Tag Archives: Obeticholic Acid

Although our report mainly focuses on the generation of

Although our report mainly focuses on the generation of clinical-grade hESCs, transplantation safety is also a concern. For example, a 9-year-old boy was diagnosed with a glioneuronal neoplasm after being transplanted with neural stem Obeticholic Acid derived from two donors (Amariglio et al., 2009). Although we did not observe any teratoma formation in the animal brain, more data are required to define the safety of these cells for the treatment of PD. Banking of clinical-grade hESCs is necessary for stem cell-based therapies (Lin et al., 2009). Once a clinical-grade cell line has been proved eligible based on its characteristics and biosafety according to existing international and national regulations, it should be stored in at least three sublevels of cell banks (master cell bank, seed cell bank, and working cell bank). The implementation of the International Stem Cell Banking Initiative (ISCBI) attempts to harmonize banking, and a study has been released to develop best practices for ensuring the quality of clinical-grade pluripotent stem cells (Andrews et al., 2015). Storing a sufficient number of clinical-grade hESC lines in a stem cell bank is necessary to meet the demands of hESC-based cell therapies in the future.

Experimental Procedures
All reagents used for clinical hESC derivation and differentiation are shown in Table S2.

Author Contributions

The authors are grateful to Elise Stewart and Siti Abdul Rahim for their revision of the grammar of the manuscript. This work was supported by the China National Basic Research Program (2013CB967100, to L.L.) and the National Key Research and Development Program of China-Stem Cell and Translational Research 2016YFA0101502 (to L.W.).

Uterine epithelia play key roles in sperm migration, embryo implantation, and fetal nutrition through their physiological functions in nutrient synthesis and transportation (Jeong et al., 2010). Traumatic injury or infection of the endometrium (Al-Inany, 2001), pre-pubertal exposure to hormones such as progesterone (Filant et al., 2012), and dysregulation of the uterus (Dahm-Kahler et al., 2016) could cause absence of uterine glandular epithelia in adulthood and even infertility (Kobayashi and Behringer, 2003). Uterine epithelial adenogenesis begins postnatally, involving budding, tubulogenesis, coiling, and branching of luminal epithelia (Gray et al., 2001). Mechanisms orchestrating these processes are complex. Only a few genes were reported to be involved in the development of uterine epithelia (Kobayashi and Behringer, 2003). It is important to systematically map the molecular and cellular dynamics during early gland development.
Stem/progenitor cells have been reported to be responsible for tissue development and homeostasis, while dysregulation of tissue-resident stem cells may result in dysplasia or diseases (Berry et al., 2016). Evidence for the existence of endometrial epithelial stem cells has been reported recently (Chan et al., 2004; Maruyama, 2014), but little is known about epithelial stem cells during development of the uterus. In-depth understanding of uterine epithelial stem cells could facilitate the development of alternative strategies to manipulate and treat uterus-associated diseases such as dysregulation of the window of implantation and Asherman\’s syndrome (Dahm-Kahler et al., 2016).
Single-cell analysis technologies have been increasingly utilized to identify rare cell subpopulations (Lanctot, 2015). In this study, single-cell RNA sequencing (RNA-seq) was applied to uterine epithelial cells at five developmental stages, ranging from neonatal to mature stages, to characterize the transcriptional profiles of single cells and to analyze the molecular and cellular dynamics during development of mouse uterus.



Experimental Procedures

Author Contributions

This work was supported by the National High Technology Research and Development Program of China (2016YFC1100401) (863 Program, 2015AA020302), the National Natural Science Foundation of China (CN) (81270682, 81300454), the Key Scientific and Technological Innovation Team of Zhejiang Province (2013TD11), China Postdoctoral Science Foundation (2015M571887), Zhejiang Medical and Health Science and Technology plan project (2013KYB080), and the Fundamental Research Funds for the Central Universities (2014QNA7016). We acknowledge Weiwei Yi from HangZhou Normal University for assistance in FACS sorting of cells. We acknowledge Kim Bunpetch for correcting grammatical errors.

