Effect of Multiple Firings on the Microshear Bond Strength Between a Translucent Zirconia and a Resin Cement.

PURPOSE: This study investigated the microshear bond strength between a resin cement and a translucent zirconia subjected to multiple characterization firings. METHODS AND MATERIALS: 5Y-PSZ zirconia blocks (Katana UTML) were sliced, sintered (1550°C, 2 h), and randomly divided into six groups (n=10) according to the number of characterization firings (0, 1, 2, 3, 5, or 10) and aging (baseline or after thermocycling). Each characterization firing was performed at 750°C for 1 minute. The ceramic surfaces were all sandblasted with 50 µm Al2O3 and silanized. Then, cylinders of resin cement (0.96 mm diameter × 2 mm height) were bonded onto their surfaces. The baseline samples were immersed in distilled water for 24 hours before the microshear bond strength (µSBS) tests. The aged samples were tested after 5000 thermocycles in water (5°C-55°C). The failure modes were classified as adhesive, predominantly adhesive, or cohesive. Scanning electron microscope images of the failure modes and the ceramic surfaces after the firings were taken. The µSBS data were analyzed by two-way ANOVA and Tukey's test. RESULTS: The number of characterization firings and aging affected the bond strength. The highest bond strength values were observed from the 2-firing group at baseline. The µSBS results after 1, 2, or 3 characterization firings were similar at baseline and after aging. On the other hand, 0, 5, and 10 firings revealed the lowest bond strengths. The most frequent failures were adhesive and predominantly adhesive. Zirconia grains were not affected by the multiple firings. CONCLUSION: One to three characterization firings after sintering improve the bond strength of 5Y-PSZ to the resin cement when compared to none or several (five or ten) firing cycles.

Quality of life in patients with oral potentially malignant disorders: oral lichen planus and oral epithelial dysplasia.

OBJECTIVE: The aim of this study was to evaluate and compare quality of life (QoL) parameters in patients with oral potential malignant disorders (OPMDs), namely, oral lichen planus (OLP) and oral epithelial dysplasia (OED). STUDY DESIGN: A cross-sectional study was completed at the oral maxillofacial surgery/oral medicine practices at University of Pennsylvania. Patients with clinical and histopathologic confirmation of OLP or OED from January to June 2021 were included in the study. The primary predictor variable was the OPMD type. The primary outcome variable was the score of 3 separate surveys: the Chronic Oral Mucosal Disease Questionnaire-26 (COMDQ-26), Oral Potential Malignant Disorder QoL Questionnaire (OPMDQoL), and Hospital Anxiety and Depression Scale. Multiple linear regression was used to determine independent predictors of increased/decreased questionnaire scores. RESULTS: The final study sample consisted of 100 patients:53 patients had OLP (53.0%), 39 patients had OED (39.0%), and 8 patients had OLP with OED (8.0%). Relative to OED, OLP added 15.7 points to the COMDQ-26 survey score (P < .001). Relative to OED, OLP added 8.9 points to the OPMDQoL survey score (P = .003). CONCLUSIONS: Oral lichen planus shows significantly poorer QoL specifically within the COMD-26 and OPMDQoL questionnaires, compared with OED. Additionally, patients with OPMDs aged 40 to 64 years were independently associated with higher COMD-26 scores compared with older patients (>65 years).

Effects of Continuous Gamma-Ray Exposure In Utero in B6C3F1 Mice on Gestation Day 18 and at 10 Weeks of Age.

