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Isolate tracks color-coded by CC legend below figure ) .
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( C ) cap operon indels in CP5 isolates .
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Indels were identified across the cap operon and plotted against tree of all CP5 USA isolates based on mapping against S. aureus HO 5096 0412 reference .
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Isolate tracks color-coded by CC ( legend below figure ) .
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Color-coding of indels ; Vertical magenta dots indicates insertion while dark gray indicates deletion .
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For each isolate , the mapping coverage is indicated by the light grey horizontal field , with white regions demonstrating deletion of the corresponding cap genomic region .
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As such , this figure shows the partial loss of cap5D-E in a single CC97 isolate .
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( D ) cap operon indels in CP8 isolates .
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Indels were identified across the cap operon and plotted against tree of all CP8 USA isolates based on mapping against S. aureus MSSA476 reference .
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( DOCX ) Click here for additional data file.S5 Fig Specificity of immunofluorescence assay ( IFA ) for the detection of surface capsular polysaccharides in the murine bacteremia model ..
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Three different S. aureus strains : Reynolds ( CP5 ) , its isogenic CP-negative mutant , and the CP - negative Reynolds complemented with CP8-coding sequences were used to challenge mice .
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The strains were tested in a blinded fashion with two independent experiments per strain .
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S. aureus was collected at the time of challenge ( T0 ) and from the blood of infected mice 6 hr post infection ( T6 ) , and stained with rabbit anti-CP5 , or rabbit anti-CP8 antibodies , or normal rabbit IgGs .
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Bright-field ( A ) and fluorescence photographs ( B ) of IFA staining are shown for each strain at both time points .
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( TIF ) Click here for additional data file.S6 Fig Proposed Cap5D bypass mechanism ..
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( A ) Capsular polysaccharide type 5 is composed of repeat units of D-N-acetylmannosamine ( D-ManNAc ) ; L-N-acetylfucosamine ( L-FucNAc ) and D-L-acetylfucosamine ( D-FucNAc ) .
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Cap5D is associated with synthesis of the D-FucNAc precursor ( Li et al. Internatl .
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J. Med .
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Micro .
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2014 ) and Cap5E is primarily associated with synthesizing L-FucNAc precursor ( Miyafusa et al. FEBS Lett .
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2013 ) .
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( B ) Cap5D is a 4 , 6-dehydratase that converts UDP-D-GlcNAc to a D-FucNAc precursor , while Cap5E has 4 , 6-dehydratase and 5-epimerase activity that converts UDP-D-GlcNAc to an L-FucNAc precursor but can also generate the analogous D-FucNAc precursor in a reverse epimerization reaction ( Miyafusa et al. FEBS Lett .
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2013 ) .
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We propose that for S. aureus USA300 strains where the cap5D gene has a premature stop codon , the UDP-D-FucNAc precursor UDP-2-acetoamino-2 , 6-dideoxy-a-D-xylo-4-hexulose ( highlighted in orange ) is derived as byproduct of the CapE epimerase reaction .
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( DOCX ) Click here for additional data file .
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Improvement in the quality of life of patients with rhododendrol-induced leukoderma after camouflaging with dihydroxyacetone cream .
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Rhododendrol , 4 ‐ ( 4 ‐ hydroxyphenyl ) ‐ 2 ‐ butanol , Rhododenol ( Kanebo Cosmetics Inc ., Tokyo , Japan ) ( RD ) is a whitening agent , which was approved as a quasi ‐ drug by the Ministry of Health , Labor and Welfare of Japan in 2008 .
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1 However , cosmetic products containing RD were withdrawn from the market in 2013 because some users had developed leukoderma at the sites of product application .
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1 While in more than 80 % of patients RD ‐ induced leukoderma ( RDIL ) was ameliorated , it was worsened or showed no change in approximately 16 % .
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1 Camouflage therapies are also often employed in cases of vitiligo to reduce the emotional stress of the patients by making the depigmented lesions inconspicuous .
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2 A self ‐ tanning agent containing dihydroxyacetone ( DHA ) is easy to apply and retains color stably for a while .
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3 As frequent applications are not needed , it is preferred in camouflaging the neck and hands , from which it may be rubbed off easily .
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4 A study has reported the usefulness of the self ‐ tanning lotion containing DHA in cases of RDIL with refractory lesions on the neck and hands .