br Conclusions br Acknowledgements br Introduction Poor diet



Poor diet is an important modifiable contributor to many chronic diseases including childhood obesity (Han, Lawlor, & Kimm; World Health Organization, 2004). Understanding the determinants of dietary behaviour during childhood is important as poor dietary behaviours track from childhood to adulthood (Craigie, Lake, Kelly, Adamson, & Mathers, 2011). Children\’s diet is influenced by individual preferences as well as the wider shared family, social and physical environment, as highlighted by ecological models of health behaviour (Bronfenbrenner, 1997). The contribution of the local food environment to a poor diet is a relatively new area of research. To date, findings are inconsistent and this may be due to conceptual and methodological issues associated with measuring the food environment (Caspi, Sorensen, Subramanian, & Kawachi, 2012; Feng, Glass, Curriero, Stewart, & Schwartz, 2010; Holsten, 2009; Mackenbach et al., 2014).
The food environment is multidimensional (Glanz, Sallis, Saelens, & Frank, 2005) and the availability of food outlets is one important aspect of the local food environment. Research has found that smaller food outlets including convenience stores tend to stock a higher proportion of processed foods, a smaller range of Obeticholic Acid and vegetables, and charge higher prices for food than supermarkets, especially in poorer areas (Kaufman, MacDonald, Lutz, & Smallwood, 1997; MacDonald & Nelson, 1991; Rose & Richards, 2004). Shorter distances to a supermarket and a higher number of local supermarkets are consistently associated with a higher dietary quality in North America, particularly among low income households (Rose & Richards, 2004). Evidence from Europe and Australia is less consistent (Black, Moon, & Baird, 2013) with recent studies finding no difference in food availability between better and worse off communities (Cummins & Macintyre, 1999, 2002), particularly for supermarkets (Maguire, Burgoine, & Monsivais, 2015).
Research on the association between the food environment around children\’s homes and diet is sparse and inconclusive. Engler-Stringer, Le, Gerrard, and Muhajarine (2014) conducted a systematic review which examined the influence of location and accessibility of food outlets on children\’s diet (). Though there was much heterogeneity between studies, the review found some moderate evidence to suggest that the local food environment around households may influence children\’s diet. However, the effect sizes in many of the included studies were small (Engler-Stringer et al., 2014). For example, a study from the UK reported that increasing distance to a convenience store was associated with a slightly lower intake of foods such as chocolate and crisps (Skidmore et al., 2010). Furthermore, in the UK, availability of ‘unhealthy’ food outlets was associated with a higher body mass index (BMI) which is a more distal outcome than diet (Jennings et al., 2011). Leung, Gregorich, Laraia, Kushi, & Yen, 2010 reported an inverse association between the prevalence of food/retail destinations in the neighbourhood environment and total energy intake in girls aged 6–8 years from the USA (Leung et al., 2010). However, there have also been null findings for the association between the local food environment and diet in children (An & Sturm, 2012).
Increasingly, policymakers recognise the potential role of the food environment to curb chronic diseases including obesity and also to encourage healthy eating. Thus, a better understanding of the relationship between local area food availability and dietary quality in children is needed. In 2007, 89% of all eating occasions for Irish children aged 5–12 years occurred at home (Burke et al., 2007) suggesting that food availability around households is important. For the current paper, we hypothesised that greater access to food outlets (closer proximity and the number of supermarkets) would be associated with a higher dietary quality in children. As children may have limited autonomy over food purchase and eating behaviours, we control for family level socio-economic factors to capture aspects of the shared home environment. This paper explores if distance to and the number of food outlets (supermarkets and convenience stores) in the local environment around households are associated with dietary quality in a nationally representative sample of nine year old children controlling for family level socio-economic factors.

The following are the supplementary data

The following are the supplementary data related to this article.

Funding Sources
This study is supported by the National Natural Science Foundation of China (NSFC31570497, 31322003, 31270152). The funding sources had no role in the study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the paper for publication.

