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1.
J Hosp Infect ; 146: 93-101, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38369061

ABSTRACT

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are of serious concern worldwide due to high morbidity and mortality. AIM: To evaluate the impact of the result of a subsequent polymerase chain reaction (PCR) test for carbapenemase after serial negative surveillance cultures on positive culture conversion in patients with three consecutive negative surveillance cultures for CPE, and to identify risk factors for conversion. METHODS: A retrospective study of patients with positive CPE cultures on CHROMagar KPC medium was performed in a Korean tertiary hospital from October 2018 to December 2022. PCR for blaKPC, blaNDM, blaIMP, blaVIM, blaGES, and blaOXA-48 was performed after three consecutive negative rectal swab cultures. Clinical characteristics and outcomes of patients were compared according to whether follow-up PCR was positive (CNPP) or negative (CNPN). FINDINGS: Of 1075 patients with positive CPE cultures, 150 (14.0%) yielded three consecutive negative rectal swab cultures. Of these, 50 (33.3%) were CNPP, and 100 (66.7%) were CNPN. Risk factors associated with a positive PCR result on multivariate analysis were: age, central venous catheter, and Escherichia coli infection. CNPP patients were more likely to have positive culture conversion for CPE than CNPN patients (39/44 (88.6%) vs 21/50 (42.0%), P<0.001). In multivariate analysis, independent risk factors for culture conversion were: a positive PCR result after surveillance cultures, diabetes mellitus, central venous catheter, and Klebsiella pneumoniae. CONCLUSION: CNPP patients have higher rates of culture conversion than CNPN patients, and a follow-up PCR test after serial negative surveillance cultures is useful in deciding whether or not to discontinue contact precautions.


Subject(s)
Enterobacteriaceae Infections , Humans , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/epidemiology , Retrospective Studies , beta-Lactamases/genetics , Bacterial Proteins/genetics , Klebsiella pneumoniae , Polymerase Chain Reaction , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use
2.
Eur J Prosthodont Restor Dent ; 30(1): 49-54, 2022 Feb 28.
Article in English | MEDLINE | ID: mdl-33848409

ABSTRACT

Cleft Lip and/or Palate (CLP) is the most common cranio-facial abnormality thought to be caused by a combination of genetic and environmental factors causing challenges with feeding, dental development and speech. Cleft affected individuals often present a unique set of challenges with regards to their oro-facial and dental development and require multidisciplinary care. This article aims to describe the role of the restorative dentist in the multidisciplinary management of cleft affected individuals and outlines the various clinical presentations and restorative challenges. This article describes the various treatment modalities provided for cleft affected individuals under the National Health Service (NHS) at Liverpool University Dental Hospital (LUDH) and ranges from minimally invasive techniques to conventional fixed and removable prosthodontics.


Subject(s)
Cleft Lip , Cleft Palate , Cleft Lip/surgery , Cleft Palate/surgery , Humans , State Medicine
3.
Opt Express ; 29(10): 14682-14693, 2021 May 10.
Article in English | MEDLINE | ID: mdl-33985185

ABSTRACT

We report the theoretical and experimental investigation of a self-starting mode-locked fiber laser with a nanoengineered Tm3+-doped yttrium-alumina-silica (YAS) fiber as the gain medium. The YAS fiber exhibits a higher capability of Tm3+ cluster elimination than commercial silica fibers. The Tm3+ fluorescence properties and YAS dispersion are well characterized. As a result, an efficient picosecond mode-locked fiber laser is demonstrated with a slope efficiency of 14.14% and maximum pulse energy of 1.27 nJ. To the best of our knowledge, this is the first mode-locked fiber laser based on a Tm3+-doped YAS fiber. The experimental observation is also supported by the numerical analysis.

4.
J Eur Acad Dermatol Venereol ; 35(7): 1587-1594, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33721365

ABSTRACT

BACKGROUND: Letibotulinum toxin A (LeBA) was approved by the Ministry of Food and Drug Safety (known as the Korea Food & Drug Administration) for cosmetic indications in 2012. However, the efficacy and safety of this newly introduced LeBA have not been investigated in crow's feet lines (CFL) treatment and standardization before its universal use. OBJECTIVE: The aim of this multicentre, double-blind, randomized, parallel, active-controlled Phase III clinical trial with two stages (ClinicalTrials.gov identifier: NCT03408236) was to investigate the non-inferiority of LeBA vs. the existing onabotulinum toxin A (OnBA) for the treatment of CFL. METHODS: A total of 240 subjects were randomized to either the test (LeBA) or control (OnBA) group. At the baseline and at weeks 4 while maximum smiling (primary efficacy assessment), 8, 12 and 16, investigator's on-site evaluation, independent evaluator, evaluation by the subjects, subjects' satisfaction assessment and safety assessment were performed. RESULTS: At week 4, the response rate of primary efficacy assessment was 69.75% and 68.33% in the test (LeBA) and control (OnBA) groups, respectively, without a significant difference. Other minor secondary evaluation results showed significant differences suggesting that LeBA offered better improvement than OnBA, but the overall results did not show significant differences between the two groups. CONCLUSION: This study showed that LeBA was as effective and safe as OnBA for the treatment of CFL at the same doses.


