αE-catenin inhibits a Src-YAP1 oncogenic module that couples tyrosine kinases and the effector of Hippo signaling pathway.

Cell-cell adhesion protein αE-catenin inhibits skin squamous cell carcinoma (SCC) development; however, the mechanisms responsible for this function are not completely understood. We report here that αE-catenin inhibits ß4 integrin-mediated activation of SRC tyrosine kinase.SRCis the first discovered oncogene, but the protein substrate critical for SRC-mediated transformation has not been identified. We found that YAP1, the pivotal effector of the Hippo signaling pathway, is a direct SRC phosphorylation target, and YAP1 phosphorylation at three sites in its transcription activation domain is necessary for SRC-YAP1-mediated transformation. We uncovered a marked increase in this YAP1 phosphorylation in human and mouse SCC tumors with low/negative expression of αE-catenin. We demonstrate that the tumor suppressor function of αE-catenin involves negative regulation of the ß4 integrin-SRC signaling pathway and that SRC-mediated phosphorylation and activation of YAP1 are an alternative to the canonical Hippo signaling pathway that directly connect oncogenic tyrosine kinase signaling with YAP1.

Comparison of flexural strength, marginal gap, and internal fit of milled and 3D-printed crown materials.

The purpose of this study was to compare the flexural strength, Weibull modulus (reliability), marginal gap, and internal fit (internal gap) of 4 materials for milling or 3-dimensional (3D) printing of definitive and provisional crowns: IPS e.max CAD (IEC), Paradigm MZ100 Block (PMB), Permanent Crown Resin (PCR), and Temporary CB Resin (TCR). Flexural strength was tested by subjecting sectioned milling blocks (IEC and PMB) or 3D-printed bars (PCR and TCR) to a 3-point bending test in a universal testing machine (n = 15 per material). Crowns were milled or 3D printed, and the marginal gap and internal fit were measured using microcomputed tomography (n = 5 per material). The data were analyzed with a t test and compared using analysis of variance (ANOVA) with Tukey post hoc comparisons (α = 0.05). The groups demonstrated the following mean (SD) flexural strength values: IEC, 335.50 (28.97) MPa; PMB, 154.34 (21.03) MPa; PCR, 128.09 (7.30) MPa; and TCR, 126.29 (9.23) MPa. A 1-way ANOVA revealed significant differences in the flexural strengths of sectioned and 3D-printed bars (P < 0.001). The PMB group showed the lowest Weibull modulus (8.77), indicating its poor reliability. The IEC group showed the smallest marginal gap, 53.42 (31.99) µm; this value was significantly smaller than the gap in the TCR group (P < 0.001) but not the PCR or PMB group. The PMB group had the smallest internal fit discrepancy (87.44 [37.60] µm) but was not significantly different from PCR, while TCR had a significantly greater internal fit discrepancy (130.61 [65.16] µm) than IEC, PMB, and PCR (P < 0.001). The occlusal internal fit discrepancies of 3D-printed crowns were significantly greater than those of milled crowns (P < 0.001). There was no statistically significant difference in flexural strength between the 3D-printed definitive (PCR) and provisional (TCR) materials. When the data were combined according to manufacturing method, the marginal gap and internal fit of crowns fabricated with 3D printing were comparable to those of milled crowns, and all mean marginal gaps were within a clinically acceptable limit of less than 120 µm.

In Vitro Microleakage and Fracture Resistance of "Infinity Edge" and Cusp Reduction Preparation Designs for Moderate-sized Class II Composites.