Pregnant C57BL/6JJcl mice were exposed to γ rays at low dose rate (20 mGy/day, LDR) or medium dose rate (200 and 400 mGy/day, MDR) from gestation day (GD) 0-18 to total accumulated doses of 360, 3,600 and 7,200 mGy, respectively. An additional group of pregnant mice were acutely exposed to 2 Gy at high dose rate (HDR) of 0.77 Gy/min on GD 11. In experiment 1, fetuses collected via cesarean section on GD 18 were examined for external and skeletal abnormalities. While the results of LDR exposure (20 mGy/day) did not significantly differ from the nonirradiated controls in all parameters examined, MDR (200 and 400 mGy/day) and acute HDR (2 Gy) exposure caused growth retardation and significantly increased incidence of unossified bones. Increased incidence of external abnormalities was observed only in the acute HDR group. In experiment 2, the dams were allowed to give birth and the pups were clinically monitored and weighed periodically until 10 weeks of age when they were sacrificed and subjected to pathological examination. Pups exposed at MDRs of 200 and 400 mGy/dayand at acute HDR of 0.77 Gy/min had lower bodyweights from weaning (3 weeks) to 10 weeks of age except for females exposed to 400 mGy/day MDR. None of the pups exposed to an acute 2 Gy dose on GD 11 survived to 10 weeks of age. Histopathological changes were not significantly different between the nonirradiated control and the 20 mGy/day LDR groups. However, at both MDR exposures of 200 and 400 mGy/day. gonadal (testes and ovary) hypoplasia/atrophy was observed in all the 10-week-old pups. Our results show that in utero LDR exposure to 20 mGy/day for the entire gestation period did not cause any significant effect in pups when compared to the nonirradiated controls up to 10 weeks of age. However, pups exposed in utero to MDRs showed dose-related growth retardation with delayed ossifications (400 mGy/day) and gonadal hypoplasia/atrophy. These findings suggest that increased post-implantation loss in dams exposed at MDR is due to early embryonic deaths resulting in early resorption.

Manifestation of hopping conductivity and granularity within phase diagrams of LaO1-x F x BiS2, Sr1-x La x FBiS2 and related BiS2-based compounds.

Layered BiS [Formula: see text] -based series, such as LaO [Formula: see text] F [Formula: see text] BiS [Formula: see text] and Sr [Formula: see text] La [Formula: see text] FBiS [Formula: see text] , offer ideal examples for studying normal and superconducting phase diagram of a solid solution that evolves from a nonmagnetic band-insulator parent. We constructed typical [Formula: see text] phase diagrams of these systems based on events occurring in thermal evolution of their electrical resistivity, [Formula: see text]. Overall evolution of these diagrams can be rationalized in terms of (i) Mott-Efros-Shklovskii scenario which, within the semiconducting [Formula: see text] regime ([Formula: see text] metal-insulator transition), describes the doping influence on the thermally activated hopping conductivity. (ii) A granular metal (superconductor) scenario which, within [Formula: see text], describes the evolution of normal and superconducting properties in terms of conductance g, Coulomb charging energy E c and Josephson coupling J; their joint influence is usually captured within a [Formula: see text] phase diagram. Based on analysis of the granular character of [Formula: see text], we converted the [Formula: see text] diagrams into projected g - T diagrams which, being fundamental, allow a better understanding of evolution of various granular-related properties (in particular the hallmarks of normal-state [Formula: see text] feature and superconductor-insulator transition) and how such properties are influenced by x, pressure or heat treatment.

Pathology of Serially Sacrificed Female B6C3F1 Mice Continuously Exposed to Very Low-Dose-Rate Gamma Rays.

We have previously reported on life span shortening as well as increased incidence rates in several neoplasms in B6C3F1 mice that were continuously exposed to 21 mGy/day of gamma rays for 400 days. To clarify whether the life shortening was due to early appearance of neoplasms (shortened latency) or increased promotion/progression, 8-week-old female specific-pathogen-free B6C3F1 mice were gamma-ray irradiated at a low dose rate of 20 mGy/day for 400 days. At 100 days postirradiation, 60-90 mice were sacrificed, and thereafter every 100 days alongside the age-matched nonirradiated controls, for 700 days. Additional groups were allowed to live out their natural life span. Pathological examination was performed on all mice to identify lesions, non-neoplastic and neoplastic, as well as to determine the cause of death. Body weights were significantly increased in irradiated mice from sacrifice days 200-500. Incidence rates for spontaneously occurring non-neoplastic lesions, such as adrenal subcapsular cell hyperplasia, fatty degeneration of the liver, atrophy and tubulostromal hyperplasia of the ovaries, were significantly increased in irradiated mice. Significantly increased incidence rates with no shortening of latency periods were observed in irradiated mice for malignant lymphomas, hepatocellular adenomas/carcinomas, bronchioloalveolar adenomas, harderian gland adenoma/adenocarcinoma. Shortened latencies with significantly increased incidence rates were observed for adrenal subcapsular cell adenomas and ovarian neoplasms (tubulostromal adenoma, granulosa cell tumors) in irradiated mice. Life span shortening in mice exposed to 20 mGy/day was mostly due to malignant lymphomas. Multiple primary neoplasms were significantly increased in mice exposed to 20 mGy/day from sacrifice days 400-700 and in the life span group. Our results confirm that continuous low-dose-rate gamma-ray irradiation of female B6C3F1 mice causes both cancer induction (shortened latency) and promotion/progression (early death), depending on the neoplasm's organ/tissue of origin.