Subject(s)
Botulinum Toxins, Type A , Neuromuscular Agents , Skin Aging , Botulinum Toxins, Type A/adverse effects , Double-Blind Method , Republic of Korea , Treatment Outcome
5.
Osteoarthritis Cartilage ; 27(12): 1811-1821, 2019 12.
Article in English | MEDLINE | ID: mdl-31536815

ABSTRACT

OBJECTIVE: To explore the effects of Mg2+ on the expression of osteoarthritic markers in human cartilage and synovium tissue explants. To investigate the therapeutic effect of intra-articular injection of Mg2+ in an established rat OA (Osteoarthritis) model of anterior cruciate ligament transection with partial medial meniscectomy (ACLT + PMM). DESIGN: Human cartilage and synovium explants were collected from total knee replacement surgeries and incubated with MgCl2 (20 mmol/L) in vitro. A rat OA model was established by ACLT + PMM surgery in 450-500 g male Sprague Dawley (SD) rats. To select the optimal dose, intra-articular injections of MgCl2 (0.05, 0.5, 5 mol/L) were performed at 4 weeks after the surgery every 3 days for 2 weeks. The effect of optimized MgCl2 was further determined by histology, immunohistochemistry, and quantitative real-time polymerase chain reaction. RESULTS: The expressions of osteoarthritic markers in human cartilage and synovium explants were inhibited by Mg2+in vitro. Immunohistochemical analysis further suggested the inhibitory effects of Mg2+ on the expression of MMP-13 and IL-6 in the human tissue explants. Cartilage degeneration and synovitis in ACLT + PMM rats were significantly improved by intra-articular injections of Mg2+ (0.5 mol/L). Immunohistochemical analysis also showed the regulatory effects of Mg2+ on osteoarthritic markers in both cartilage and synovium in rats, consistent with in vitro results. CONCLUSION: Intra-articular injections of Mg2+ at 0.5 mol/L attenuate the progression of OA in the ACLT + PMM rat model. Such effect was at least in part explained by the promotion of cartilage matrix synthesis and the suppression of synovial inflammation.


Subject(s)
Cartilage, Articular/drug effects , Magnesium Chloride/pharmacology , Matrix Metalloproteinase 13/drug effects , Osteoarthritis, Knee/metabolism , Synovial Membrane/drug effects , Synovitis/metabolism , ADAMTS Proteins/drug effects , ADAMTS Proteins/genetics , ADAMTS Proteins/metabolism , Aged , Aggrecans/drug effects , Aggrecans/genetics , Aggrecans/metabolism , Animals , Anterior Cruciate Ligament/surgery , Arthroplasty, Replacement, Knee , Cartilage, Articular/metabolism , Collagen Type II/drug effects , Collagen Type II/genetics , Collagen Type II/metabolism , Disease Models, Animal , Female , Humans , Immunohistochemistry , In Vitro Techniques , Injections, Intra-Articular , Interleukin-1beta/drug effects , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Male , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Matrix Metalloproteinase 9/drug effects , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Meniscectomy , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Rats , Real-Time Polymerase Chain Reaction , Synovial Membrane/metabolism
6.
Med J Malaysia ; 74(4): 259-265, 2019 08.
Article in English | MEDLINE | ID: mdl-31424030

ABSTRACT

BACKGROUND: Vitamin D deficiency has been shown to be a determinant of disease severity in patients with atopic dermatitis (AD). There is a lack of information on the prevalence of vitamin D deficiency in Malaysian children with AD. The objective of this study was to determine the association of vitamin D deficiency with AD severity, to compare vitamin D deficiency between children with and without AD and to determine prevalence of vitamin D deficiency in children with AD. METHODS: A case-control study to examine serum 25- hydroxyvitamin D [25(OH)D] levels in children with and without AD was done. Serum 25-hydroxyvitamin D [25(OH)D] level was measured by immunoassay. AD severity was evaluated using the SCORing Atopic Dermatitis (SCORAD) index. RESULTS: The serum levels of 25(OH)D, measured in 135 children with AD was not statistically different from 65 children without AD [median (IQR): 25.2ng/mL (15.45) vs 25.9ng/mL (15.87), p=0.616]. However, serum vitamin D levels were significantly lower in children with severe AD compared to those with mild-to-moderate AD [median (IQR): 16.0ng/mL (19.32) vs 26.3ng/mL (15.56), p=0.021]. The odds of having vitamin D deficiency in children with severe AD was 3.82 times that of children with non-severe AD (95% confidence level: 1.13, 12.87). CONCLUSION: This study suggests that there is an inverse association between vitamin D level and the severity of AD in Malaysian children.