AIM: This study aimed to evaluate the marginal microleakage and maximum occlusal fracture loads and fracture modes of two novel class II preparation designs, "infinity edge" and the "2.5 mm cusp reduction" preparations as compared to a traditional class II preparation without cuspal involvement. MATERIALS AND METHODS: Thirty extracted human mandibular molars were prepared for moderate-sized class II restorations with extensions into all occlusal grooves. Of these, ten class II preparations served as control. Ten were modified for a 2.5 mm even reduction of the cusps adjacent to the interproximal box. An additional 10 preparations were modified with an "infinity edge" bevel on the interproximal and occlusal portions. All teeth were restored utilizing a flowable bulk-fill composite in the apical portion of the interproximal box and 2-4 mm of heated bulk-fill composite in one increment for the remainder. All groups were cyclic loaded and thermocycled, then imaged with microcomputed tomography (µCT) before and after infiltration with a silver nitrate solution. Images were subtracted to obtain volumetric measurements of microleakage and reported as a percentage of the total volume from the apical extent of the proximal box. All groups were loaded to failure and fracture load and mode were recorded. RESULTS: No significant differences were found in microleakage volume as a percentage of total tooth volume; however, the "infinity edge" group had significantly greater microleakage in the proximal box compared to the traditional class II group. No significant differences were found in fracture load or mode between the groups. CONCLUSION: Traditional class II, 2.5 mm cuspal reduction, and "infinity edge" preparation designs have similar fracture loads as well as volumes of microleakage; however, an "infinity edge" preparation has a higher ratio of microleakage in the proximal box. CLINICAL SIGNIFICANCE: Clinicians should carefully consider the use of "infinity edge" margins, particularly on dentin in the apical extent of the proximal box. How to cite this article: Watson JC, Lien W, Raimondi JC, et al. In Vitro Microleakage and Fracture Resistance of "Infinity Edge" and Cusp Reduction Preparation Designs for Moderate-sized Class II Composites. J Contemp Dent Pract 2024;25(1):3-9.

Novel chairside spectrometer-trained system for measuring the irradiance of light-curing units.

The purpose of this study was to compare the performances of 5 different instruments in measuring the irradiance of light-curing units (LCUs). A novel spectrometer-trained radiometer (CheckUp), 2 conventional chairside radiometers (Bluephase Meter I and Bluephase Meter II), and 2 devices considered to be gold standards for measuring irradiance (an integrating sphere spectrometer and a thermopile sensor) were used to evaluate 7 LCUs. The irradiance of each LCU was measured 10 times with each meter. Data were analyzed using linear regression analysis and a 1-way analysis of variance with Tukey post hoc test (α = 0.05). The mean irradiance values of the LCUs differed significantly depending on which meter was used for measurement (P < 0.05). Bivariate regression analysis demonstrated that the highest correlations in the irradiance values were found between the CheckUp meter and both the integrating sphere (r2 = 0.980) and the thermopile (r2 = 0.933). The absolute mean (SD) percentage deviation between irradiance measured by the CheckUp instrument and irradiance measured by the other meters was 7.2% (2.0%) for the integrating sphere, 7.0% (3.6%) for the thermopile, 21.5% (16.1%) for Bluephase Meter I, and 13.1% (7.1%) for Bluephase Meter II. Compared with the 2 conventional chairside radiometers, the CheckUp meter provided the highest correlation with and lowest absolute percentage deviation from the irradiance measured by the gold standard spectrometers.

Efficacy of a chairside extraoral suction system in the reduction of aerosol contamination.

The dental setting is regarded as a high-risk environment for aerosol concentrations and transmission of respiratory infectious agents, especially in relation to the COVID-19 pandemic. Although a number of approaches and practices have evolved to reduce the spread of pathogens in the dental setting, the risk of airborne infection remains a concern. Several new extraoral suction (EOS) devices have been marketed recently; further investigation is warranted to determine their clinical effectiveness. The aim of this study was to evaluate the efficacy of a chairside EOS device (PAX 2000 Extraoral Dental Suction System) in reducing aerosol contamination from patients receiving ultrasonic scaling by a registered hygienist as a part of initial or supportive periodontal therapy. The number of colony-forming units (CFUs) was measured with agar plates before, during, and after ultrasonic scaling at 3 different locations in the dental operatory (instrument table, patient chest area, and patient foot area). Forty subjects were randomly allocated into 2 test groups (n = 20) in which ultrasonic scaling was performed with or without the use of the EOS device. The CFUs retrieved after incubation were quantified and identified by their bacterial or fungal taxon. The use of the EOS device reduced the number of CFUs during scaling at all 3 locations, but the difference was only statistically significant (P = 0.018; Mann-Whitney U test) at the patient's chest area, where the highest number of CFUs was present. The aerosols consisted of 74 different taxa of human origin. The results suggest that the tested EOS system may reduce aerosol contamination in the clinical dental setting, especially in proximity to the patient's head, where most aerosols are generated.

