The effect of nocturnal wear of dentures on the sleep quality: a systematic review and meta-analysis.

PURPOSE: The effect of nocturnal wear of denture on sleep quality and integrity is still not well understood. Therefore, this systematic review was conducted to provide evidence on this topic. METHODS: Electronic searches were conducted from 1964 up to September 2015, using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Only publications in English or French, in which sleep quality of edentate adult individuals wearing dentures at night was compared to those not wearing were included in the review. Random effects models were used to pool the effect sizes. RESULTS: A total of 10 studies were included in the systematic review and 5 in the meta-analysis. No statistically significant difference between sleeping with denture and without denture was found for the Apnea-Hypopnea Index (AHI; Standard Mean Difference = -0.60, 95 % CI -1.67-0.47; Z = -1.10; p = 0.27). However, there was considerable heterogeneity in the studies included in the meta-analysis (Tau2 = 1.34; Q-value = 59.32, df = 4 (P < 0.0001); I2 = 93.3 %). When results from randomized controlled trials (RCTs) were pooled in subgroup analyses of AHI, there was a tendency towards favoring sleeping without dentures (P = 0.059) and no evidence of heterogeneity between studies (Tau2 = 0.000; Q-value = 0.06, df = 1 (P = 0.80); I2 = 0.000 %). CONCLUSION: The current evidence suggests that there is no difference in the sleep quality and integrity of individuals wearing or not wearing their denture during sleep. However, the results of randomized controlled trials favoring sleeping without dentures and the likely presence of bias in the previous studies indicate the need for further randomized controlled trials for the development of clinical guideline.

Cobalt-Chromium Metallosis With Normal Electroretinogram.

BACKGROUND: Ocular cobalt toxicity is a rare phenomenon reported with increased frequency due to the rise of cobalt-chromium metal hip implants. We report the case of a 66-year-old previously healthy man who developed decreased vision due to cobalt-chromium toxicity from a metal-on-metal hip arthroplasty. Our objective was to determine whether the origin of his visual loss was due to toxicity of the optic nerve, of the retina, or of both. METHODS: Ocular examination, 10-2 SITA-Standard Humphrey Visual Field (VF), standard full-field electroretinogram (ERG) as indicated by the International Society for Clinical Electrophysiology of Vision (ISCEV), multifocal electroretinogram (mfERG), multifocal visual evoked potentials (mfVEP), and optical coherence tomography (OCT) were conducted. RESULTS: Ocular examination revealed decreased visual acuity, poor color vision, normal funduscopy, and cecocentral scotomas on VF testing. Because his right eye was amblyopic since childhood, test results from only the left eye are shown. Electrophysiology studies revealed an ISCEV standard full-field ERG with photopic and scotopic responses within normal limits, mfERG with amplitudes and latencies within normal limits, and mfVEP with latencies within normal limits, but with decreased central amplitudes. Peripapillary and macular OCT showed retinal nerve fiber layer and retinal ganglion cell-inner plexiform layer thickness within normal limits. CONCLUSION: Because decreased color vision and cecocentral scotoma on 10-2 VF are most consistent with toxic optic neuropathy, and decreased central amplitudes on mfVEP are suggestive of neural dysfunction, we hypothesize that our patient presented with an early stage of optic nerve toxicity that was not yet apparent as a structural abnormality on OCT.

Predictors of Free Sugars Intake Trajectories across Early Childhood-Results from the SMILE Birth Cohort Study.

Foods and beverages high in free sugars can displace healthier choices and increase the risk of weight gain, dental caries, and noncommunicable diseases. Little is known about the intake of free sugars across early childhood. This study aimed to examine the longitudinal intake from 1 to 5 years of free sugars and identify the independent maternal and child-related predictors of intake in a cohort of Australian children participating in the Study of Mothers' and Infants' Life Events Affecting Oral Health (SMILE). Free sugars intake (FSI) was previously estimated at 1, 2, and 5 years of age, and three distinct FSI trajectories were determined using group-based trajectory modelling analysis. This study utilized multinomial logistic regression to identify the maternal and child-related predictors of the trajectories. The risk of following the 'high and increasing' trajectory of FSI compared to the 'low and fast increasing' trajectory was inversely associated with socio-economic disadvantage (aRRR 0.83; 95% CI 0.75-0.92; p < 0.001), lower for females (aRRR 0.56; 95% CI 0.32-0.98; p = 0.042), and higher in children with two or more older siblings at birth (aRRR 2.32; 95% CI 0.99-5.42; p = 0.052). Differences in trajectories of FSI were evident from an early age and a high trajectory of FSI was associated primarily with socio-economic disadvantage, providing another example of diet quality following a social gradient.

