“
“Purpose: Multifactorial etiological factors contribute to denture stomatitis (DS), a type of oral candidiasis; however, unlike other oral candidiasis, DS can occur in a healthy person wearing a denture. In this study, we therefore attempt to explore the association between candida, denture, and mucosal tissue using (1) exfoliative cytology, (2) the candidal levels present in saliva, on mucosal tissues and on denture surfaces, and (3) the salivary flow rate and xerostomic symptoms. Materials and Methods: A cross-sectional study enrolled 32 edentulous participants,

17 without DS as controls and 15 with DS (Newton’s classification type II and III). Participants with systemic or other known oral conditions were excluded. Participants completed a xerostomia questionnaire, and salivary flow rates were measured. Samples

of unstimulated whole saliva Volasertib (UWS) and stimulated whole saliva (SWS) were collected. UWS was used for fungal culturing. Periodic acid-Schiff (PAS) stain and quantitative exfoliative cytology were performed on samples from affected and unaffected mucosa from each participant. Levels of Candida species (albicans and non-albicans) were determined in salivary samples (expressed as colony-forming units, CFU), as well as from swab samples obtained from denture fitting surfaces, in addition to affected and unaffected mucosa. Results: There were no significant differences in salivary flow rates, mucosal wetness, or frequency of reported dry mouth comparing participants with and without DS. Exfoliative cytology of mucosal smears demonstrated significantly ABT-737 cost higher (p= 0.02) inflammatory cell counts in DS patients, as compared with smears of healthy denture-wearers.

Candida albicans was significantly more prevalent in saliva (p= 0.03) and on denture surfaces (p= 0.002) of DS participants, whereas mucosal candidal counts and the presence of cytological hyphae did not show significant difference comparing DS to healthy this website participants. Conclusions: In this investigation, we presented a unique group of healthy edentulous patients. This population may reflect the general DS population without systemic or other oral diseases. The prominent etiological factor for DS in this population is the presence of candida in denture and saliva. We found that other factors such as saliva flow/xerostomia, fitting of the denture, and the presence of candida in the mucosa, are less important in this population. Therefore, DS treatments in healthy patients should first focus on sanitization of an existing denture and/or fabrication of a new denture. “
“Prosthodontic patients are often at a high risk for caries, and assessing that risk prior to treatment is important. Historically, the nature of dental education and clinical practice has oriented clinicians toward recognizing and correcting the damaging effects of caries, rather than actively assessing and managing caries risk potential.

“
“Purpose: Multifactorial etiological factors contribute to denture stomatitis (DS), a type of oral candidiasis; however, unlike other oral candidiasis, DS can occur in a healthy person wearing a denture. In this study, we therefore attempt to explore the association between candida, denture, and mucosal tissue using (1) exfoliative cytology, (2) the candidal levels present in saliva, on mucosal tissues and on denture surfaces, and (3) the salivary flow rate and xerostomic symptoms. Materials and Methods: A cross-sectional study enrolled 32 edentulous participants,

17 without DS as controls and 15 with DS (Newton’s classification type II and III). Participants with systemic or other known oral conditions were excluded. Participants completed a xerostomia questionnaire, and salivary flow rates were measured. Samples

of unstimulated whole saliva NVP-BKM120 in vivo (UWS) and stimulated whole saliva (SWS) were collected. UWS was used for fungal culturing. Periodic acid-Schiff (PAS) stain and quantitative exfoliative cytology were performed on samples from affected and unaffected mucosa from each participant. Levels of Candida species (albicans and non-albicans) were determined in salivary samples (expressed as colony-forming units, CFU), as well as from swab samples obtained from denture fitting surfaces, in addition to affected and unaffected mucosa. Results: There were no significant differences in salivary flow rates, mucosal wetness, or frequency of reported dry mouth comparing participants with and without DS. Exfoliative cytology of mucosal smears demonstrated significantly MLN8237 nmr higher (p= 0.02) inflammatory cell counts in DS patients, as compared with smears of healthy denture-wearers.