Subject(s)
Dermatitis, Atopic/etiology , Vitamin D Deficiency/complications , Vitamin D/analogs & derivatives , Adolescent , Biomarkers/blood , Case-Control Studies , Child , Child, Preschool , Dermatitis, Atopic/diagnosis , Female , Humans , Malaysia , Male , Prevalence , Risk Factors , Severity of Illness Index , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/diagnosis , Vitamin D Deficiency/epidemiology
7.
Br J Dermatol ; 180(5): 1030-1038, 2019 05.
Article in English | MEDLINE | ID: mdl-30623408

ABSTRACT

BACKGROUND: Transient receptor potential vanilloid subfamily, member 1 (TRPV1) may play an important role in pruritus and inflammation induction in atopic dermatitis (AD). The treatment effect of TRPV1 antagonist via topical application in patients with AD remains unknown. OBJECTIVES: To assess the clinical efficacy and safety of PAC-14028, a TRPV1 antagonist, via topical application in patients with AD. METHODS: In this 8-week, phase IIb, randomized, double-blind, multicentre, vehicle-controlled study, patients with mild-to-moderate AD were randomized to receive PAC-14028 cream 0·1%, 0·3%, 1·0% or vehicle cream twice daily. The primary efficacy end point was the Investigator's Global Assessment (IGA) success rate defined as the percentage of patients with an IGA score of 0 or 1 at week 8. The secondary efficacy end points included the severity Scoring of Atopic Dermatitis (SCORAD) index and Eczema Area and Severity Index (EASI) 75/90. RESULTS: A total of 194 patients were enrolled. IGA success rates at week 8 were 14·58% for vehicle cream, 42·55% for PAC-14028 cream 0·1% (P = 0·0025 vs. vehicle), 38·30% for PAC-14028 cream 0·3% (P = 0·0087 vs. vehicle) and 57·45% for PAC-14028 cream 1·0% (P < 0·001 vs. vehicle). In particular, statistically significant differences were found between the vehicle and treatment groups in the IGA success rates with two-grade improvement. The SCORAD index, EASI 75/90, sleep disturbance score and pruritus visual analogue scale showed a trend towards improvement. No significant safety issues were reported. CONCLUSIONS: PAC-14028 cream may be an effective and safe treatment modality for the treatment of patients with mild-to-moderate AD.


Subject(s)
Acrylamides/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Dermatitis, Atopic/drug therapy , Pruritus/drug therapy , Pyridines/administration & dosage , TRPV Cation Channels/antagonists & inhibitors , Acrylamides/adverse effects , Adult , Anti-Inflammatory Agents/adverse effects , Dermatitis, Atopic/complications , Dermatitis, Atopic/diagnosis , Dermatitis, Atopic/immunology , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , Pruritus/diagnosis , Pruritus/immunology , Pyridines/adverse effects , Severity of Illness Index , Skin Cream/administration & dosage , Skin Cream/adverse effects , Treatment Outcome , Visual Analog Scale , Young Adult
8.
Expert Opin Drug Deliv ; 15(9): 905-913, 2018 09.
Article in English | MEDLINE | ID: mdl-30169977

ABSTRACT

INTRODUCTION: Therapeutic gene editing is becoming a viable biomedical tool with the emergence of the CRISPR/Cas9 system. CRISPR-based technologies have promise as a therapeutic platform for many human genetic diseases previously considered untreatable, providing a flexible approach to high-fidelity gene editing. For many diseases, such as sickle-cell disease and beta thalassemia, curative therapy may already be on the horizon, with CRISPR-based clinical trials slated for the next few years. Translation of CRISPR-based therapy to in vivo application however, is no small feat, and major hurdles remain for efficacious use of the CRISPR/Cas9 system in clinical contexts. AREAS COVERED: In this topical review, we highlight recent advances to in vivo delivery of the CRISPR/Cas9 system using various packaging formats, including viral, mRNA, plasmid, and protein-based approaches. We also discuss some of the barriers which have yet to be overcome for successful translation of this technology. EXPERT OPINION: This review focuses on the challenges to efficacy for various delivery formats, with specific emphasis on overcoming these challenges through the development of carrier vehicles for transient approaches to CRISPR/Cas9 delivery in vivo.