Wnt some lose some: transcriptional governance of stem cells by Wnt/ß-catenin signaling.

In mammals, Wnt/ß-catenin signaling features prominently in stem cells and cancers, but how and for what purposes have been matters of much debate. In this review, we summarize our current knowledge of Wnt/ß-catenin signaling and its downstream transcriptional regulators in normal and malignant stem cells. We centered this review largely on three types of stem cells--embryonic stem cells, hair follicle stem cells, and intestinal epithelial stem cells--in which the roles of Wnt/ß-catenin have been extensively studied. Using these models, we unravel how many controversial issues surrounding Wnt signaling have been resolved by dissecting the diversity of its downstream circuitry and effectors, often leading to opposite outcomes of Wnt/ß-catenin-mediated regulation and differences rooted in stage- and context-dependent effects.

Hardness Development in Resin Composite Core Materials.

PURPOSE: To investigate the hardness characteristics of 13 contemporary resin core materials. MATERIALS AND METHODS: Specimens (n = 12) were fabricated using stainless steel molds with top surfaces of dual-cure products photopolymerized while additional groups were allowed to self-cure. Twelve Knoop hardness indentations 500 microns apart were obtained of photopolymerized top and bottom sample surfaces as well as the self-cured sample surface with the mean recorded as the representative sample hardness. Testing was completed at 10 minutes, 1 hour, and 24 hours. In addition, hardness values were compared to that obtained from polished coronal dentin samples. Mean data between groups were analyzed with Kruskal-Wallis/Dunn's, within groups with repeated measures ANOVA/Tukey's. RESULTS: Hardness results were material dependent. All but two products demonstrated a 0.8 bottom/top Knoop hardness ratio at 10 minutes. Product's self-cure cure reaction did not attain hardness similarity with any photopolymerized top surfaces and while some materials were found to have similar dentin hardness to resin top surface ratio similarity, only one product had hardness equal to or greater than that of dentin during any time period. CONCLUSIONS: Under this study's conditions, hardness development was material dependent and all but two products demonstrated adequate hardness-derived degree of cure assessment at 10 minutes after preparation. Self-cured samples demonstrated hardness increase; however, no self-cured material achieved hardness similarity to photopolymerized top surfaces. None of the materials achieved hardness similarity to dentin and only one product demonstrated hardness greater than that of dentin.

Efficacy of various decontamination methods and sterilization on contaminated and inoculated diamond-coated burs.

The objective of this study was to evaluate the efficacy of various decontamination methods and subsequent sterilization on contaminated and inoculated diamond-coated burs. One hundred forty new diamond-coated burs and 120 extracted human molars were utilized in this study. The burs were divided into 7 groups (n = 20): 1, positive control; 2, negative control; 3, new, unused burs; and 4 to 7, burs subjected to various combinations of cleaning methods (manual cleaning, use of a cleaning stone, and/or ultrasonic cleaning) after contamination. In all of the groups except group 3, the burs were sterilized and used to abrade the enamel and dentin of the sterilized extracted teeth. In groups 1 and 4 to 7, the burs were subsequently inoculated with 1 of the following microorganisms: Enterococcus faecalis (ATCC 19433), Staphylococcus aureus (ATCC 6538), Pseudomonas aeruginosa (ATCC 15442), or Geobacillus stearothermophilus (ATCC 7953). Twenty-four hours after inoculation, the burs in group 2 and groups 4 to 7 were subjected to the cleaning treatments and sterilized with steam. The burs in all 7 groups were then cultured for bacterial contamination. No growth of any bacterial type was observed in any of the groups except the positive control group. The use of a cleaning stone in combination with manual or ultrasonic cleaning resulted in the least amount of remaining tooth debris on the diamond-coated burs. The contaminated and inoculated diamond-coated burs tested in this study were successfully sterilized, and the tested bacteria were eliminated. If using a diamond-coated bur multiple times, practitioners should consider utilizing debridement with a cleaning stone followed by either manual or ultrasonic cleaning and then by a single cycle of steam sterilization.