Conflicts of Interest

Author Contributions


Nasopharyngeal carcinoma (NPC) is an uncommon malignancy with distinct geographic and ethnic characteristics. GLOBOCAN estimates that approximately 86,700 new cases of NPC have been reported, leading to an estimated 50,800 deaths in 2012 (Torre et al., 2015). NPC occurs frequently, with an incidence rate of 15 to 50 per 100,000 people annually in Southeast Asia. However, the incidence rate is not higher than 1 per 100,000 people in Western countries (Zhou et al., 2007; Yu and Yuan, 2002). Unfortunately, distant metastasis is a main cause of death for NPC patients, which often has an unfavorable prognosis (Chen et al., 2012; Chua et al., 2012; Liu et al., 2003). Although computed tomography (CT) and magnetic resonance imaging (MRI) are effective, they cannot accurately provide a prognosis for NPC or predict the effectiveness of biological therapeutic targets (Lin et al., 2013; Gong et al., 1991). Thus, a novel, noninvasive low-cost biomarker for early detection of NPC is of great importance to clinical practice.
DNA methylation, which is a common mechanism in epigenetic alterations, may be correlated with NPC (Jiang et al., 2015; Nawaz et al., 2015a). Promoter methylation of tumor suppressor genes (TSGs), such as calcium channel voltage-dependent alpha 2/delta subunit 3 (CACNA2D3) and cadherin 4 (CDH4), may play a crucial role in NPC development and progression (Wong et al., 2013; Du et al., 2011). Localized in human chromosomal region 3p21.3, the RAS association domain family protein 1A (RASSF1A) is an important TSG involved in multiple biological functions, including Obeticholic Acid regulation, microtubule stabilization, and apoptosis (Allen et al., 2007; Agathanggelou et al., 2005; Burbee et al., 2001). In NPC, RASSF1A gene expression is often blocked due to promoter methylation (Wang et al., 2009; Fendri et al., 2009; Lo et al., 2001). RASSF1A promoter methylation can be detected in tissue, brushing and blood samples of patients with NPC (Nawaz et al., 2015b; Yang et al., 2015; Hutajulu et al., 2011).
However, there are some inconsistencies in reports on the level of the RASSF1A promoter methylation in NPC. For example, Chang et al. reported that the rate of RASSF1A promoter methylation in NPC patients was different in tissue (66.7%), blood (3.3%), and brushing samples (33.3%) (Chang et al., 2003). Yang et al. reported that the RASSF1A promoter region was frequently methylated in 68.8% of brushing samples from NPC patients (Yang et al., 2015). Therefore, the aim of this study was to assess the relationship between RASSF1A promoter methylation and NPC risk in tissue, brushing, and blood samples. Moreover, we analyzed the correlation of RASSF1A promoter methylation with clinicopathological features of patients with NPC. Finally, we determined the diagnostic utility of RASSF1A promoter methylation as a noninvasive biomarker in samples of tissue, brushings, and blood.

Materials and Methods


Multiple factors are involved in NPC pathogenesis, including the Epstein-Barr virus, environmental, genetics and epigenetic components (Tsao et al., 2014; Lo et al., 2004). RASSF1A is a key TSG in various human cancers (Donninger et al., 2007). DNA methylation of TSG promoters leads to dysfunction or loss of gene expression, including RASSF1A, which may play a key role in the development of NPC (Fendri et al., 2009; Kong et al., 2006; Lo et al., 1996). Numerous studies with small populations have indicated that the frequency of RASSF1A promoter methylation is significantly increased in NPC tissue samples compared with non-tumor tissue samples (Nawaz et al., 2015b; Challouf et al., 2012; Wang et al., 2009; Fendri et al., 2009). Our results, comprised of 11 studies forming a large population, confirm that RASSF1A promoter methylation was notably more common in NPC compared with non-tumor tissues, which indicates that methylation of the RASSF1A promoter is closely linked to NPC tumorigenesis.

br Modeli http www GENS BIO COM

Modeling of DC motor
The DC motor is the obvious proving ground for advanced control algorithms in electric drives due to the stable and straight forward characteristics associated with it. It is also ideally suited for trajectory control applications. From a control systems point of view, the DC motor can be considered as SISO plant, there by eliminating the complications associated with a multi-input drive system [5].

Adaptive neuro-fuzzy mode speed controller

Simulation results of speed neuro-fuzzy controller
An adaptive neuro fuzzy inference system (ANFIS) controller is simulated for chopper-fed DC motor drive with parameters as shown in Table 2. The model chosen here for simulation and is taken from [8], where it is simulated and compared to the conventional PI controller. The second section discusses the comparison between conventional PI controller (speed controller), fuzzy self tuning PID (FPID) controller (where the conventional PI controller (speed controller) in the chopper-fed DC motor drive was replaced by the self tuning PID controller) [12] and (ANFIS) controller as shown in Fig. 7. The third and last section discusses the effect of increasing temperature on armature resistance of DC motor [13] and its impact on speed (Fig. 8).