Subject(s)
Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Gene Editing/methods , Genetic Therapy/methods , Animals , CRISPR-Cas Systems/genetics , Gene Transfer Techniques , Humans , RNA, Messenger/genetics
9.
Skin Res Technol ; 24(2): 229-234, 2018 May.
Article in English | MEDLINE | ID: mdl-29067709

ABSTRACT

BACKGROUND/PURPOSE: Sensitive skin is characterized by uncomfortable sensations in response to multiple factors that do not normally have irritant properties. We used an epidemiological approach to evaluate the prevalence and characteristics of sensitive skin in a Korean population, and compared the results with those of populations from other countries. METHODS: A representative nationwide sample of 1000 Koreans aged ≥15 years was selected. The methodology used in this study (questionnaires) was the same as that used in similar studies conducted in other countries. RESULTS: Sensitive skin was present in 56.8% of the Koreans. The prevalence of sensitive skin was highest among countries such as the USA (44.6%), Europe (38.4%), Russia (39.7%), Brazil (34.2%), and Japan (54.5%). Participants with sensitive skin were more likely to accompany skin disorders than those with non-sensitive skin (72.3% vs 38.0%; P < .001). Sensitive skin group were 2-3 times more reactive to climatic and environmental factors, cosmetics, and food items than non-sensitive skin group. CONCLUSION: The prevalence of sensitive skin in Korea is the highest among countries in which such investigation has been conducted. The sensitive skin group appears more likely to experience dermatological reactions to unexpected factors than the non-sensitive skin group.


Subject(s)
Skin Diseases/ethnology , Adolescent , Adult , Aged , Climate , Cosmetics/adverse effects , Diet/adverse effects , Environmental Exposure/adverse effects , Female , Humans , Male , Middle Aged , Republic of Korea/epidemiology , Republic of Korea/ethnology , Self Report , Skin Diseases/epidemiology , Young Adult
10.
Skin Res Technol ; 24(1): 16-19, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28543874

ABSTRACT

BACKGROUND/PURPOSE: Hyaluronic acid (HA) is an anionic, non-sulfated glycosaminoglycan distributed throughout the human skin and injectable HA fillers are the most commonly used in aesthetic field. This study aimed to determine if differences in physical characteristics of HA products (monophasic or biphasic fillers) affect the patterns of magnetic resonance imaging (MRI). METHODS: Twenty biphasic fillers and nine monophasic fillers were obtained from a commercial source, and examined with a 3.0 Tesla MRI scanner. Visual assessments and measurements of signal intensity for region of interest (ROI) were performed. A non-parametric Wilcoxon rank sum test was used to compare the ROI values. RESULTS: Visual assessments by a radiologist did not show significant differences between the two types of fillers. While the signal intensity between the two types of filler did not differ significantly for T1-weighted images, the signal intensity of the biphasic filler was lower than that of the monophasic filler for T2-weighted images (P<.01). CONCLUSION: Monophasic and biphasic HA fillers exhibited different MRI properties. Our findings may provide better insights into the use of in vivo MRI to evaluate aesthetic, procedure-related complications.


Subject(s)
Dermal Fillers , Hyaluronic Acid , Magnetic Resonance Imaging/methods , Cosmetic Techniques , Humans , Observer Variation , Reproducibility of Results
11.
Schizophr Res ; 185: 17-32, 2017 07.
Article in English | MEDLINE | ID: mdl-28094170

ABSTRACT

The watershed-hypothesis of schizophrenia asserts that over 200 different mutations dysregulate distinct pathways that converge on an unspecified common mechanism(s) that controls disease ontogeny. Consistent with this hypothesis, our RNA-sequencing of neuron committed cells (NCCs) differentiated from established iPSCs of 4 schizophrenia patients and 4 control subjects uncovered a dysregulated transcriptome of 1349 mRNAs common to all patients. Data reveals a global dysregulation of developmental genome, deconstruction of coordinated mRNA networks, and the formation of aberrant, new coordinated mRNA networks indicating a concerted action of the responsible factor(s). Sequencing of miRNA transcriptomes demonstrated an overexpression of 16 miRNAs and deconstruction of interactive miRNA-mRNA networks in schizophrenia NCCs. ChiPseq revealed that the nuclear (n) form of FGFR1, a pan-ontogenic regulator, is overexpressed in schizophrenia NCCs and overtargets dysregulated mRNA and miRNA genes. The nFGFR1 targeted 54% of all human gene promoters and 84.4% of schizophrenia dysregulated genes. The upregulated genes reside within major developmental pathways that control neurogenesis and neuron formation, whereas downregulated genes are involved in oligodendrogenesis. Our results indicate (i) an early (preneuronal) genomic etiology of schizophrenia, (ii) dysregulated genes and new coordinated gene networks are common to unrelated cases of schizophrenia, (iii) gene dysregulations are accompanied by increased nFGFR1-genome interactions, and (iv) modeling of increased nFGFR1 by an overexpression of a nFGFR1 lead to up or downregulation of selected genes as observed in schizophrenia NCCs. Together our results designate nFGFR1 signaling as a potential common dysregulated mechanism in investigated patients and potential therapeutic target in schizophrenia.