Repair of resin-veneered polyetheretherketone after veneer fracture.

STATEMENT OF PROBLEM: If a composite resin-veneered polyetheretherketone (PEEK) restoration chips or fractures, a repair may be indicated. However, the most appropriate repair protocol for a composite resin-veneered PEEK restoration is unclear. PURPOSE: The purpose of this in vitro study was to determine the efficacy of airborne-particle abrasion and/or a primer in the repair of composite resin-veneered PEEK prostheses. MATERIAL AND METHODS: PEEK specimens (N=80) were airborne-particle abraded with alumina before being conditioned with a methyl methacrylate-based primer. A thin layer of opaquer was applied, and a split mold was then filled with a veneering resin. The specimens underwent 5000 thermocycles, and then shear bond strength (SBS) was determined and used as the positive control group. Specimens that failed in either mixed or adhesive modes were contaminated with saliva and then exposed to 4 different repair treatment methods: no airborne-particle abrasion, bonded without a primer (negative control group); airborne-particle abrasion, bonded without a primer; no airborne-particle abrasion, bonded with a primer; and airborne-particle abrasion, bonded with a primer. All specimens had opaquer applied before being veneered. Repaired specimens then underwent thermocycling before SBS testing. Data were analyzed via ANOVA with a Newman-Keuls post hoc test (α=.05). RESULTS: The SBS values for the negative control were significantly lower than those of all other repair groups and the control group (P<.018). No significant differences in the SBS values were found among these other repair groups or the positive control group (P>.05). CONCLUSIONS: Composite resin-veneered PEEK restorations or prostheses repaired with airborne-particle abrasion and/or primer can provide SBS comparable with that of the initial SBS.

DNA methylation dynamics during in vivo differentiation of blood and skin stem cells.

DNA methylation is a mechanism of epigenetic regulation that is common to all vertebrates. Functional studies underscore its relevance for tissue homeostasis, but the global dynamics of DNA methylation during in vivo differentiation remain underexplored. Here we report high-resolution DNA methylation maps of adult stem cell differentiation in mouse, focusing on 19 purified cell populations of the blood and skin lineages. DNA methylation changes were locus specific and relatively modest in magnitude. They frequently overlapped with lineage-associated transcription factors and their binding sites, suggesting that DNA methylation may protect cells from aberrant transcription factor activation. DNA methylation and gene expression provided complementary information, and combining the two enabled us to infer the cellular differentiation hierarchy of the blood lineage directly from genome-scale data. In summary, these results demonstrate that in vivo differentiation of adult stem cells is associated with small but informative changes in the genomic distribution of DNA methylation.

Early sexual initiation and risky sexual practices among alcohol- and tobacco-using young adults in Taiwan: mediation analysis of preceding-sex use of illicit drugs.