LIM-domain protein AJUBA suppresses malignant mesothelioma cell proliferation via Hippo signaling cascade.

Malignant mesothelioma (MM) is one of the most aggressive neoplasms usually associated with asbestos exposure and is highly refractory to current therapeutic modalities. MMs show frequent activation of a transcriptional coactivator Yes-associated protein (YAP), which is attributed to the neurofibromatosis type 2 (NF2)-Hippo pathway dysfunction, leading to deregulated cell proliferation and acquisition of a malignant phenotype. However, the whole mechanism of disordered YAP activation in MMs has not yet been well clarified. In the present study, we investigated various components of the NF2-Hippo pathway, and eventually found that MM cells frequently showed downregulation of LIM-domain protein AJUBA, a binding partner of large tumor suppressor type 2 (LATS2), which is one of the last-step kinases of the NF2-Hippo pathway. Although loss of AJUBA expression was independent of the alteration status of other Hippo pathway components, MM cell lines with AJUBA inactivation showed a more dephosphorylated (activated) level of YAP. Immunohistochemical analysis showed frequent downregulation of AJUBA in primary MMs, which was associated with YAP constitutive activation. We found that AJUBA transduction into MM cells significantly suppressed promoter activities of YAP-target genes, and the suppression of YAP activity by AJUBA was remarkably canceled by knockdown of LATS2. In connection with these results, transduction of AJUBA-expressing lentivirus significantly inhibited the proliferation and anchorage-independent growth of the MM cells that harbored ordinary LATS family expression. Taken together, our findings indicate that AJUBA negatively regulates YAP activity through the LATS family, and inactivation of AJUBA is a novel key mechanism in MM cell proliferation.

The Be K-edge in beryllium oxide and chalcogenides: soft x-ray absorption spectra from first-principles theory and experiment.

We have carried out a theoretical and experimental investigation of the beryllium K-edge soft x-ray absorption fine structure of beryllium compounds in the oxygen group, considering BeO, BeS, BeSe, and BeTe. Theoretical spectra are obtained ab initio, through many-body perturbation theory, by solving the Bethe-Salpeter equation (BSE), and by supercell calculations using the core-hole approximation. All calculations are performed with the full-potential linearized augmented plane-wave method. It is found that the two different theoretical approaches produce a similar fine structure, in good agreement with the experimental data. Using the BSE results, we interpret the spectra, distinguishing between bound core-excitons and higher energy excitations.

A Phase II clinical trial of a mixture of plasma-derived factor VIIa and factor X (MC710) in haemophilia patients with inhibitors: haemostatic efficacy, safety and pharmacokinetics/pharmacodynamics.

MC710, a mixture of plasma-derived activated factor VII and factor X at a protein weight ratio of 1:10, is a novel bypassing agent for haemostasis in haemophilia patients with inhibitors. In a Phase II trial, we evaluated the haemostatic efficacy and safety of single doses of MC710, and investigated pharmacokinetic and pharmacodynamic parameters in nine joint bleeding episodes in six male haemophilia patients with inhibitors. This trial was a multi-centre, open-label, non-randomized study of two doses (60 and 120 µg kg(-1) as FVIIa dose), allowing the re-administration of different MC710 dosages to the same subjects. Haemostatic efficacy was assessed by evaluating reduction in pain and swelling, as well as increase in range of motion in a bleeding joint. The results of the study showed that in nine bleeding episodes, seven treatments were rated as 'excellent' or 'effective' according to investigator's rating system of efficacy at 8 h after administration. No serious or severe adverse events were observed after administration; furthermore, measurement of several diagnostic markers revealed no signs or symptoms of disseminated intravascular coagulation (DIC). The haemostatic potential of MC710 was confirmed at doses of 60 and 120 µg kg(-1) in this trial. MC710 is thus expected to be a safe and efficacious novel bypassing agent for controlling bleeding in haemophilia patients with inhibitors.

Improved delineation of arteries in the posterior fossa of the brain by model-based iterative reconstruction in volume-rendered 3D CT angiography.