Candida albicans was significantly more prevalent in saliva (p= 0.03) and on denture surfaces (p= 0.002) of DS participants, whereas mucosal candidal counts and the presence of cytological hyphae did not show significant difference comparing DS to healthy check details participants. Conclusions: In this investigation, we presented a unique group of healthy edentulous patients. This population may reflect the general DS population without systemic or other oral diseases. The prominent etiological factor for DS in this population is the presence of candida in denture and saliva. We found that other factors such as saliva flow/xerostomia, fitting of the denture, and the presence of candida in the mucosa, are less important in this population. Therefore, DS treatments in healthy patients should first focus on sanitization of an existing denture and/or fabrication of a new denture. “
“Prosthodontic patients are often at a high risk for caries, and assessing that risk prior to treatment is important. Historically, the nature of dental education and clinical practice has oriented clinicians toward recognizing and correcting the damaging effects of caries, rather than actively assessing and managing caries risk potential.

3A) and miR-206, an miRNA with the identical miR-1 seed-sequence but a different sequence at its 3′ end, were used for comparison with miR-1. Transfection of HepG2.2.15 cells with m-miR-1 and miR-206 did not enhance HBV replication (Fig. 3A). Further, cotransfection of miR-1 and its specific antisense inhibitor anti-miR-1 abolished the increase of HBV RI in HepG2.2.15, whereas the enhancing effect of miR-1 on HBV RI remained unchanged if an

unrelated anti-miR-C was cotransfected (Fig. 3B, lane 3). Consistently, knockdown of argonaute-2 (Ago2), a main component of RNA-induced silencing complex, by specific siRNA appeared to attenuate the effect of miR-1 (Fig. 3C, lane 4). These results suggested that up-regulation of HBV replication was mediated by miR-1-guided RISC formation. A critical feature of a direct interaction between miRNAs and target mRNAs is the presence of the corresponding seed sequences in the target.2 However, check details the complementary sequence (ACATTCC) of miR-1 seed sequence which was required for its binding to target mRNA was not found in the HBV genomic sequence. Consistently, cotransfection of pMIR-REPORT system Adriamycin with cloned full length or four fragments of HBV genome and miR-1 into HepG2 cells did not result in a decrease of luciferase gene expression

(Supporting Information Fig. 3). Taken together, the data suggest that it is unlikely that miR-1 regulates HBV gene expression and replication by a direct interaction with genomic sequence of HBV. These results suggested that selleck kinase inhibitor miR-1 may act on specific cellular targets and thereby enhances HBV replication and gene expression in an indirect manner. Previously, a member of class II histone deacetylase (HDAC4) was identified as a cellular target of miR-1.22 Similarly, transfection with miR-1

led to a markedly reduced expression level of HDAC4 protein in HepG2.2.15 cells (Fig. 4A). The reduction of HDAC4 by miR-1 hinted at the potential role HDAC4 on HBV replication, similar to the recent results of HDAC1.23 Indeed, the knockdown of HDAC4 expression by specific siRNAs led to nearly a 2.5-fold increase in HBV replication in HepG2.2.15 cells (Fig. 4B), as well as the use of broad-spectrum HDAC inhibitor TSA (Supporting Information Fig. 4). Furthermore, cotransfection of an HDAC4 expression vector pHDAC4 with miR-1 could attenuate the increased replication of HBV (Fig. 4C). We concluded that HDAC4 is a target of miR-1 and may play a significant role in the action of miR-1 on HBV replication. The modulation of HDAC4 expression by miR-1 may lead to changes of HBV promoter activity. Thus, four pGL3-based luciferase reporter constructs pSP1, pSP2, pCP, and pXP containing the region of HBV SP1, SP2, core, and X promoters were cotransfected with miR-1 into HepG2.2.15 cells. The ectopic expression of miR-1 increased the level of transcription activity of the HBV core promoter about 3.0-fold but had no effect on the other three promoters (Fig. 5A).

20 indicates moderate to fair agreement, 0.20 〈κ〉 0 indicates slight agreement, and κ = 0 indicates no agreement. Logistic regression and receiver operating characteristic (ROC) analysis were applied selleck chemicals to each diagnostic modality individually and in combination to predict hepatic fibrosis and PHT; the positive predictive value (PPV) and the negative predictive value (NPV) were included. An area under the receiver operating characteristic curve (AUROC) >0.80 indicated potential diagnostic utility.