BACKGROUND: As early sexual initiation is increasingly common in East Asia, we examined its relations to risky sexual practices in alcohol- and tobacco-using individuals in Taiwan and evaluated whether the associations were mediated through preceding-sex use of illicit drugs. METHODS: Participants, recruited from alcohol- and tobacco-using adults aged 18 to 50 in Taipei through respondent-driven sampling (N = 1115), completed a computer-assisted self-interview covering questions on substance use and sexual experiences. In a subsample of 916 participants who had had sexual experience (median age 27), we examined the relations of early sexual initiation (< 16 years) to multiple sexual partners, casual sex, group sex, and rare condom use. Causal mediation analyses were conducted to examine whether illicit drug use preceding sex mediated these associations. RESULTS: Around 9.3% reported early sexual initiation and the prevalence of risky sexual practices ranged from 7% (group sex) to 47% (rare condom use). Early initiators had a higher prevalence of regular binge drinking, illicit drug use, and risky sexual practices. In the multivariable analyses, higher odds of multiple sexual partners, casual sex, and group sex were consistently associated with early sexual initiation, gender, and their interaction. Mediation through preceding-sex use of illicit drugs was found between early sexual initiation and the three risky sexual practices, with the proportions mediated ranging from 17 to 19%. CONCLUSIONS: Early sexual initiators were more likely to engage in risky sexual practices and preceding-sex use of illicit drugs partially explained this relationship, calling for more attention to this population's sexual health.

A Survey of US Air Force General Dentists Regarding Computer-aided Design/Computer-aided Manufacturing Usage.

AIM: The purpose of this study was to survey all United States Air Force (USAF) general dentists regarding their experience with computer-aided design/computer-aided manufacturing (CAD/CAM) while in a dental school. Dental school graduation year and location was compared to the type and amount of CAD/CAM training and clinical experience during dental school to better understand the differences and influence of this technology. MATERIALS AND METHODS: A survey consisting of six questions was sent through e-mail to 546 general dentists in the AF Dental Corps in 2018 of which 306 replied (56% response rate). RESULTS: Dentists who graduated in 2005 or earlier and between 2006 and 2009 stated they did not receive CAD/CAM training in dental school, while more respondents in the group of graduation years 2014-2017 stated that they did receive training. About 11% of the respondents who graduated in 2014-2017 completed 6-10 restorations and 9% completed 11 or more restorations compared to the other year groups. More respondents who graduated from a dental school in the southwest and southeast regions of the United States reported completing more restorations compared to other school regions. CONCLUSION: Computer-aided design/computer-aided manufacturing is now becoming a prevalent curriculum in US dental schools, both as a core requirement and an elective. Its training platforms varied from lectures and literature reviews to preclinical laboratory. CLINICAL SIGNIFICANCE: More respondents in the groups of graduation years 2014-2017 had completed more CAD/CAM restorations compared to other year groups; however, most of the respondents did not feel their training was sufficient enough to use CAD/CAM technology independently.

Assessing Flexural Strength Degradation of New Cubic Containing Zirconia Materials.

AIM: Newer zirconia materials may have greater strength degradation under cyclic fatigue with increased yttria and cubic content. The purpose of this study was to evaluate the flexural strength (FS) degradation of newer zirconia materials compared to more traditional tetragonal zirconia materials. MATERIALS AND METHODS: The following materials were tested: two 3 mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) materials (Lava Plus, 3M ESPE; Katana ML, Kuraray), one 4 mol% partially stabilized zirconia (4Y-PSZ) material (Katana STML, Kuraray), two 5 mol% partially stabilized zirconia (5Y-PSZ) materials (Katana STML, Kuraray; Lava Esthetic, 3M ESPE), and one lithium disilicate material (IPS e.max CAD LT, Ivoclar Vivadent). Thirty beams were milled for each ceramic material with final dimensions of 4.0 × 1.3 × 18.0 mm after sintering or crystallization. Each specimen was placed on a 3-point bend test device on a universal testing machine (Instron, Norwood, MA). Flexural strength was determined on 10 beam specimens per group with a central load applied until fracture. Flexural fatigue strength was then measured on the remaining 20 beam specimens per group using the staircase method for 6,000 cycles at 2 Hz. Data were analyzed with one-way ANOVAs/Tukey post hoc tests (α = 0.05). RESULTS: A significant difference was found between groups (p < 0.001) per property. The 3Y-TZP zirconia materials had the greatest flexural and flexural fatigue strength. The cubic containing zirconia materials performed more moderately. The lithium disilicate material had the lowest strength values. The percent degradation in flexural fatigue strength of the 3Y-TZP zirconia materials was less than the 5Y-PSZ, Katana UTML, and the 4Y-PSZ, Katana STML, cubic containing materials, but similar to the 5Y-PSZ cubic containing material, Lava Esthetic. CONCLUSION: The amount of strength degradation was material dependent, with the 4Y-PSZ or 5Y-PSZ cubic containing zirconia materials demonstrating greater or similar strength degradation compared to the primarily tetragonal 3Y-TZP zirconia materials. CLINICAL SIGNIFICANCE: The differences in FS degradation between cubic containing materials and traditional zirconia materials could significantly impact the long-term success of these newer materials. Clinicians should be aware that these cubic containing materials may perform differently long-term than the very strong traditional 3Y-TZP materials and to follow manufacturer instructions on required material thickness and indications for use to prevent premature failure of the restoration.