BACKGROUND AND PURPOSE: Improved CTA delineation of arteries and unruptured aneurysms is clinically desired in the posterior fossa. We present a novel model-based iterative reconstruction that models system statistics and optics to improve CT image quality. We investigated the utility of MBIR for improving delineation of arteries in the posterior fossa on 3D brain CTA. MATERIALS AND METHODS: Using filtered back-projection with a standard kernel and MBIR, we reconstructed axial images of 0.625-mm thickness of 28 consecutive patients (14 men; mean age, 58.6 ± 14.6 years) who underwent 64-detector brain CTA. We placed regions of interest on the axial images, measured the mean CT value in the basilar artery and the value and SD in the pons and bilateral cerebellar hemispheres, and calculated the contrast-to-noise ratio of the brain arteries in the posterior fossa. Using volume-rendered CTA and a 4-point scale, 2 radiologists independently graded delineation of the BA, bilateral vertebral artery, superior cerebellar artery, and anterior and posterior inferior cerebellar arteries. We compared the results between FBP and MBIR by using paired t and Wilcoxon signed-rank tests. RESULTS: Compared with FBP, MBIR significantly improved the contrast-to-noise ratio (P < .0001) and subjective delineation of all arteries in the posterior fossa except the BA (VA, SCA, AICA, and PICA; P < .05 for all). The mean visual score by MBIR was 3.0 or higher for all those arteries except the AICA assessed by reader 1 (2.6 ± 0.7). CONCLUSIONS: With 3D brain CTA, contrast-to-noise ratio and arterial delineation of the VA, SCA, AICA, and PICA in the posterior fossa are better with MBIR than FBP.

YAP induces malignant mesothelioma cell proliferation by upregulating transcription of cell cycle-promoting genes.

Malignant mesothelioma (MM) shows frequent inactivation of the neurofibromatosis type 2 (NF2) -tumor-suppressor gene. Recent studies have documented that the Hippo signaling pathway, a downstream cascade of Merlin (a product of NF2), has a key role in organ size control and carcinogenesis by regulating cell proliferation and apoptosis. We previously reported that MMs show overexpression of Yes-associated protein (YAP) transcriptional coactivator, the main downstream effector of the Hippo signaling pathway, which results from the inactivation of NF2, LATS2 and/or SAV1 genes (the latter two encoding core components of the mammalian Hippo pathway) or amplification of YAP itself. However, the detailed roles of YAP remain unclear, especially the target genes of YAP that enhance MM cell growth and survival. Here, we demonstrated that YAP-knockdown inhibited cell motility, invasion and anchorage-independent growth as well as cell proliferation of MM cells in vitro. We analyzed genes commonly regulated by YAP in three MM cell lines with constitutive YAP-activation, and found that the major subsets of YAP-upregulating genes encode cell cycle regulators. Among them, YAP directly induced the transcription of CCND1 and FOXM1, in cooperation with TEAD transcription factor. We also found that knockdown of CCND1 and FOXM1 suppressed MM cell proliferation, although the inhibitory effects were less evident than those of YAP knockdown. These results indicate that constitutive YAP activation in MM cells promotes cell cycle progression giving more aggressive phenotypes to MM cells.

Fouling potentials of polysaccharides in membrane bioreactors (MBRs) assessed by lectin affinity chromatography.

In this study, the fouling potentials of polysaccharides contained in mixed liquor suspension in a membrane bioreactor (MBR) treating municipal wastewater were investigated using lectin affinity chromatography. This investigation was carried out with different membranes to assess the effects of membrane materials on fouling potentials of polysaccharides. In lectin affinity chromatography, some polysaccharides with high affinity to the lectin in the column can be retained in the column. The fouling potentials of the retained polysaccharides were evaluated by dead-end filtration test. Degree of reduction in fouling potential differed considerably when different lectins were used in affinity chromatography indicating that fouling potentials of polysaccharide differed depending on types of polysaccharide. Trends in the reduction of fouling potential were different depending on membrane materials. Characteristics of the organic matter associated with polysaccharides removed by lectins were investigated by means of excitation-emission matrices (EEM). The results of EEM analysis indicate that the characteristics of the organic matter eluted from different lectins were different as long as elution reagents for the lectin were different. Characteristics of the organic matter eluted from the lectins which have the same elution reagent were similar in terms of shapes of EEM fluorescence spectra. However, the trends in reduction of fouling potentials could not be explained by the characteristics of organic matter assessed by EEM analysis. On the basis of the results obtained in this study, it can be concluded that characteristics of membrane and structures or properties of sugar chain would play an important role in determining fouling potentials.