Subject(s)
Gene Expression Regulation, Developmental/genetics , Genome/genetics , Mutation/genetics , Receptor, Fibroblast Growth Factor, Type 1/genetics , Receptor, Fibroblast Growth Factor, Type 1/metabolism , Schizophrenia/genetics , Signal Transduction/genetics , Adult , Cell Differentiation , Cells, Cultured , Female , Gene Regulatory Networks , Genomics , Humans , Induced Pluripotent Stem Cells/physiology , Male , MicroRNAs/genetics , MicroRNAs/metabolism , Models, Biological , Receptor, Notch1/metabolism , Schizophrenia/pathology , Transcriptome , Young Adult
12.
Acta Biomater ; 53: 165-178, 2017 04 15.
Article in English | MEDLINE | ID: mdl-28132919

ABSTRACT

The administration of soluble growth factors (GFs) to injured tendons and ligaments (T/L) is known to promote and enhance the healing process. However, the administration of GFs is a complex, expensive and heavily-regulated process and only achieved by employing supraphysiological GF concentrations. In addition, for proper healing, specific and spatial immobilization of the GFs (s) is critical. We hypothesized that biomaterials functionalized with GF-binding peptides can be employed to capture endogenous GFs in a spatially-controlled manner, thus overcoming the need for the exogenous administration of supraphysiological doses of GFs. Here we demonstrate that the modification of films of polycaprolactone (PCL) with transforming growth factor ß1 (TGF-ß1)-binding peptides allows GFs to be captured and presented to the target cells. Moreover, using a TGF-ß reporter cell line and immunocytochemistry, we show that the GFs retained their biological activity. In human primary tendon cells, the immobilized TGF-ß1 activated TGF-ß target genes ultimately lead to a 2.5-fold increase in total collagen matrix production. In vivo implantation in rats clearly shows an accumulation of TGF-ß1 on the polymer films functionalized with the TGF-ß1-binding peptide when compared with the native films. This accumulation leads to an increase in the recruitment of inflammatory cells at day 3 and an increase in the fibrogenic response and vascularization around the implant at day 7. The results herein presented will endow current and future medical devices with novel biological properties and by doing so will accelerate T/L healing. STATEMENT OF SIGNIFICANCE: Our study describes the possibility to deliver hTGF-ß1 to human derived hamstring cells using a non-covalent bioactive strategy. The significance of our results in vivo with our functionalized biomaterial with TGF-ß1-binding peptides lies in the fact that these materials can now be employed to capture endogenous TGF-ß1 in a spatially-controlled manner, overcoming the need for exogenous administration of supra-physiological TGF-ß1 doses. Our method is different from current solutions that rely on global TGF-ß1 administration, soaking the devices with TGF-ß1, etc. Therefore we believe that our method is a significant change from current state-of-the-art in the types of devices that are used for ligament/tendon repair and that following our method can endow current and future medical devices with TGF-ß1 binding properties.


Subject(s)
Tendons/drug effects , Tendons/metabolism , Transforming Growth Factor beta1/administration & dosage , Transforming Growth Factor beta1/metabolism , Animals , Biocompatible Materials , Cells, Cultured , Collagen/biosynthesis , Drug Delivery Systems , Drug Implants , Gene Expression , Humans , Immobilized Proteins/administration & dosage , Immobilized Proteins/metabolism , Male , Materials Testing , Mink , Polyesters , Rats , Rats, Sprague-Dawley , Recombinant Proteins/administration & dosage , Recombinant Proteins/metabolism , Smad Proteins/metabolism , Tendons/cytology , Wound Healing/drug effects , Wound Healing/physiology
13.
Clin Exp Immunol ; 187(2): 251-258, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27774581

ABSTRACT

Psoriasis is a polygenic and multi-factorial disease showing ethnic differences in terms of its severity and frequency. Therapies targeting interleukin (IL)-17A, IL-17 receptor (IL-17R) and Janus kinases (JAKs) are in clinical development for the treatment of psoriasis, and their success suggests the essential role of these molecules in psoriasis. To investigate the genetic susceptibility in T helper type 17 (Th17) cell signal transduction pathways for promoting psoriasis, we performed candidate gene and linkage disequilibrium analysis. In 208 patients and 266 normal controls, we analysed 31 single nucleotide polymorphisms in 12 genes (CAMP, IL17A, IL17F, IL17RA, IL22, JAK1, JAK2, JAK3, STAT3, TLR7, TLR9 and TYK2; abbreviations: CAMP, human cathelicidin antimicrobial peptide; STAT-3, signal transducer and activator of transcription 3; TLR, Toll-like receptor; TYK2, tyrosine kinase 2). Patients with psoriasis showed a strong association for IL17F rs763780 [odds ratio (OR) = 3·27, P = 0·04], which results in a histidine-to-arginine substitution, and JAK2 rs2274471 (OR = 2·66, P = 0·02). In addition, JAK2 rs7849191 showed a protective pattern, met the significance threshold (OR = 0·77, P = 0·05) and showed a tendency for an inverse association with the frequency of early-onset psoriasis under age 40 years (P = 0·07). In haplotype analysis, JAK1 rs310241A/rs2780889T showed a protective effect (OR = 0·73, P = 0·03) in psoriasis. In conclusion, we report two new psoriasis-susceptibility loci, in IL17F and JAK2, as well as a newly identified late-onset associated protective JAK2 locus and a protective JAK1 haplotype in the Korean population.