An Investigation of the Effect of Modifying and Reusing Impression Copings on Transfer of Implant Analog Position and Angulation.

AIM: The aim of this research was to determine whether sterilization and reutilization of impression copings had an impact on the accuracy of casts made for multiimplant restorations. MATERIALS AND METHODS: Four master casts embedded with five implant analogs were fabricated. Polyvinyl siloxane (PVS) impressions of the master cast with copings attached to the analogs were made and poured in dental stone. The impression copings were subjected to cleaning and sterilization. These processes were repeated 30 cycles for each of the two groups of five impression copings: one without modification and one with modification that included air abrasion and PVS adhesive. A coordinate measuring machine (CMM) was used to measure relative angles and distances between the reference analog and analogs. The relative angles and distances measured on the stone casts were compared to the master resin cast to obtain positional and angular displacements. RESULTS: For impression copings that were not modified, a significant difference was detected for both positional and angular displacements. For impression copings that were modified, a significant change was observed only for positional displacement. The maximum discrepancies measured for positional and angular displacements after 30 cycles of reuse were only 81 µm and 0.46°, respectively, regardless of the modification. CONCLUSION: Within the limitations of this study, unmodified impression copings that have undergone 30 cycles of cleaning and sterilization appeared to incur more impression inaccuracy than those impression copings that were modified by airborne-particle abrasion and PVS adhesive. CLINICAL SIGNIFICANCE: Impression copings used in this study can likely be recycled up to 30 times without reducing the accuracy of the impression to a level that may be considered clinically significant.

Concise Review: Wnt Signaling Pathways in Skin Development and Epidermal Stem Cells.

Mammalian skin and its appendages constitute the integumentary system forming a barrier between the organism and its environment. During development, skin epidermal cells divide rapidly and stratify into a multilayered epithelium, as well as invaginate downward in the underlying mesenchyme to form hair follicles (HFs). In postnatal skin, the interfollicular epidermal (IFE) cells continuously proliferate and differentiate while HFs undergo cycles of regeneration. Epidermal regeneration is fueled by epidermal stem cells (SCs) located in the basal layer of the IFE and the outer layer of the bulge in the HF. Epidermal development and SC behavior are mainly regulated by various extrinsic cues, among which Wnt-dependent signaling pathways play crucial roles. This review not only summarizes the current knowledge of Wnt signaling pathways in the regulation of skin development and governance of SCs during tissue homeostasis, but also discusses the potential crosstalk of Wnt signaling with other pathways involved in these processes. Stem Cells 2018;36:22-35.

Lipophagy prevents activity-dependent neurodegeneration due to dihydroceramide accumulation in vivo.