Multivariate logistic regression, corrected for age, FEV at enrollment, treatment with Urso, the presence of steatosis, and the presence of diabetes mellitus, was performed to identify factors associated with PHT, the occurrence of which was evaluated with Kaplan-Meier statistics. A backward elimination approach was used to remove nonsignificant variables and to determine the most parsimonious model. A Cox proportional hazards model was used to determine factors independently associated Raf inhibitor with the time to the development of PHT. All statistical significance was taken at the 95% confidence interval. The 40 children (24 females and 16 males) were 2.38 to 18.73 years old at enrollment (median age = 10.64 years). Most (96%) were Caucasian, 68% were Δf508 homozygotes, 20% had CFRD, 43% underwent gastrostomy for supplemental nutrition,

and 35% had meconium ileus at birth. The median FEV1 value was 83.5%. At enrollment, 9 of 40 had evidence of PHT, as defined previously (Table 1). No patient was found to have or was suspected of having portal learn more vein thrombosis. During follow-up (up to 12 years; median = 9.5 years), seven (17.5%) died: five (12.5%) from respiratory failure (three also had end-stage liver disease), one (2.5%) from end-stage liver disease alone (on a transplant waiting list), and one from leukemia (2.5%). Three (7.5%) received a transplant (liver transplant, lung transplant, or heart and lung transplant). Another eight patients developed PHT, as defined previously, during follow-up (median age = 12.9 years). Seventeen of the 40 patients (including the 9 patients with PHT defined at enrollment)

had PHT, which was present in the majority of those who died (6 of 7) or underwent transplantation (2 of 3). Seventy-seven of the 80 biopsy specimens had at least 5 portal tracts allowing adequate assessment (range = 5-13). The 3 specimens deemed inadequate were from different patients, and the alternate core had F2 or F3; this allowed fibrosis staging to be reported in all 40 patients (Table 2): F0 (no fibrosis) in 9 (22.5%), F1 (mild fibrosis) in 10 (25%), F2 (moderate fibrosis) in 10 (25%), F3 (advanced fibrosis) in 9 (22.5%), and F4 (cirrhosis) in 2 (5%). Steatosis was evident in 28 of 40 (70%). Dual-pass biopsy improved the detection of fibrosis (F1-F4): the first pass detected fibrosis in 26 patients, and the second detected fibrosis in another 5 patients (12.5%, P = 0.002).

3 Much attention has therefore been focused on whether noninvasive methods can detect clinically significant steatosis, fibrosis, or cirrhosis or can discriminate between simple steatosis and NASH in NAFLD patients.4-6 Several imaging techniques may be used to detect steatosis but are not sufficient to stage liver fibrosis. In addition, several markers including extracellular matrix components or enzymes involved in their degradation or synthesis have been described to predict the degree of fibrosis.7, 8 However, the utility of these markers as predictors of liver damage is limited and controversial. Clinical decision making often requires differentiation of minimal from intermediate stages

of fibrosis. The inability of serological fibrosis markers to correctly identify patients with intermediate fibrosis stages has been suggested to be 30%-70%.9 Small molecule library solubility dmso For instance, a combination of different parameters involved in fibrogenesis was shown learn more to accurately detect fibrosis, but the discriminative power between early fibrosis stages was limited.10, 11 Thus, there is an urgent need to develop simple, noninvasive tests that can identify the stage of liver disease and

accurately distinguish NASH from simple steatosis. Increasing evidence suggests an important role for hepatocyte apoptosis in the progression of NALFD and other liver diseases.12, 13 During apoptosis, caspases are activated and cleave various substrates, including cytokeratin-18 (CK-18), a major intermediate filament protein in hepatocytes.14, 15 Apoptosis of hepatocytes is further associated with the release of caspase-cleaved CK18 fragments in the bloodstream. CK-18 cleavage generates

a neoepitope that can be detected by the monoclonal antibody M30 and therefore allows the assessment of apoptosis specifically of epithelial cells by an enzyme-linked immunosorbent assay (ELISA). In contrast, another assay, the M65 ELISA, detects both caspase-cleaved and uncleaved CK-18 and is therefore used as a marker of overall death including apoptosis and necrosis. Using the M30 antibody, we initially demonstrated that CK-18 cleavage and apoptosis are increased in liver tissue of patients with various liver diseases.16, 17 Moreover, we could detect a caspase-generated CK-18 fragment in sera of patients with liver disease but selleck products not in healthy individuals.18 Subsequently, we and others demonstrated that caspase-generated CK-18 fragments are increased in sera of patients with various acute or chronic liver diseases.19-23 Furthermore, it was recently shown that the plasma concentration of the CK-18 fragments accurately differentiated NASH from NAFL.24-26 These results therefore suggest a potential use of CK18 fragments as a biomarker for the staging of chronic liver disease. Whether apoptosis is the sole cell death mechanism involved in liver diseases is currently unknown.