Omics analysis unveils changes in the metabolome and lipidome of Caenorhabditis elegans upon polydopamine exposure.

Polydopamine (PDA) is an insoluble biopolymer with a dark brown-black color that forms through the autoxidation of dopamine. Because of its outstanding biocompatibility and durability, PDA holds enormous promise for various applications, both in the biomedical and non-medical domains. To ensure human safety, protect health, and minimize environmental impacts, the assessment of PDA toxicity is important. In this study, metabolomics and lipidomics assessed the impact of acute PDA exposure on Caenorhabditis elegans (C. elegans). The findings revealed a pronounced perturbation in the metabolome and lipidome of C. elegans at the L4 stage following 24 hours of exposure to 100 µg/mL PDA. The changes in lipid composition varied based on lipid classes. Increased lipid classes included lysophosphatidylethanolamine, triacylglycerides, and fatty acids, while decreased species involved in several sub-classes of glycerophospholipids and sphingolipids. Besides, we detected 37 significantly affected metabolites in the positive and 8 in the negative ion modes due to exposure to PDA in C. elegans. The metabolites most impacted by PDA exposure were associated with purine metabolism, biosynthesis of valine, leucine, and isoleucine; aminoacyl-tRNA biosynthesis; and cysteine and methionine metabolism, along with pantothenate and CoA biosynthesis; the citrate cycle (TCA cycle); and beta-alanine metabolism. In conclusion, PDA exposure may intricately influence the metabolome and lipidome of C. elegans. The combined application of metabolomics and lipidomics offers additional insights into the metabolic perturbations involved in PDA-induced biological effects and presents potential biomarkers for the assessment of PDA safety.

Development of an extemporaneous preparation formulation using a simple and non-solubilizing matrix for first in human clinical study.

Extemporaneous preparation (EP) formulation is an attractive strategy to accelerate the formulation development of new chemical entities for first entry into human study. In this work, an EP suspension formulation for a development drug candidate GDC-6599 was successfully developed. The formulation spanned a wide concentration range from 0.1 to 2.0 mg/mL. A non-solubilizing vehicle, 0.6 % (w/v) methylcellulose solution was used to suspend GDC-6599. An aversive agent denatonium benzoate at an extremely low level (6 ppm) was applied as a taste masking agent. This enabled a simple matrix for the analysis of related substances from GDC-6599 during all stability studies. Microcrystalline cellulose at 10 mg/mL concentration was added to the EP formulation to generate a suspension appearance, leading to the success of using a single placebo for matching active formulation at all concentrations. The developed formulation demonstrated excellent homogeneity, sufficient stability and passed microbiological enumeration test. Rinsing performance test demonstrated that greater than 99.8 % amount of drug was successfully recovered by rinsing with water twice, providing guidance for clinical dosing. Biopharmaceutical assessment was conducted by both in silico simulation and in vitro tests. Greater than 90 % bioaccessibility of the EP suspension formulation was obtained via an in vitro system mimicking the human gastrointestinal absorption, consistent with the result from the in silico modeling. The developed EP formulation was successfully used to support the early single ascending dose (SAD) cohorts of GDC-6599 Phase I clinical study. The formulation matrix and assessment workflow developed in this work are generalizable as a platform for EP formulation development of new chemical entities for early phase clinical studies.

Pairwise approach for analysis and reporting of child's free sugars intake from a birth cohort study.

