercial scale in Korea, powdery mildew infections pose a serious threat to the production of this plant, especially in organic farming where chemical control options are limited. References: (1) K. Amano. Host Range and Geographical Distribution of the Powdery Mildew Fungi. Japan Scientific Societies Press, Tokyo, 1986. (2) U. Braun. The Powdery Mildews (Erysiphales) of Europe. G. Fischer Verlag, Jena, 1995. (3) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (4) P. J. Weathers et al. Phytochem. Rev. 10:173, 2011.

Modelling single- and tandem-bubble dynamics between two parallel plates for biomedical applications.

Carefully timed tandem microbubbles have been shown to produce directional and targeted membrane poration of individual cells in microfluidic systems, which could be of use in ultrasound-mediated drug and gene delivery. This study aims at contributing to the understanding of the mechanisms at play in such an interaction. The dynamics of single and tandem microbubbles between two parallel plates is studied numerically and analytically. Comparisons are then made between the numerical results and the available experimental results. Numerically, assuming a potential flow, a three-dimensional boundary element method (BEM) is used to describe complex bubble deformations, jet formation, and bubble splitting. Analytically, compressibility and viscous boundary layer effects along the channel walls, neglected in the BEM model, are considered while shape of the bubble is not considered. Comparisons show that energy losses modify the bubble dynamics when the two approaches use identical initial conditions. The initial conditions in the boundary element method can be adjusted to recover the bubble period and maximum bubble volume when in an infinite medium. Using the same conditions enables the method to recover the full dynamics of single and tandem bubbles, including large deformations and fast re-entering jet formation. This method can be used as a design tool for future tandem-bubble sonoporation experiments.

Src homology 2-containing protein tyrosine phosphatase-2 acts as a negative regulator for MUC5AC transcription via the inhibition of the ERK1/2 MAPK signalling pathway in the airway.

AIMS: Mucus hypersecretion has been frequently observed in inflammation respiratory diseases. However, the negative regulators for mucus overproduction have not been readily identified. Our work focused on identifying novel negative regulator that modulates mucus overproduction in the human respiratory system. Herein, we examined whether H2 O2 could induce MUC5AC transcription in a dose-dependent manner and activate tyrosine phosphatase (SHP)-2 in human airway epithelial cells. METHODS: We performed qRT-PCR to detect the changes in MUC5AC transcription and dot-blotting analysis to investigate MUC5AC secretion as regulated by SHP-2. RESULTS: H2 O2 induced MUC5AC transcription in a dose-dependent manner and dramatically activated SHP-2. In addition, whereas wild-type SHP-2 completely inhibited H2 O2 -induced MUC5AC transcription, siRNA-SHP-2 restored it interestingly, suggesting that SHP-2 may act as a negative regulator for mucus overproduction and hypersecretion in the human respiratory tract. Moreover, SHP-2 inhibited the ERK1/2 MAPK pathway, thus abolishing the signalling for MUC5AC transcription. CONCLUSION: We found that H2 O2 induced SHP-2 activation, which acted as a suppressor in H2 O2 signalling to regulate MUC5AC transcription in the airway.

First Report of Bacterial Leaf Spot of Witloof, Caused by Pseudomonas cichorii in Korea.