These patients had 3 years of stored sera preceding recruitment (taken with informed consent) and were HBsAg-positive and HBeAg-negative during these 3 years. Serum Dinaciclib HBV DNA and HBsAg levels were measured at five time points: 3 years, 2 years, 1 year, and 6 months before recruitment

and at date of recruitment (i.e., baseline). These control patients were matched with patients with HBsAg seroclearance at a ratio of 1:1 for age and sex at all time points. The number of stored serum available for these tests were 203, 189, 187, 190, and 197 at the time points of 3 years, 2 years, 1 year, 6 months, and baseline, respectively. None of the patients from the two groups received any antiviral therapy during the entire follow-up period. This study was approved by the Institutional Review Board, the University of Hong Kong and West Cluster of Hospital Authority, Hong this website Kong. Serologic markers, including serum HBsAg, HBeAg, anti-HBs, and antibody to hepatitis B e antigen (anti-HBe), were measured by Abbott Laboratories (Chicago, IL). Serum HBV DNA levels were measured using the Cobas Taqman assay (Roche Diagnostics, Branchburg,

NJ), with a lower limit of detection of 20 IU/mL. Serum HBsAg levels were measured using the Elecsys HBsAg II assay (Roche Diagnostics, Gmbh, Mannheim, Germany),21 with a linear range of 0.05-52,000 IU/mL. Samples with HBsAg levels higher than 52,000 IU/mL were retested at a dilution of 1:100, according to the manufacturer’s instructions. One hundred randomly chosen patients with HBsAg seroclearance, followed by 100 age- and sex-matched controls, were chosen for the determination of HBV genotype using the INNO-LIPA HBV genotyping assay, which was performed according to the manufacturer’s instructions (Innogenetics, Gent, Belgium). All continuous values were expressed in median check details (range). For patients with undetectable serum HBV DNA or HBsAg, the results were taken as the lower limit of detection (20 and 0.05 IU/mL, respectively). The HBsAg (log IU/mL)/HBV DNA (log IU/mL) ratio, which reflects the percentage of subviral particles over virions,

was measured. To compare the characteristics between the two patient groups, Mann-Whitney’s U test or Kruskal-Wallis’ test, when appropriate, was used for continuous variables with a skewed distribution; the chi-squared test was used for categorical variables. Correlation between serum HBsAg levels and other variables, because of the repeated observations noted per patient, was performed using Pearson’s weighted correlation coefficient.22 The predictions of HBsAg seroclearance were first examined by the construction of corresponding receiver operating characteristic (ROC) curves, followed by the assessment of overall accuracy by areas under the curves (AUCs). Then, the optimal level of prediction was attained by Youden’s index,23, 24 which is defined as the sensitivity plus the specificity minus 1.

This has been interpreted to be maintaining a baseline factor level >1%. Given impending product advances and taking note that normal FVIII/FIX activity is 50%–150%, it may be time to consider whether a 1% target is sufficient to prevent bleeding or if it is simply conveniently based on existing economics and treatment protocol burdens (frequency of dosing and venous access). Although it may seem impossible to imagine, based on currently available therapies, the paradigm may shift to a point were treatment goals could more closely mimic a check details normal state. Recognition of the significance and benefit of preventing sub-clinical

bleeds (microhemorrhages) may be an important factor in optimizing long-term outcomes [40]. Until recently, there has been little evidence to suggest a baseline FVIII/FIX level >1% might be preferred for some patients. A recent analysis of low frequency bleeding data demonstrated the association between joint bleeds and baseline FVIII find more activity levels. Clinical data on bleeding according to baseline FVIII levels suggest that absence of joint bleeding may only be reached when approaching FVII levels of 15% [41,42]. Patients with low baseline factor