OBJECTIVES: The prospective cohort design is an important research design, but a common challenge is missing data. The purpose of this study is to compare three approaches to managing missing data, the pairwise (n = 1386 children), the partial or modified pairwise (n = 1019) and the listwise (n = 546), to characterize the trajectories of children's free sugars intake (FSI) across early childhood. METHODS: By applying the Group-based Trajectory Model Technique to three waves of data collected from a prospective cohort study of South Australian children, this study examined the three approaches in managing missing data to validate and discuss children's FSI trajectories. RESULTS: Each approach identified three distinct trajectories of child's FSI from 1 to 5 years of age: (1) 'low and fast increasing', (2) 'moderate and increasing' and (3) 'high and increasing'. The trajectory memberships were consistent across the three approaches, and were for the pairwise scenario (1) 15.1%, (2) 68.3% and (3) 16.6%; the partial or modified pairwise (1) 15.9%, (2) 64.1% and (3) 20.0%; and the listwise (1) 14.9%, (2) 64.9% and (3) 20.2% of children. CONCLUSIONS: Given the comparability of the findings across the analytical approaches and the samples' characteristics between baseline and across different data collection waves, it is recommended that the pairwise approach be used in future analyses to optimize the sample size and statistical power when examining the relationship between FSI in the first years of life and health outcome such as dental caries.

Trajectories of child free sugars intake and dental caries - a population-based birth cohort study.

OBJECTIVES: To investigate the association between trajectories of free sugars intake during the first five years of life and dental caries experience at five years. METHODS: Data from the SMILE population-based prospective birth cohort study, collected at one, two and five years old, were used. A 3-days dietary diary and food frequency questionnaire were used to estimate free sugars intake (FSI) in grams. The primary outcomes were dental caries prevalence and experience (dmfs). The Group-Based Trajectory Modelling method was used to characterize three FSI trajectories ('Low and increasing'; 'Moderate and increasing'; and 'High and increasing'), which were the main exposures. Multivariable regression models were generated to compute adjusted prevalence ratios (APR) and rate ratios (ARR) for the exposure, controlling for socioeconomic factors. RESULTS: The prevalence of caries was 23.3%, with a mean dmfs of 1.4, and a median of 3.0 among those who had caries. There were clear gradients of caries prevalence and experience by the FSI trajectories. The 'High and increasing' had an APR of 2.13 (95%CI 1.23-3.70) and ARR of 2.77 (95%CI 1.45-5.32) against the 'Low and increasing'. The 'Moderate and increasing' group had intermediate estimates. A quarter of the caries cases could have been prevented if the whole study sample had been in the 'Low and increasing' FSI trajectory. CONCLUSION: A sustained, high trajectory of FSI from a young age was positively associated with child dental caries. Measures to minimise consumption of free sugars must commence early in life. CLINICAL SIGNIFICANCE: The study has provided high level evidence to inform clinicians' decisions in promoting a healthy dietary pattern for young children.

A new species of Vietnamophryne (Anura: Microhylidae) from Northeastern Vietnam.

A new species of the genus Vietnamophryne is described from Vietnam on the basis of two specimens collected from Tuyen Quang Province, Northeastern Vietnam. The new species is morphologically most similar to Vietnamophryne occidentalis from Thailand, however, it differs from the latter by having large black blotches in the lower jaw region, and a yellow-orange chest and belly. The genetic distance between the new species and other Vietnamophryne taxa is > 2.13% (16S mtDNA gene fragment). Vietnamophryne aurantifusca sp. nov. can be distinguished from all other species of Vietnamophryne by a combination of the following morphological characteristics: Size medium (SVL 17.618.2 mm in males); head wider than long; tympanum medium; finger I longer than half of finger II; dorsal skin relatively smooth with some round nodules, concentrated in the middle of the back, arranged along the length of the back, with a prominent ridge along the spine; Dorsum orangish-brown entirely and paler on margin of back with a small brownish ridge along the spine; sides brownish with creamy patches and orange spots; ventral surface orange, with grey marbling, most intense on the throat, ventral side of arms and thighs, and ventral surfaces of limbs dark grey with some orange spots.

Group-based trajectories of maternal intake of sugar-sweetened beverage and offspring oral health from a prospective birth cohort study.