In August 2011, bacterial leaf spot was observed on witloof (Cichorium intybus L. var. foliosum) grown in a commercial field with 15% incidence in Injae, Korea. Symptoms on leaves included irregular brown to reddish brown spots in the center. Bacterial streaming from the lesions was observed microscopically. Bacterial isolates (BC3286, BC3287, and BC3308-BC3310) were recovered on Trypticase soy agar from lesions surface-sterilized in 70% ethyl alcohol for 30 s. The isolates were gram negative, urease negative, fluorescent on King's B agar, and had aerobic rods with 2 to 6 polar flagella. Pathogenicity tests were separately performed in different greenhouses located in Suwon (National Academy of Agricultural Science) and Chuncheon (Gangwondo Agricultural Research and Extension Services) in Korea. Pathogenicity was confirmed by spray inoculation of healthy, 10-day-old leaves of witloof plants (two plants/isolate) with a suspension of original field isolate (106 CFU/ml). Sterile distilled water was used as negative control. The inoculated plants were incubated in a growth chamber (25°C and 95% relative humidity [RH]) overnight, then transferred to a greenhouse at 23 to 27°C and 60 to 70% RH. Characteristic leaf spot symptoms were observed on inoculated witloof plants 8 days after inoculation. No symptoms were observed on control plants. The bacterium reisolated from the inoculated leaves was confirmed by analyzing sequence of the gyrB gene with direct sequencing method of PCR products using primers gyr-F and gyr-R (2). The sequence of reisolated bacteria shared 100% similarity with inoculated ones. In LOPAT (1) tests, all isolates and the reference strain of Pseudomonas cichorii CFBP2101T (=BC2595) were levan negative, oxidase positive, potato rot negative, arginine dihydrolase negative, and tobacco hypersensitivity positive, indicative of group III (-, +, -, -, +) of fluorescent pseudomonads. The 16S rRNA (1,408 bp), and gyrB (676 bp) regions were sequenced to aid in identification of the original field isolates as well as P. cichorii CFBP 2101T (=BC2595) using reported sets of PCR primers, fD1/rP2 and gyr-F/gyr-R, respectively (2,4). Phylogenetic analyses based on partial sequences of the gyrB and the 16S rRNA of Psudomonas spp. available in GenBank, the reference strain of P. cichorii CFBP2101T (=BC2595), and the witloof field isolates were conducted using the neighbor-joining method with Juke-Cantor model of distance calculation in MEGA version 5.1 (3). The isolates and the reference strain of P. cichorii CFBP2101T (=BC2595) was clustered in one group with P. cichorii strains in both phylogenetic trees based on the two sequences. Sequences of the 16S rRNA region had a distance index value ranging from 0.000 to 0.001 between the reference strain of P. cichori CFBP2101T (GenBank JX913784) and the field isolates (JX913785 to JX913789), and ranged from 0.000 to 0.001 within the field isolates. Sequences of the gyrB region had a distance index value ranging 0.029 to 0.033 between the reference strain (JX913790) and the field isolates (JX913791 to JX913795), and ranged from 0.000 to 0.041 within the field isolates. To our knowledge, this is the first report of bacterial leaf spot of witloof caused by P. cihorii in Korea. P. cichorii has a wide host range, and an important economic impact on vegetables. The disease is expected to result in a significant economic impact on root production of witloof in Korea. References: (1) R. A. Lelliott et al. J. Appl. Bacteriol. 29:470, 1966. (2) H. Sawada et al. J. Mol. Evol. 49:627, 1999. (3) K. Tamura et al. Mol. Biol. Evol. 28:2731, 2011. (4) W. G. Weinsburg et al. J. Bacteriol. 173, 697, 1991.

First Report of Powdery Mildew Caused by Erysiphe cruciferarum on Garden Cress in Korea.