Dihydroceramide desaturases are evolutionarily conserved enzymes that convert dihydroceramide (dhCer) to ceramide (Cer). While elevated Cer levels cause neurodegenerative diseases, the neuronal activity of its direct precursor, dhCer, remains unclear. We show that knockout of the fly dhCer desaturase gene, infertile crescent (ifc), results in larval lethality with increased dhCer and decreased Cer levels. Light stimulation leads to ROS increase and apoptotic cell death in ifc-KO photoreceptors, resulting in activity-dependent neurodegeneration. Lipid-containing Atg8/LC3-positive puncta accumulate in ifc-KO photoreceptors, suggesting lipophagy activation. Further enhancing lipophagy reduces lipid droplet accumulation and rescues ifc-KO defects, indicating that lipophagy plays a protective role. Reducing dhCer synthesis prevents photoreceptor degeneration and rescues ifc-KO lethality, while supplementing downstream sphingolipids does not. These results pinpoint that dhCer accumulation is responsible for ifc-KO defects. Human dhCer desaturase rescues ifc-KO larval lethality, and rapamycin reverses defects caused by dhCer accumulation in human neuroblastoma cells, suggesting evolutionarily conserved functions. This study demonstrates a novel requirement for dhCer desaturase in neuronal maintenance in vivo and shows that lipophagy activation prevents activity-dependent degeneration caused by dhCer accumulation.

RNAi screens in mice identify physiological regulators of oncogenic growth.

Tissue growth is the multifaceted outcome of a cell's intrinsic capabilities and its interactions with the surrounding environment. Decoding these complexities is essential for understanding human development and tumorigenesis. Here we tackle this problem by carrying out the first genome-wide RNA-interference-mediated screens in mice. Focusing on skin development and oncogenic (Hras(G12V)-induced) hyperplasia, our screens uncover previously unknown as well as anticipated regulators of embryonic epidermal growth. Among the top oncogenic screen hits are Mllt6 and the Wnt effector ß-catenin, which maintain Hras(G12V)-dependent hyperproliferation. We also expose ß-catenin as an unanticipated antagonist of normal epidermal growth, functioning through Wnt-independent intercellular adhesion. Finally, we validate functional significance in mouse and human cancers, thereby establishing the feasibility of in vivo mammalian genome-wide investigations to dissect tissue development and tumorigenesis. By documenting some oncogenic growth regulators, we pave the way for future investigations of other hits and raise promise for unearthing new targets for cancer therapies.

Mis-anaesthetized society: expectancies and recreational use of ketamine in Taiwan.

BACKGROUND: The popularity of ketamine for recreational use has been increasing in Asia, including Taiwan. Still, little known about the pattern of ketamine expectancies and whether such patterns are related to ketamine use. This study aimed to examine whether the positive and negative ketamine expectancies are differentially associated with ketamine-using behavior, and whether such relationship may differ by early-onset use of tobacco or alcohol. METHODS: Participants were recruited using respondent-driven sampling (RDS) among regular tobacco and alcohol users, aged 18 to 50, residing in Taipei from 2007 to 2010. Totally 1115 participants (with an age distribution skewed to the right, median = 26; interquartile range: 22-32) had information on substance use and completed a 12-item ketamine expectancies questionnaire (with 6 positive and 6 negative statements). Using two axes of High and Low expectancies, the four combinations of binary positive and binary negative ketamine expectancies were created. Each participant's drug-using experience was categorized into illicit drug naïve, exclusive ketamine use, polydrug ketamine use, or other illicit drug use. Using the weights in the network output by RDS Analysis Tool, multivariable logistic regression analysis was then conducted. RESULTS: The weighted prevalence was 2.4% for exclusive ketamine use, 9.0% for polydrug ketamine use, and 9.1% for the other illicit drug use. Ketamine users (11.4%) had greater positive expectancies and lower negative expectancies, particularly the combination of High Positive with Low Negative, as compared to the illicit drug-naïve or other illicit drug users. After adjustment for early-onset tobacco (or alcohol) use and sociodemographic characteristics, High Positive, Low Negative, and their combination of High Positive-Low Negative expectancies remained strongly associated with ketamine uses, without evidence of moderation from early-onset use of tobacco or alcohol. CONCLUSIONS: Positive and negative ketamine expectancies were associated in opposite directions with ketamine use, independent of early-onset use of tobacco or alcohol. Our results indicate ketamine expectancies as possible targets for future intervention and prevention of ketamine use, with a less confrontational feedback on decreasing an individual's positive expectancies is essential in preventing young people from the initiation of ketamine use.