OBJECTIVES: To investigate the trajectory of maternal intake of sugar-sweetened beverages (SSB) during the first five years of their child's life and its effect on the child's dental caries at five years-of-age. METHODS: This is an ongoing prospective population-based birth cohort study in Adelaide, Australia. Mothers completed questionnaires on their SSB intake, socioeconomic factors and health behaviors at the birth of their child and at the ages of one, two and five years. Child dental caries measured as decayed, missing, or filled tooth surfaces was collected by oral examination. Maternal SSB intake was used to estimate the trajectory of SSB intake. The trajectories then became the main exposure of the study. Dental caries at age five years were the primary outcomes. Adjusted mean- and prevalence-ratios were estimated for dental caries, controlling for confounders. RESULTS: 879 children had dental examinations at five years-of-age. Group-based trajectory modeling identified three trajectories of maternal SSB intake: 'Stable low' (40.8%), 'Moderate but increasing' (13.6%), and 'High early' trajectory (45.6%). Multivariable regression analysis found children of mothers in the 'High early' and 'Moderate but increasing' groups to have greater experience of dental caries (MR: 1.37 (95%CI 1.01-1.67), and 1.24 (95%CI 0.96-1.60) than those in the 'Stable low' trajectory, respectively. CONCLUSION: Maternal consumption of SSB during pregnancy and in the early postnatal period influenced their offspring's oral health. It is important to create a low-sugar environment from early childhood. The results suggest that health promotion activities need to be delivered to expecting women or soon after childbirth.

Randomized controlled trial of pegylated interferon-alfa 2a and ribavirin in treatment-naive chronic hepatitis C genotype 6.

UNLABELLED: Hepatitis C virus (HCV) genotype is an important criteria in determining duration of therapy and predictor of sustained virologic response (SVR) to pegylated interferon (PEG IFN) and ribavirin (RBV) therapy. Optimal duration of therapy for patients with HCV genotype 6 is not known. We conducted a multicenter, open-label randomized controlled trial of patients with HCV genotype 6 at five gastroenterology clinics in the western U.S. Patients were stratified by viral load and histologic stage and assigned to receive PEG IFN-α2a 180 µg subcutaneously weekly and weight-based oral RBV 800 to 1,200 mg daily for 24 or 48 weeks. Primary outcome measurement was SVR rate by intention-to-treat analysis. From February 2005 to October 2007 a total of 60 patients (age 51 ± 10 years, 47% male, log HCVRNA 6.3 ± 1.1 IU/mL) were enrolled: 27 patients to 24 weeks and 33 patients to 48 weeks of therapy. In the 24-week and 48-week groups, 96% and 97% achieved early virologic response (P = 0.90); 89% versus 94% achieved end of therapy virologic response (P = 0.48). SVR was achieved in 70% versus 79% of patients assigned to 24 weeks versus 48 weeks (P = 0.45). Rapid virologic response (RVR) was a significant predictor of SVR in the 48-week group and trending towards significance in the 24-week group: 82% and 83% of those with RVR achieved SVR versus 33% and 29% for the 24-week and 48-week groups, respectively (P = 0.07 and P = 0.02). CONCLUSION: There was no significant difference in SVR rates in patients with HCV genotype 6 treated with PEG IFN-α2a and RBV for 24 versus 48 weeks.

Similar treatment response to peginterferon and ribavirin in Asian and Caucasian patients with chronic hepatitis C.