Speed controller system based on (ANFIS) controller has been successfully developed using MATLAB (2009) to control the speed of a separately excited DC motor. This paper Lies in the application of (ANFIS) controller to control a separately excited DC motor. This paper also discusses the effect of increasing temperature on armature resistance of DC motor and its impact on speed. The performance of the system has been compared with conventional PI controller and fuzzy self tuning PID controller. An improved speed response has been achieved with the ANFIS than the other techniques mentioned. The performance has been tested by simulations. There is a Obeticholic Acid in number of ripples as well as steady state error and rise time and no overshoot appears. Moreover ANFIS controller regulates the speed in time less than previously mentioned controllers and FPID controller as shown in Table 3.
Actually, the proposed ANFIS speed controller improves the performance in both transient and steady state response in comparison to the conventional PI controller as shown in Tables 3 and 4.

A mechanism driven by a PMSM is today the most widely used due to the advantageous merits of cost, reliability, and performances. The PMSM is characterized by complex, highly non-linear, time varying dynamics, inaccessibility of some states and output for measurements and hence can be considered as a challenging engineering problem [1]. Some control techniques such as nonlinear control [2,3], sliding mode control [4] and intelligent control [5–7] have been developed to overcome these problems for speed and position control of the PMSM drive.
Fuzzy logic controllers (FLCs) have been used in many areas after fuzzy set theory was first introduced by Zadeh [8]. Fuzzy control (FC) does not need a mathematical model and is more insensitive to plant parameter variations and noise disturbance. Classically, fuzzy variables have been adjusted by expert knowledge. However, the design of FC has relied on trial and error. In practice, a precise knowledge of the plant of the complex systems is often difficult to obtain. So an efficient FC cannot be expected [9]. In recent years, to tackle this problem, the attractive approaches are provided by the neural networks. Generally, this control strategy is called as neuro-fuzzy controllers (NFCs). A NFC is suitable for control of systems consisting of uncertainties and nonlinearities. Although the NFC approaches can also achieve self-learning, it is inappropriate for on-line learning real-time control, since the learning process is time-consuming [10–12].
In addition, the fuzzy rules number will influence the controller accuracy and implementation consideration. Recently, some researchers propose the design methods of fuzzy control system based on sliding-mode approach. These approaches are referred to as fuzzy sliding-mode control (FSMC) design methods. By defining the sliding surface as the input variable of fuzzy inference rules, the number of fuzzy rules can be reduced to a minimum number. In this way, the chattering came out along the sliding surface is solved by FC Huang et al. [13].

Second Medicare also has a proxy poverty

Second, Medicare also has a proxy poverty measure. Many Medicare beneficiaries qualify for benefits from Medicaid, a Federal-State program for certain low-income individuals. In addition, Medicare “Buy-in” benefits were created to help low-income Medicare beneficiaries pay Medicare premiums, and in some instances, deductibles and copayments. Medicare Buy-in Programs are administered by States to pay all or part of Medicare health insurance co-pay expenses for eligible low-income Medicare recipients. All Medicare beneficiaries qualifying for either Medicaid or State Buy-in programs meet designated low-income standards, usually no higher than 135% of Federal poverty levels (Eichner & Vladeck, 2005; Ryan & Super, 2003). In 2013, $15,510 annual income was the poverty level for a US family of two (US HHS, 2013). Average income for households headed by someone≥65 years at that time was $53,000. Consequently, anyone receiving a Buy-in subsidy (dual eligibility) had an income less than one-third the average for elderly persons.
In addition to direct SES and disability measures, Medicare beneficiary data are linkable to claims data, permitting calculation of health status based on hospitalizations (Waxman, Greenberg, Ridgely, Kellermann, & Heaton, 2014).