EZH1 and EZH2 cogovern histone H3K27 trimethylation and are essential for hair follicle homeostasis and wound repair.

Polycomb protein group (PcG)-dependent trimethylation on H3K27 (H3K27me3) regulates identity of embryonic stem cells (ESCs). How H3K27me3 governs adult SCs and tissue development is unclear. Here, we conditionally target H3K27 methyltransferases Ezh2 and Ezh1 to address their roles in mouse skin homeostasis. Postnatal phenotypes appear only in doubly targeted skin, where H3K27me3 is abolished, revealing functional redundancy in EZH1/2 proteins. Surprisingly, while Ezh1/2-null hair follicles (HFs) arrest morphogenesis and degenerate due to defective proliferation and increased apoptosis, epidermis hyperproliferates and survives engraftment. mRNA microarray studies reveal that, despite these striking phenotypic differences, similar genes are up-regulated in HF and epidermal Ezh1/2-null progenitors. Featured prominently are (1) PcG-controlled nonskin lineage genes, whose expression is still significantly lower than in native tissues, and (2) the PcG-regulated Ink4a/Inkb/Arf locus. Interestingly, when EZH1/2 are absent, even though Ink4a/Arf/Ink4b genes are fully activated in HF cells, they are only partially so in epidermal progenitors. Importantly, transduction of Ink4b/Ink4a/Arf shRNAs restores proliferation/survival of Ezh1/2-null HF progenitors in vitro, pointing toward the relevance of this locus to the observed HF phenotypes. Our findings reveal new insights into Polycomb-dependent tissue control, and provide a new twist to how different progenitors within one tissue respond to loss of H3K27me3.

Fracture Resistance of Pressed and Milled Lithium Disilicate Anterior Complete Coverage Restorations Following Endodontic Access Preparation.

PURPOSE: This in vitro study evaluated the fracture resistance and clinical prognosis of anterior lithium disilicate crowns (e.max Press and e.max CAD), following endodontic access and repair. The research design simulates intraoral loading conditions to produce clinically applicable results. MATERIALS AND METHODS: Monolithic anterior crowns, based on #8 anatomy, were fabricated from e.max Press ingots and e.max CAD blocks and adhesively bonded on identical dies milled out of a dentin analog material (NEMA G10). Specimens were divided into 4 groups: intact pressed, repaired pressed, intact milled, and repaired milled (n = 15/group). Repaired pressed and repaired milled were prepared with a standardized endodontic access and repaired using a porcelain repair system and composite resin. All crowns were cyclically loaded under simulated oral conditions and then loaded to failure in water, using a universal testing machine. Data were interpreted using ANOVA/Tukey post-hoc test (α = 0.05). RESULTS: Mean loads to failure ranged from 758.9 to 931.4 N for the 4 groups, indicating that both fabrication techniques, pressed and milled, yielded restorations that could reasonably withstand maximum masticatory forces. The pressed groups (923.7 N) exhibited significantly higher fracture resistance than the milled groups (797.5 N), p = 0.0002. When milled and pressed groups were categorized into intact and repaired subgroups, no difference was found in fracture resistance between the subgroups. Differences were noted in the modes of fracture, where the milled groups (intact and repaired) exhibited higher frequency of catastrophic fractures than the pressed groups. CONCLUSIONS: Endodontic access preparation does not appear to affect fracture resistance of an anterior lithium disilicate restoration, suggesting that replacement may not be necessary. Fabrication technique had a significant effect on fracture resistance and fracture mode of lithium disilicate restorations. The pressed fabrication technique resulted in significantly greater crown strength and fracture resistance than the milled technique.