OBJECTIVES: Previous studies have found ethnicity to be an important predictor of outcomes of treatment with peginterferon (PEG-IFN) and ribavirin (RBV) in chronic hepatitis C. Although the expected sustained virological response (SVR) rates of Hispanics and African Americans are lower than those of Caucasians, SVR rates in Asians appear to be more favorable. However, in some of these studies, hepatitis C virus (HCV) genotype was identified by INNO-LiPA assay, which can mistype the easier-to-treat HCV genotype 6 as genotype 1. Our goal was to compare SVR rates among Caucasian and Asian-American patients with genotype 1 and 2/3 infection whose HCV genotypes were accurately classified by core sequencing testing. METHODS: A cohort of 269 consecutive treatment-naive HCV-infected patients with genotype 1 or 2/3 (157 Caucasians and 112 Asians) treated with PEG-IFN+RBV from January 2001 to November 2007 at four community-based gastroenterology clinics in Northern California were studied. The analysis of data was by intention-to-treat. RESULTS: The SVR rates for patients with genotype 1 were 45% for Caucasians and 52% for Asians (P=0.37). The SVR rates for patients with genotype 2/3 infection was 77% for Asians and 74% for Caucasians (P=0.7). On multivariate logistic regression analyses adjusting for age, alanine aminotransferase (ALT), baseline viral load, HCV genotype, and treatment adherence, we did not find Asian ethnicity to predict SVR. On a separate analysis, we found that Asians who had HCV genotype 1 or 1b by the less accurate INNO-LiPA assay had significantly higher SVR rates than Caucasians with genotype 1 (64% vs. 45%, respectively, P=0.03). CONCLUSIONS: SVR rates were similar in Asian Americans and Caucasians infected with HCV genotype 1 or 2/3 when HCV genotype classification was accurately determined.

Conductive resins improve charging and resolution of acquired images in electron microscopic volume imaging.

Recent advances in serial block-face imaging using scanning electron microscopy (SEM) have enabled the rapid and efficient acquisition of 3-dimensional (3D) ultrastructural information from a large volume of biological specimens including brain tissues. However, volume imaging under SEM is often hampered by sample charging, and typically requires specific sample preparation to reduce charging and increase image contrast. In the present study, we introduced carbon-based conductive resins for 3D analyses of subcellular ultrastructures, using serial block-face SEM (SBF-SEM) to image samples. Conductive resins were produced by adding the carbon black filler, Ketjen black, to resins commonly used for electron microscopic observations of biological specimens. Carbon black mostly localized around tissues and did not penetrate cells, whereas the conductive resins significantly reduced the charging of samples during SBF-SEM imaging. When serial images were acquired, embedding into the conductive resins improved the resolution of images by facilitating the successful cutting of samples in SBF-SEM. These results suggest that improving the conductivities of resins with a carbon black filler is a simple and useful option for reducing charging and enhancing the resolution of images obtained for volume imaging with SEM.

Nanoparticle formulation enhanced protective immunity provoked by PYGPI8p-transamidase related protein (PyTAM) DNA vaccine in Plasmodium yoelii malaria model.

We have previously reported the new formulation of polyethylimine (PEI) with gamma polyglutamic acid (γ-PGA) nanoparticle (NP) to have provided Plasmodium yoelii merozoite surface protein-1 (PyMSP-1) plasmid DNA vaccine with enhanced protective cellular and humoral immunity in the lethal mouse malaria model. PyGPI8p-transamidase-related protein (PyTAM) was selected as a possible candidate vaccine antigen by using DNA vaccination screening from 29 GPI anchor and signal sequence motif positive genes picked up using web-based bioinformatics tools; though the observed protection was not complete. Here, we observed augmented protective effect of PyTAM DNA vaccine by using PEI and γ-PGA complex as delivery system. NP-coated PyTAM plasmid DNA immunized mice showed a significant survival rate from lethal P. yoelii challenge infection compared with naked PyTAM plasmid or with NP-coated empty plasmid DNA group. Antigen-specific IgG1 and IgG2b subclass antibody levels, proportion of CD4 and CD8T cells producing IFN-γ in the splenocytes and IL-4, IFN-γ, IL-12 and TNF-α levels in the sera and in the supernatants from ex vivo splenocytes culture were all enhanced by the NP-coated PyTAM DNA vaccine. These data indicates that NP augments PyTAM protective immune response, and this enhancement was associated with increased DC activation and concomitant IL-12 production.

A ferrocene nucleic acid oligomer as an organometallic structural mimic of DNA.

The design, synthesis and electrochemical behaviour of an oligomer consisting of linked thymine-functionalised ferrocene units are reported, which, as a so-called form of ferrocene nucleic acid (FcNA), acts as a structural mimic of DNA.