Subject(s)
Interleukin-17/genetics , Janus Kinase 1/genetics , Janus Kinase 2/genetics , Psoriasis/genetics , Th17 Cells/physiology , Adult , Alleles , Female , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Linkage Disequilibrium , Male , Middle Aged , Polymorphism, Single Nucleotide , Republic of Korea
15.
J Plant Physiol ; 171(12): 1064-75, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-24974333

ABSTRACT

Biotic stress like pathogenic infection increases ethylene biosynthesis in plants and ethylene inhibitors are known to alleviate the severity of plant disease incidence. This study aimed to reduce the bacterial spot disease incidence in tomato plants caused by Xanthomonas campestris pv. vesicatoria (XCV) by modulating stress ethylene with 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity of Methylobacterium strains. Under greenhouse condition, Methylobacterium strains inoculated and pathogen challenged tomato plants had low ethylene emission compared to pathogen infected ones. ACC accumulation and ACC oxidase (ACO) activity with ACO related gene expression increased in XCV infected tomato plants over Methylobacterium strains inoculated plants. Among the Methylobacterium spp., CBMB12 resulted lowest ACO related gene expression (1.46 Normalized Fold Expression), whereas CBMB20 had high gene expression (3.42 Normalized Fold Expression) in pathogen challenged tomato. But a significant increase in ACO gene expression (7.09 Normalized Fold Expression) was observed in the bacterial pathogen infected plants. In contrast, Methylobacterium strains enhanced ß-1,3-glucanase and phenylalanine ammonia-lyase (PAL) enzyme activities in pathogen challenged tomato plants. The respective increase in ß-1,3-glucanase related gene expressions due to CBMB12, CBMB15, and CBMB20 strains were 66.3, 25.5 and 10.4% higher over pathogen infected plants. Similarly, PAL gene expression was high with 0.67 and 0.30 Normalized Fold Expression, in pathogen challenged tomato plants inoculated with CBMB12 and CBMB15 strains. The results suggest that ethylene is a crucial factor in bacterial spot disease incidence and that methylobacteria with ACC deaminase activity can reduce the disease severity with ultimate pathogenesis-related protein increase in tomato.


Subject(s)
Amino Acid Oxidoreductases/genetics , Genes, Plant , Methylobacterium/enzymology , Plant Proteins/genetics , Real-Time Polymerase Chain Reaction , Solanum lycopersicum/genetics , Solanum lycopersicum/microbiology , Xanthomonas campestris/physiology , Amino Acid Oxidoreductases/metabolism , Amino Acids, Cyclic/metabolism , Ethylenes/metabolism , Gene Expression Regulation, Plant , Glucan 1,3-beta-Glucosidase/metabolism , Green Fluorescent Proteins/metabolism , Solanum lycopersicum/enzymology , Solanum lycopersicum/growth & development , Phenylalanine Ammonia-Lyase/metabolism , Plant Diseases/microbiology , Plant Leaves/microbiology , Plant Proteins/metabolism , Plant Roots/growth & development , Plant Shoots/anatomy & histology
16.
Haemophilia ; 20(4): 535-40, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24471945

ABSTRACT

Many studies on epidemiology and mortality in haemophiliacs have been published in Western countries. However, few have been conducted in Asian countries. The purpose of our study was to investigate the nationwide epidemiology and mortality of haemophiliacs in Taiwan. Population-based data from the National Health Insurance Research Database between 1997 and 2009 were analysed using SAS version 9.3. The annual prevalence of haemophilia A (HA) and haemophilia B (HB) increased steadily to 7.30 and 1.34 cases per 100,000 males, respectively, in 2009. The annual crude incidence of HA and HB averaged 8.73 and 1.73 per 100,000 male births respectively. During the study period, the proportion of paediatric haemophiliacs decreased from 41.5% to 28.2% and the proportion of geriatric haemophiliacs increased from 2.5% to 5.7%. Among 493 newly diagnosed cases, the peak diagnostic ages were before 3 and between ages 10 and 40. Of the 76 cases of mortality, most patients died between the ages of 18 and 60. However, an increase in the age of mortality was noted after 2005 (P = 0.033). The overall standardized crude death rate of haemophiliacs was 10.2 per 1000 people, and the standard mortality ratio was 1.98. The annual prevalence of human immunodeficiency virus infection in haemophiliacs grossly declined from 1998 to 2009, with an average of 32.2 per 1000 haemophiliacs. This was a rare population-based study on the epidemiology and mortality of haemophilia in a Chinese population and Asian countries. The 13-year trends showed advances in haemophilia care in Taiwan.