levels (<5%) had the highest risk for joint bleeds, and patients with clotting factor activity levels of 10% and higher had a very low risk, which approximated no expected joint bleeds in patients with baseline factor activity of 15% and higher. The analysis also demonstrated an 18% reduction in joint bleed frequency with every percent increase learn more in residual clotting factor activity in moderate and mild patients treated on demand [42]. With FVIII/FIX activity levels of 1% significant care is still required in daily living thus limiting the ability for full social integration equivalent to someone without a bleeding disorder. It is wholly insufficient to accommodate major or accidental trauma causing bleeding. The fear of traumatic injury remains a constant. Although advances over the past 50 years have brought us closer to the opportunity of having a near normal life expectancy, over time, future generations of patients should aspire to achieve full integration opportunities

in all aspects of life. Improving patient quality of life should drive treatment decisions, not economics. Although theoretically a trough level of 15% may be ideal to achieve the absence of joint bleeding, it is, in the near term, unattainable given economic constraints on demand. However, we should aspire to an absence of joint bleeds. Moving forward incrementally from 1% to higher baseline factor levels (e.g. 3% or 5%) would be a step in the right direction. Prophylaxis, even as currently practiced in countries where there are no significant resource constraints, is an expensive treatment and is only possible if significant resources are allocated to haemophilia care. The high cost is a barrier to widespread acceptance of prophylaxis globally [40].

This has been interpreted to be maintaining a baseline factor level >1%. Given impending product advances and taking note that normal FVIII/FIX activity is 50%–150%, it may be time to consider whether a 1% target is sufficient to prevent bleeding or if it is simply conveniently based on existing economics and treatment protocol burdens (frequency of dosing and venous access). Although it may seem impossible to imagine, based on currently available therapies, the paradigm may shift to a point were treatment goals could more closely mimic a HKI-272 in vitro normal state. Recognition of the significance and benefit of preventing sub-clinical

bleeds (microhemorrhages) may be an important factor in optimizing long-term outcomes [40]. Until recently, there has been little evidence to suggest a baseline FVIII/FIX level >1% might be preferred for some patients. A recent analysis of low frequency bleeding data demonstrated the association between joint bleeds and baseline FVIII Protein Tyrosine Kinase inhibitor activity levels. Clinical data on bleeding according to baseline FVIII levels suggest that absence of joint bleeding may only be reached when approaching FVII levels of 15% [41,42]. Patients with low baseline factor

levels (<5%) had the highest risk for joint bleeds, and patients with clotting factor activity levels of 10% and higher had a very low risk, which approximated no expected joint bleeds in patients with baseline factor activity of 15% and higher. The analysis also demonstrated an 18% reduction in joint bleed frequency with every percent increase selleck in residual clotting factor activity in moderate and mild patients treated on demand [42]. With FVIII/FIX activity levels of 1% significant care is still required in daily living thus limiting the ability for full social integration equivalent to someone without a bleeding disorder. It is wholly insufficient to accommodate major or accidental trauma causing bleeding. The fear of traumatic injury remains a constant. Although advances over the past 50 years have brought us closer to the opportunity of having a near normal life expectancy, over time, future generations of patients should aspire to achieve full integration opportunities

in all aspects of life. Improving patient quality of life should drive treatment decisions, not economics. Although theoretically a trough level of 15% may be ideal to achieve the absence of joint bleeding, it is, in the near term, unattainable given economic constraints on demand. However, we should aspire to an absence of joint bleeds. Moving forward incrementally from 1% to higher baseline factor levels (e.g. 3% or 5%) would be a step in the right direction. Prophylaxis, even as currently practiced in countries where there are no significant resource constraints, is an expensive treatment and is only possible if significant resources are allocated to haemophilia care. The high cost is a barrier to widespread acceptance of prophylaxis globally [40].