Poverty is a critical problem, associated with impaired health and increased mortality, both US and worldwide (Isaacs & Schroeder, 2004). Poverty, ill health and mortality combine to form a vicious Obeticholic Acid harming a substantial proportion of the population. Currently intense debate exists regarding best approaches to alleviating US and worldwide poverty and its deleterious effects on health.
Previous studies demonstrated elderly and younger US Blacks consistently have higher mortality rates than Whites. Reasons suggested to explain this disparity include differences in health status (Hernandez & Pressler, 2014), access to care (Schoenbaum, Schoen, Nicholson, & Cantor, 2011), insurance coverage (Van Der Wees, Zaslavsky, & Ayanian, 2013), and biologic characteristics including prevalence of acute and chronic illnesses, as well as genetic variation (Rosenberg et al., 2010). All these factors may be exacerbated by poverty.
The higher mortality risk among Black Medicare beneficiaries was attenuated by accounting for several variables. Black beneficiaries had demonstrably worse health status, measured by Charlson score and ESRD prevalence. Adjusting for these factors together reduced the racial death rate disparity considerably. Black beneficiaries also had twice the rate of prior disability, accounting for further disparity reduction. However, it was poverty, measured by the State Buy-in indicator for the poor and near-poor, that had the greatest impact on accounting for the disparity between the two groups. The addition of this individual level variable essentially equalized the groups’ adjusted mortality rate. Secondary analyses showed inclusion of individual level poverty alone could account for the age-gender adjusted mortality difference between Black and White aged Americans (Fig. 2, Panel B).
The “adjusted” mortality advantage for Blacks does not mean elderly Blacks are better off than elderly Whites (Isaacs & Schroeder, 2004). Rather, it emphasizes the tremendous effect of the racial differential in poverty on health disparities. Elderly Blacks are three times as likely as elderly Whites to live in poverty, measured by Buy-in. These findings do however suggest the higher age–gender adjusted mortality rate among Blacks is explained by factors known to affect health, such as disability, comorbid illness, access to advanced care, employment, and primarily the notable extent of poverty in this population (Isaacs & Schroeder, 2004).
Poverty, as represented by Buy-in or dual eligibility, clearly explains much of the disparity in mortality rates between Black and White people in Medicare, which represents the universe of US aged persons with health insurance. Reducing poverty, or alleviating its adverse effects, is a daunting challenge. Methods to alleviate poverty include policy approaches such as improving neighborhood characteristics, increasing health care coverage through Medicaid and the Affordable Care Act, supplementing diet and income through the food stamp program, and improving income of the poor and near-poor through the earned income tax credit. Other interventions include consideration of innovative approaches such as housing initiatives and various health interventions (Doran, Misa, & Shah, 2013; Ludwig et al., 2011). However, poverty will likely remain a vexing problem, especially in light of increasing income disparities (Granados, 2013; Isaacs & Schroeder, 2004).

The maintenance of river water quality is controlled under

The maintenance of river water quality is controlled under the EU Water Framework Directive (2000/60/EC) for which waterbody-specific targets are stipulated in terms of ecological status. In England and Wales, the EA is the designated competent authority charged with monitoring, reporting and enforcement, while for Scotland it is SEPA, where the WFD is legislated under the Water Environment and Water Services (Scotland) Act 2003 (WEWS act). Identification of reasons for failure and programmes of measures to rectify non-conformity is undertaken in iterative cycles. Nationally around 75% of waterbodies currently fail to meet good ecological status although the situation is improving (Priestley, 2015). Urban influences may be Obeticholic Acid in governing the condition of waterbodies (e.g. effluents), especially in small waterbodies (McGrane et al., 2016). In this regard, control of hazardous substances through wastewater treatment and improvements to sewerage infrastructure are commonly implemented measures.
Climate projections for the UK are provided by the latest generation of the UK Met Office Hadley Centre regional climate model (RCM) projection scenarios − UKCP09 − and indicate the 21st C will have wetter, warmer winters (mainly to the north and west) and hotter, drier summers (mainly in the south and east) but with variable change predicted under emission scenarios and probability level (Murphy et al., 2010 − Fig. 1). This spatial and temporal variability across a relatively small island nation is not shown in global climate models (IPCC, 2014) and exemplifies why it is important to consider climate change at refined spatial and temporal scales using RCMs when assessing impacts on hydrological processes within relatively small (by international standards) catchments and defined urban areas.