Subject(s)
Hemophilia A/diagnosis , Hemophilia A/epidemiology , Hemophilia B/diagnosis , Hemophilia B/epidemiology , Adolescent , Adult , Age of Onset , Aged , Child , Child, Preschool , Databases, Factual , Female , Hemophilia A/mortality , Hemophilia B/mortality , Humans , Incidence , Infant , Infant, Newborn , Male , Middle Aged , Prevalence , Taiwan/epidemiology , Young Adult
17.
Heredity (Edinb) ; 112(5): 562-8, 2014 May.
Article in English | MEDLINE | ID: mdl-24398885

ABSTRACT

Changes in chromosome number and structure are important contributors to adaptation, speciation and macroevolution. In flowering plants, polyploidy and subsequent reductions in chromosome number by fusion are major sources of chromosomal evolution, but chromosome number increase by fission has been relatively unexplored. Here, we use comparative linkage mapping with gene-based markers to reconstruct chromosomal synteny within the model flowering plant genus Mimulus (monkeyflowers). Two sections of the genus with haploid numbers ≥ 14 have been inferred to be relatively recent polyploids because they are phylogenetically nested within numerous taxa with low base numbers (n=8-10). We combined multiple data sets to build integrated genetic maps of the M. guttatus species complex (section Simiolus, n=14) and the M. lewisii group (section Erythranthe; n=8), and then aligned the two integrated maps using >100 shared markers. We observed strong segmental synteny between M. lewisii and M. guttatus maps, with essentially 1-to-1 correspondence across each of 16 chromosomal blocks. Assuming that the M. lewisii (and widespread) base number of 8 is ancestral, reconstruction of 14 M. guttatus chromosomes requires at least eight fission events (likely shared by Simiolus and sister section Paradanthus (n=16)), plus two fusion events. This apparent burst of fission in the yellow monkeyflower lineages raises new questions about mechanisms and consequences of chromosomal fission in plants. Our comparative maps also provide insight into the origins of a chromosome exhibiting centromere-associated female meiotic drive and create a framework for transferring M. guttatus genome resources across the entire genus.


Subject(s)
Aneuploidy , Chromosome Mapping/methods , Chromosomes, Plant/genetics , Mimulus/genetics , Polyploidy , Centromere/genetics , Evolution, Molecular , Haploidy , Mimulus/classification , Species Specificity , Synteny
18.
Plant Dis ; 98(12): 1744, 2014 Dec.
Article in English | MEDLINE | ID: mdl-30703896

ABSTRACT

In September 2010, stem rot symptoms were observed on soybean plants (cv. Daepungkong) growing in a field located at Daegu (35.52° N, 128.35° E), South Korea. The first noticeable symptoms, observed on the top leaves, were difficult to distinguish from those of sudden death syndrome (SDS). However, after splitting the stems of symptomatic plants, typical stem rot symptoms appeared as reddish-brown to dark-brown discoloration of the pith. Stem lesions extended 15 to 20 cm upward from the soil surface. To isolate the causal agent, sections of diseased stems were surface disinfected with 1% sodium hypochlorite, placed on potato dextrose agar (PDA) containing streptomycin sulfate, and incubated at 25°C with a 12-h light regime. Two isolates were obtained (SSLNV17 and SSLNV18). Mycelia were white and floccose. Conidia (4.5 to 11.2 × 2.2 to 3.4 µm) were cylindrical to oblong-ellipsoidal, hyaline, and one-celled. Both isolates produced abundant perithecia after 3 to 4 weeks. Perithecia (205 to 331 mm in diameter) were orange to red, globose and ostiolate, with a short neck (80 to 126 mm in diameter). Unitunicate asci (88.6 to 115.3 × 14.5 to 17.3 mm) were cylindrical to clavate, with a short stalk (6.0 to 9.5 × 5.0 to 6.8 mm), and eight spores. Ascospores (13.3 to 17.5 × 10.7 to 12.7 mm) were uniseriately arranged, globose to oval, one-celled, and hyaline to pale brown, with walls with a rugose ornamentation. These morphological features are consistent with those of Neocosmospora vasinfecta var. vasinfecta (1). The internal transcribed spacer (ITS) region, partial translation elongation factor 1-alpha (EF1-α), and ß-tubulin genes of rDNA of the two isolates were sequenced using primers ITS4/ITS5 (GenBank Accession Nos. KF662732 and KF662733), EF1-728F/EF1-986R (KF758839 and KF758840), and Bt2a/Bt2b (KF771004 and KF771005), respectively. Sequences of the ITS region, EF1-α, and ß-tubulin genes of both isolates showed 99% similarity with several reported N. vasinfecta strains by BLAST analysis. Both morphological and sequence analyses confirmed that the two isolates were N. vasinfecta var. vasinfecta. Pathogenicity tests of both isolates were performed on 15 three-week-old seedlings of soybean cv. Williams inoculated with a spore suspension containing 1.0 × 106 spores/ml, using stem puncture inoculation procedure under controlled conditions (4). Control plants were inoculated in the same way with sterile water. The results were observed by splitting the stem longitudinally and checking for discoloration of the pith 4 to 5 weeks after inoculation. Reddish-brown to dark-brown discoloration was observed in the stem pith of inoculated plants, with occasional chlorosis of the leaves. Moreover, numerous orange-red perithecia were produced on the inoculated stems. However, no symptoms were visible on control plants. The pathogen was re-isolated from the diseased plants, confirming Koch's postulates. Neocosmospora stem rot of soybean was first discovered in Japan and since then it has been reported in the United States and China (2,3,4). To our knowledge, this is the first record of soybean stem rot caused by N. vasinfecta var. vasinfecta in Korea. Our report indicates that Neocosmospora stem rot is a new threat to soybean production in Korea. References: (1) P. F. Cannon and D. L. Hawksworth. Trans. Br. Mycol. Soc. 82:673, 1984. (2) Y. Gai et al. Plant Dis. 95:1031, 2011. (3) F. A. Gray et al. Plant Dis. 64:321, 1980. (4) D. V. Phillips. Phytopathology 62:612, 1972.