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5 However , the challenges of color matching in the intricately formed depigmentation area and skin dryness after application persist .
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To solve these problems , we examined the usefulness of cream ‐ based formulations that are easy to apply and able to retain moisture in patients with RDIL.Eight patients with refractory RDIL on the backs of the hands and / or necks , who had been treated at the Department of Dermatology , Fujita Health University Hospital , were enrolled in this prospective observational study approved by the institutional review board of Fujita Health University .
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All of the participants were Japanese women with an average age of 54 years ( range , 44 – 81 ) .
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We explained the study in detail to the patients , who provided written informed consent before participating.Two types of creams , containing glycerol , diglycerol or 1,3 ‐ butanediol as moisturizing ingredients and DHA at a concentration of 1 % or 3 % were used .
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The patients were asked to apply these creams at the site of the lesion , a maximum of twice daily for 2 months between July and September .
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The type of cream and frequency of application was decided by the patients themselves based on the condition of colored skin.After the application of DHA creams for 1 month , the lesions of all patients were inconspicuous , and the camouflage lasted for up to 2 months during application .
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The lesions disappeared along with desquamation of the stratum corneum within 3 weeks after discontinuation of application .
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Typical examples are shown in Figure 1 .
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No skin complications , such as eczema , dryness and erythema , were seen during application and up to 3 weeks after discontinuation in the assessment by an expert dermatologist .
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We examined the change in quality of life ( QOL ) as measured by using the Japanese version of Skindex ‐ 16 , 6 which is a well ‐ accepted instrument to evaluate dermatology ‐ specific QOL .
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7 The total Skindex ‐ 16 scores were significantly lower at 2 months than those before the commencement of application of the creams ( Fig. S1a ) , showing considerable improvement in QOL.Interestingly , this improvement lasted up to 3 weeks after discontinuation of the cream , suggesting that the patients were secure regarding the camouflage provided by the cream .
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The responses were categorized as subscales of symptoms , emotions and functions .
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Compared to baseline , especially , the emotions subscale score decreased significantly during application and also after discontinuation ( Fig. S1b ) .
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The functioning subscale scores decreased significantly , while the symptoms subscale scores were unchanged during the entire duration of the study ( Fig. S1c , d ) .
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Additionally , there were few negative answers in the self ‐ assessment questionnaires administered at the end of the study regarding the comfort of use , functionality of creams and usefulness ( Fig. S2 ) .
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Almost all patients agreed or agreed somewhat to the questions regarding the benefit of the cream and their desire to continue using.A previous study demonstrated the usefulness of a self ‐ tanning lotion for the treatment of refractory RDIL ; however , only half or less than half of the patients wanted to continue using it .
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5 In contrast , in this study , almost all patients showed their willingness to continue using the creams.Meanwhile , a patient who had a complicated form of depigmentation with patchy repigmentation expressed difficulty in applying the cream to the depigmented area .
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Thus , we must consider the condition of depigmentation while prescribing the self ‐ tanning agent.In summary , we demonstrated that DHA ‐ containing moisturizing creams could significantly improve the QOL of patients with RDIL .
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Further studies are warranted to clarify the individual ‐ and site ‐ based differences in responding to DHA .
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CONFLICT OF INTEREST .
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This study was approved by the Conflict of Interest Committee of Fujita Health University ( CI18 ‐ 288 ) and was conducted as a contract study of Kao Corporation .
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All of the co ‐ authors are employees of Kao Corporation .
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Supporting information .
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Figure S1 .
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Improvement in quality of life ( QOL ) as evaluated by Skindex ‐ 16 .
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Changes in ( a ) Skindex ‐ 16 , ( b ) total scores , ( c ) emotions subscale scores , ( d ) functioning subscale scores and ( d ) symptoms subscale scores .
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Values are expressed as mean Β± standard deviation ( n = 8) .
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The Wilcoxon signed ‐ rank test was used for statistical analysis for comparison with the baseline .
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* P < 0.05 , * * P < 0.01.Click here for additional data file .
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Figure S2 .
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Analysis of the self ‐ assessment questionnaires for usefulness , ease of use and functionality .
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Percentage of responses ( n = 8) .
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Click here for additional data file .
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