Urban flooding: current and future pressures

Urban water quality: current and future pressures
River water quality, both chemical and biological, was until 2009 monitored and assessed using the General Quality Assessment (GQA) scheme. Data showed a general improvement (Fig. 5) in rivers exhibiting good or excellent chemical and biological quality (EA, 2013). Since 2009 the classification scheme introduced by the Water Framework Directive (WFD) standards have been in place, and in 2009 26% of water bodies in England met Good Ecological Status (the requirements for viable ecosystems), decreasing to 25% in 2012. Whilst significant effort has been made in reducing agricultural, point source and industrial pollution there remains increasing pressure from urban diffuse pollution Obeticholic Acid which is responsible for 49% of failures to water quality targets (Defra, 2012). Major pollution events in UK urban rivers are primarily a result of partially treated sewage being discharged during storm events (Ellis, 1991).

Confidence assessment of evidence
This section provides a confidence assessment of the reviewed literature in providing evidence of a direction of change or response in urban flooding and urban water quality as a result of urbanisation and climate change. In order to assess the confidence of reported projected changes a level of confidence has been ascribed to the overall direction of change for each topic (Table 1). This is based upon a confidence matrix Antiparallel reflects both the amount of evidence and the degree of agreement. Such confidence assessments were developed and employed when evaluating evidence in the IPCC AR5 (Mastrandrea and Field, 2010) and climate change impact report cards for the UK (e.g. Hannah and Garner, 2013). Topics assessed as having HIGH confidence evidence are those with numerous sources of evidence with results in agreement, MEDIUM confidence is ascribed where there is limited evidence but results are in agreement, while LOW confidence is ascribed where only isolated or inferred evidence was available. The confidence ascribed should only be taken as indicative of the state of current knowledge and direction of change, not the quality of evidence. For such an assessment a systematic review would be required.

It is suggested that effect size

It is suggested that effect size of this SNP is greater in males. Indeed, sexual differences in the regulation of serum UA levels have been reported. Obesity is often accompanied by hyperuricemia, but few studies have addressed the association between obesity and genetic variants involved in UA metabolism. The degree of association between ABCG2 rs2231142 SNP and gout risk has been found to vary with ethnicity. In this study, we examined whether association between the ABCG2 SNPs and UA levels in a Taiwanese cohort is differentially regulated by sex and obesity.

Materials and methods


We confirmed association of the SNP rs2231142 with UA levels and hyperuricemia in a Taiwanese cohort, and found it predominantly in males. Furthermore, obesity alone determined serum UA levels regardless of ABCG2 genotypes or sex, and we were the first to find an association between the rs2231142-A allele and hyperuricemia in obese patients.
A previous study shows that serum UA concentration has a 63% heritability. Indeed, a meta-analysis identifies ABCG2 among nine loci associated with UA concentration. In these studies, rs2231142 is the only SNP consistently associated with both hyperuricemia and gout. We confirmed the association with hyperuricemia except in nonobese females.
Previous studies show substantial interaction between genotypes and sex on UA levels. For instance, rs2231142 is consistently associated with UA concentration and gout in males. Our data showed a similar interaction, as we found significant association between rs2231142 and UA levels in males.
We found significant association between rs2231142 and hyperuricemia in obese patients. In a mouse model of obesity, concentration of both ABCG2 and urate Obeticholic Acid transporter URAT1 increases significantly, suggesting a link between enhanced urate reabsorption and obesity-associated hyperuricemia. Although we did not measure ABCG2 or URAT1 concentration, UA concentration was higher in obese patients and was further enhanced in those carrying the rs2231142-A allele. We hypothesized that obesity readily reveals effect of rs2231142 on hyperuricemia.
We uncovered an extra layer of interaction between sex, obesity, and rs2231142 on UA levels. Our data showed rs2231142-A was not associated with UA levels in nonobese females. This difference might be due to specific physiological characteristics of the nonobese females other than that of estrogen, because it has been reported that estrogen does not increase renal clearance of serum UA in adult women. Regarding the female hormonal effect on UA levels, we did not observe significant differences between premenopausal and menopausal female subgroups (Supplementary Table 1). Alternatively, nonobesity may have ameliorated hyperuricemia in rs2231142-A-carrying females by compensating for reduced ABCG2 activities. Whether it is due to metabolic or additional hormonal effect awaits further investigation, and a larger sample size is needed to clarify the role of sex hormones on UA levels and hyperuricemia in female patients.