19.
J Appl Microbiol ; 116(2): 380-9, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24176027

ABSTRACT

AIMS: The objectives of this study were (i) to characterize white-collar (WC) orthologues of the filamentous fungus Fusarium graminearum, (ii) to investigate light-responsive phenotypes by the deletion of Fgwc-1 and Fgwc-2 genes and (iii) to examine the roles of those genes in constant light and darkness in relation to secondary metabolite synthesis and development. METHODS AND RESULTS: Production of secondary metabolites and asexual/sexual development of deletion mutants, ΔFgwc-1 and ΔFgwc-2, were assessed in constant light and darkness compared to the wild-type strain. The results showed that deletion of Fgwc-1 and Fgwc-2 impaired early onset of carotenogenesis, photoreactivation and the maturity of perithecia during sexual development. Conidiation of the ΔFgwc-1 and ΔFgwc-2 mutants was derepressed in constant light, but not in darkness. Moreover, the individual mutants produced more aurofusarin and trichothecenes than the wild-type strain in both constant light and darkness. CONCLUSIONS: Both Fgwc-1 and Fgwc-2 are required for light-dependent processes in F. graminearum, whereas light-independent processes such as aurofusarin and trichothecene biosynthesis are derepressed by deletion of these genes. Thus, Fgwc-1 and Fgwc-2 play roles as positive and negative regulators, depending on the requirement of light for biological activity. SIGNIFICANCE AND IMPACT OF THE STUDY: These results will extend the knowledge of the photobiology of Fusarium graminearum and will increase current understanding of light regulatory mechanisms mediated by white collar in secondary metabolism and fungal development.


Subject(s)
Fusarium/radiation effects , Light , Secondary Metabolism/radiation effects , Darkness , Fungal Proteins/biosynthesis , Fungal Proteins/genetics , Fusarium/genetics , Fusarium/growth & development , Fusarium/metabolism , Gene Deletion , Genes, Fungal/physiology , Phenotype , Photoreceptors, Microbial/physiology , Pigments, Biological/biosynthesis , Pigments, Biological/genetics , Real-Time Polymerase Chain Reaction , Reproduction/radiation effects , Spores, Fungal/growth & development , Spores, Fungal/radiation effects , Trichothecenes/biosynthesis , Trichothecenes/radiation effects
20.
Hong Kong Med J ; 19(5): 451-4, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24088590

ABSTRACT

Erdheim-Chester disease is a rare non-Langerhans form of systemic histiocytosis of unknown origin. We describe a 45-year-old man presenting with bilateral hydronephrosis suggestive of extrinsic urinary tract obstruction. Computed tomography revealed extensive hypodense soft tissue infiltration in the retroperitoneum surrounding the kidneys. Needle biopsy of the retroperitoneal soft tissue revealed aggregates of lipid-laden histiocytes expressing CD68 but negative for CD1a and S100 protein. The diagnosis of Erdheim-Chester disease was supported by typical radionuclide bone scinitigraphic findings. Treatment with prednisolone, sirolimus, and regular ureteric stent revision was initiated to achieve adequate urinary tract drainage. To our knowledge, this is the second patient with Erdheim-Chester disease reported in Hong Kong. A high index of suspicion is required to avoid delay in the diagnosis of this rare disease.


Subject(s)
Erdheim-Chester Disease/physiopathology , Hydronephrosis/etiology , Ureteral Obstruction/etiology , Biopsy, Needle , Erdheim-Chester Disease/diagnosis , Erdheim-Chester Disease/therapy , Hong Kong , Humans , Hydronephrosis/pathology , Male , Middle Aged , Prednisolone/therapeutic use , Retroperitoneal Space/pathology , Sirolimus/therapeutic use , Stents , Tomography, X-Ray Computed , Ureteral Obstruction/pathology , Ureteral Obstruction/therapy
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