Professor Mamoru Watanabe has made strenuous

efforts to improve the peer review system. He introduced an on-line submission system to JG soon after he became Editor-in-Chief. He pushed associate editors to make a quick decision process, and subsequently the average time from submission to first decision in 2011 became 14 days. In his Editor-In-Chief term of JG, Dr Watanabe established strict initial evaluation processes by the editor, and leading by example, he himself made such an initial decision for 15–20 papers each week. More than 70% of the submitted papers were subjected to immediate rejection on the basis of unsuitability for publication. This category included most retrospective KU57788 clinical studies that failed to establish new concepts, and some prospective clinical studies with only small numbers of subjects. With these efforts, the acceptance rate of JG decreased from 26% in 2004 to 16% in 2011. Watanabe also promoted JG to many leaders of gastroenterology and hepatology in other countries, especially at the time of international meetings. This resulted in a substantial increase in the number of submissions, from 361 in 2004 to 985 in 2011. In particular, the submission rate from abroad increased from click here 25% in 2004 to 63% in 2011. With

his great efforts, we are sure that the impact factor of JGH will increase and reach 5.0 in 2–3 years. Dr Watanabe is now a Councilor of the JSGE, responsible for establishing and revising clinical guidelines for all areas of gastroenterology and hepatology. He will be the Secretary-General of the 100th commemorative meeting for

the JSGE in 2014. Mamoru Watanabe is one of the top leaders in the IBD area and has been serving as a chairman of The Research Committee of Inflammatory selleck screening library Bowel Disease, Research on Measures of Intractable Disease organized by the Japanese Ministry of Health, Labor and Welfare. He is also a committee member of the Science Council of Japan and councilors for many major medical societies, such as the Japanese Society of Internal Medicine, the Japan Gastroenterological Endoscopy Society, and the Japanese Society for Mucosal Immunology. Dr Watanabe’s activities are not limited to Japan. He has delivered numerous invited and honorary lectures on clinical and basic research at international meetings. He has been a councilor of the Immunology/Microbiology/IBD section of the AGA for years, and regularly chairs IBD sessions each year at Digestive Diseases Week (DDW) in the USA. In DDW 2012 San Diego, he had a chance to give a Meet-the-Investigator Luncheon for his excellent basic works. For his research area, he has been serving as the Councilor of the Society of Mucosal Immunology as a representative of the Asia-Pacific region for 4 years.

Professor Mamoru Watanabe has made strenuous

efforts to improve the peer review system. He introduced an on-line submission system to JG soon after he became Editor-in-Chief. He pushed associate editors to make a quick decision process, and subsequently the average time from submission to first decision in 2011 became 14 days. In his Editor-In-Chief term of JG, Dr Watanabe established strict initial evaluation processes by the editor, and leading by example, he himself made such an initial decision for 15–20 papers each week. More than 70% of the submitted papers were subjected to immediate rejection on the basis of unsuitability for publication. This category included most retrospective find more clinical studies that failed to establish new concepts, and some prospective clinical studies with only small numbers of subjects. With these efforts, the acceptance rate of JG decreased from 26% in 2004 to 16% in 2011. Watanabe also promoted JG to many leaders of gastroenterology and hepatology in other countries, especially at the time of international meetings. This resulted in a substantial increase in the number of submissions, from 361 in 2004 to 985 in 2011. In particular, the submission rate from abroad increased from selleck products 25% in 2004 to 63% in 2011. With

his great efforts, we are sure that the impact factor of JGH will increase and reach 5.0 in 2–3 years. Dr Watanabe is now a Councilor of the JSGE, responsible for establishing and revising clinical guidelines for all areas of gastroenterology and hepatology. He will be the Secretary-General of the 100th commemorative meeting for

the JSGE in 2014. Mamoru Watanabe is one of the top leaders in the IBD area and has been serving as a chairman of The Research Committee of Inflammatory selleck chemical Bowel Disease, Research on Measures of Intractable Disease organized by the Japanese Ministry of Health, Labor and Welfare. He is also a committee member of the Science Council of Japan and councilors for many major medical societies, such as the Japanese Society of Internal Medicine, the Japan Gastroenterological Endoscopy Society, and the Japanese Society for Mucosal Immunology. Dr Watanabe’s activities are not limited to Japan. He has delivered numerous invited and honorary lectures on clinical and basic research at international meetings. He has been a councilor of the Immunology/Microbiology/IBD section of the AGA for years, and regularly chairs IBD sessions each year at Digestive Diseases Week (DDW) in the USA. In DDW 2012 San Diego, he had a chance to give a Meet-the-Investigator Luncheon for his excellent basic works. For his research area, he has been serving as the Councilor of the Society of Mucosal Immunology as a representative of the Asia-Pacific region for 4 years.