Because of the relatively small sample size and high minor allele frequency of rs2231142 in this study (Supplementary Table 2), it might have had limited power to detect associations between rs2231142 and UA. Still, we were able to validate our results independently using multiple regressions adjusted for confounding factors (Supplementary Table 3). In addition, we also validated our results using multiple testing corrections including full scan permutations (p = 0.001 for 1000 permutations), Bonferroni adjustment and false discovery rate (FDR) calculations (rs2231142-C allele; both regression Bonferroni P and regression FDR = 5.7 × 10−4), thus strengthening the conclusion that rs2231142 is indeed associated with serum UA levels.

A reduction-of-function SNP rs2231142 in the ABCG2 gene is associated with hyperuricemia in a Taiwanese cohort. The genetic determinants Obeticholic Acid for hyperuricemia differ according to sex and obesity status. The rs2231142-A allele has significantly stronger association with hyperuricemia in male and obese patients.

Obeticholic Acid The zirconia substrate was not sandblasted

The zirconia substrate was not sandblasted before coating or infiltration as performed in previous studies [23], [24] and [25]; this was to exclude further variability, but assess only the potential effects of proposed treatments. The need for sandblasting prior to usage of organo-metallic precursors might be considered a drawback of the technique once it has been reported that air-abrasion could affect long-term reliability of oxide ceramics [26].
Overall, INF method attained lower initial bonding potential compared to COA method. These outcomes might be attributed to a less homogeneous surface coating, as observed in SEM analysis, and less silica present on zirconia surface (Fig. 4C and D). Application of organo-metallic precursor solutions before zirconia sintering (INF method) could theoretically improve coating retention to ceramic structure since precursors and zirconia frame sintering occurs simultaneously; hence better physical entanglement of silica layer and zirconia would be expected. However, INF method seems to be more sensitive to processing variables, as uncoated areas or areas inconsistently coated were often observed.
A μ-Raman analysis (data not shown) was also conducted in an attempt to investigate the thickness and in-depth homogeneity of silica layer. The analysis was conducted up to 10 μm deep into coating layer and failed to identify any significant differences in silica concentration. It is postulated that coating had a thickness above 10 μm, though further investigation is required to assess actual thickness of silica coat deposited on zirconia by methods proposed in this study. This information is essential since it may interfere with Obeticholic Acid of ceramic structure on abutment teeth clinically in case a very thick silica layer is formed. It is also expected that silica coating thickness may be controlled by concentration of organometallic precursors used in treatment solution as well as through the volume of solution used. Further techniques such as spin-coating or dip-coating, despite showing great efficiency in control of film thickness, would be difficult to reproduce in laboratory and clinical applications.
Previous studies proposed silica films deposition on zirconia by magnetron sputtering in a custom-made vacuum chamber using a target of ultra-pure Si [27] and [28]. Although this technique is different from methods presented in this study, the morphology of silica layer formed as well as improved adhesion to zirconia were very similar to those observed in the present study. By comparison however, the present methods seem to be simpler and more feasible for application in dental laboratories.
An additional issue concerning the technology proposed whether INF method could significantly affects structural integrity and sintering cycle of zirconia. From a structural point of view, INF method is somewhat audacious as it could alter the environmental conditions to which zirconia is subjected and also its mechanical properties. Studies evaluating dynamic and static mechanical strength should be performed in future investigations to clarify this condition. Notably, COA method appears to address the problem of yielding adhesion to zirconia ceramic clearer by using an easy and economical approach. In fact, this technique may be a feasible alternative to deposit silica onto zirconia in laboratory to improve subsequent adhesion with methacrylate-based materials. Furthermore, clinical studies are needed before broad indication of the techniques proposed in this study in order to assess their actual effectiveness, since any in vitro study has a number of limitations in predicting clinical performance of materials and techniques.
5. Conclusion
Present study introduces a novel, simple, and cost-effective method to provide adhesion of methacrylates to yttria-stabilized zirconia ceramic. The reagents used are safe, non-toxic, and reasonably inexpensive. The application technique used is also convenient as it demands same clinical and laboratory time employed in processing of oxide bioceramics. The sintering time and temperature used to process or glazing veneering ceramic could be used for SiOx condensation and networking when COA method is used, while sintering cycle of zirconia blocks could be used for INF method. Consequently, it may be concluded that experimental methods tested in this study may be useful alternative simplified low-cost approach to commercial tribochemical silicatization since they are able to provide a stable bond between resin cement and zirconia. The methods proposed could also allow bonding of other types of polymeric materials for varied applications of Y-TZP ceramics as biomaterials.