Garden cress (Lepidium sativum L.), belonging to the family Brassicaceae, is an edible herb with peppery flavor and aroma (2). This plant was recently introduced and is cultivated as an edible green under organic farming in Korea. In September 2012, seedlings showing typical symptoms of powdery mildew were found in greenhouses in Pyeongchang County, Korea. Symptoms first appeared as thin white colonies, which progressed to abundant growth on the leaves and stems. Infected herbs were unmarketable mainly due to signs of senescence and withering of leaves and mostly abandoned without becoming harvested. Two samples of diseased leaves were deposited in the Korea University Herbarium (KUS Accession Nos. F27137 and F27150). Appressoria on the mycelium were well-developed, lobed, and solitary or in opposite pairs. Conidiophores were unbranched, cylindrical, 88 to 120 × 8.5 to 10 µm, and composed of 3 to 4 cells. Foot-cells of conidiophores were straight to sub-straight, cylindric, 22 to 42 µm long, and generally equal to or shorter than the upper cells. Singly produced conidia were oblong to cylindrical or oval, 34 to 52 × 14 to 18 µm with a length/width ratio of 2.2 to 3.3, with angular/rectangular wrinkling of outer walls, and no distinct fibrosin bodies. Germ tubes were produced on the perihilar position of conidia. No chasmothecia were found. These structures are typical of the powdery mildew Pseudoidium anamorph of the genus Erysiphe. The specific measurements match with those of E. cruciferarum Opiz ex L. Junell as previously described (1). To confirm the identification, the complete internal transcribed spacer (ITS) region of rDNA from KUS-F27150 was amplified with primers ITS5 and P3 and directly sequenced (4). The resulting 554-bp sequence was deposited in GenBank (Accession No. KC414675). The amplified ITS sequence shared >99% similarity with the sequences of E. cruciferarum on several brassicaceous hosts (EU140958, FJ548627, and GU721075). Pathogenicity was confirmed through inoculation by gently dusting conidia onto leaves of five healthy potted garden cress plants. Five non-inoculated plants served as controls. Inoculated plants were isolated from non-inoculated plants in separate rooms in a greenhouse at 18 to 24°C. Inoculated plants developed signs and symptoms after 8 days, whereas the control plants remained symptomless. The fungus present on the inoculated plants was morphologically identical to that originally observed on diseased plants, fulfilling Koch's postulates. Previously, the disease was reported in several European countries and southeastern Asia (Lebanon, Israel, Iran, Iraq, India, and China) (3). To our knowledge, this is the first report of powdery mildew caused by E. cruciferarum on garden cress in Korea. Since garden cress production was only recently started on a commercial scale in Korea, powdery mildew infections pose a serious threat to the production of this herb, especially in organic farming where chemical control options are limited. References: (1) U. Braun and R. T. A. Cook. Taxonomic Manual of the Erysiphales (Powdery Mildews), CBS Biodiversity Series No.11. CBS, Utrecht, 2012. (2) S. Choudhary et al. Indian J. Agric. Sci. 80:752, 2010. (3) D. F. Farr and A. Y. Rossman. Fungal Databases, Syst. Mycol. Microbiol. Lab., Online publication. ARS, USDA. Retrieved December 2, 2012. (4) S. Takamatsu et al. Mycol. Res. 113:117, 2009.

5-HT(1B) receptors inhibit glutamate release from primary afferent terminals in rat medullary dorsal horn neurons.

BACKGROUND AND PURPOSE: Although 5-HT(1B) receptors are expressed in trigeminal sensory neurons, it is still not known whether these receptors can modulate nociceptive transmission from primary afferents onto medullary dorsal horn neurons. EXPERIMENTAL APPROACH: Primary afferent-evoked EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices using a conventional whole-cell patch clamp technique under a voltage-clamp condition. KEY RESULTS: CP93129, a selective 5-HT(1B) receptor agonist, reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, CP93129 reduced the frequency of spontaneous miniature EPSCs without affecting the current amplitude. The CP93129-induced inhibition of EPSCs was significantly occluded by GR55562, a 5-HT(1B/1D) receptor antagonist, but not LY310762, a 5-HT(1D) receptor antagonist. Sumatriptan, an anti-migraine drug, also decreased EPSC amplitude, and this effect was partially blocked by either GR55562 or LY310762. On the other hand, primary afferent-evoked EPSCs were mediated by the Ca(2+) influx passing through both presynaptic N-type and P/Q-type Ca(2+) channels. The CP93129-induced inhibition of EPSCs was significantly occluded by ω-conotoxin GVIA, an N-type Ca(2+) channel blocker. CONCLUSIONS AND IMPLICATIONS: The present results suggest that the activation of presynaptic 5-HT(1B) receptors reduces glutamate release from primary afferent terminals onto medullary dorsal horn neurons, and that 5-HT(1B) receptors could be, at the very least, a potential target for the treatment of pain from orofacial tissues.