Adiposity in female B6C3F1 mice continuously irradiated with low-dose-rate gamma rays.

Abstract We previously reported significant increases in body weight in B6C3F1 mice continuously exposed to low-dose-rate (21 mGy/day) gamma rays compared to that of nonirradiated control mice (Tanaka et al., Radiat. Res. 167, 417-437, 2007). To further study the underlying cause of the increase in body weight, feed consumption, adipose tissue weight, liver and serum lipid contents, and selected factors related to glucose and lipid metabolism such as serum levels of insulin and adipocytokines were examined in female B6C3F1 mice irradiated continuously with gamma rays at 20 mGy/day in group-housed or individually housed rearing conditions. Increased body weight, adipose tissue weight, serum levels of leptin, and lipid contents of the liver and serum were observed in both group-housed (accumulated dose = 6 Gy, 43 weeks from start of irradiation) and individually housed (accumulated dose = 4.4 Gy, 31 weeks from start of irradiation) irradiated mice compared to nonirradiated controls. Feed consumption measurements, however, revealed no significant difference between irradiated mice and nonirradiated controls when mice were housed individually. Our results show for the first time that the increase in the body weight of mice continuously irradiated with low-dose-rate gamma rays is due to adiposity with no corresponding increase in feed consumption.

Pourbaix diagrams of alkaline earth metal elements by combination of first principles calculations and thermochemical data.

Based on first principles calculations for crystals and experimental thermochemical data for aqueous solutions and molecules, Pourbaix diagrams of alkaline earth metal systems at 298.15 K are constructed. Phonon frequencies are computed for all crystals of interests by the first principles method. Then individual contributions of zero-point energies and vibrational free energies are examined. The contribution of the zero-point energy is found to be 7-8% of the total formation free energy at 298.15 K in hydroxides, which can be ascribed to the presence of high frequency OH stretching modes. The agreements between computed and experimental Pourbaix diagrams are quite satisfactory.

Discovery of a potent, metabolically stabilized resorcylic lactone as an anti-inflammatory lead.

With bioactivity-guided phenotype screenings, a potent anti-inflammatory compound f152A1 has been isolated, characterized and identified as the known natural product LL-Z1640-2. Metabolic instability precluded its use for the study on animal disease models. Via total synthesis, a potent, metabolically stabilized analog ER-803064 has been created; addition of the (S)-Me group at C4 onto f152A1 has resulted in a dramatic improvement on its metabolic stability, while preserving the anti-inflammatory activities.

Near-edge structures from first principles all-electron Bethe-Salpeter equation calculations.

We obtain x-ray absorption near-edge structures (XANES) by solving the equation of motion for the two-particle Green's function for the electron-hole pair, the Bethe-Salpeter equation (BSE), within the all-electron full-potential linearized augmented plane wave method (FPLAPW). The excited states are calculated for the Li K-edge in the insulating solids LiF, Li(2)O and Li(2)S, and absorption spectra are compared with independent particle results using the random phase approximation (RPA), as well as supercell calculations using the core-hole approximation within density functional theory (DFT). The binding energies of strongly bound excitations are determined in the materials, and core-exciton wavefunctions are demonstrated for LiF.

Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal-regulated kinase activation and renal fibrosis.

Systemic administration of the potent vasodilating peptide adrenomedullin reduces cardiac and renal fibrosis in hypertensive animals. Here, we investigated the effects of kidney-specific adrenomedullin gene delivery in normotensive rats after unilateral ureteral obstruction, an established model of renal tubulointerstitial fibrosis. Overexpression of exogenous adrenomedullin in the renal interstitium following ureteral obstruction significantly prevented fibrosis and proliferation of tubular and interstitial cells. In this model, there is upregulation of connective tissue growth factor (CTGF) mRNA expression and extracellular signal-regulated kinase (ERK) phosphorylation, and adrenomedullin overexpression suppressed both of these activities without altering the blood pressure. In NRK-49F renal fibroblasts, adrenomedullin reduced transforming growth factor-beta-induced CTGF and fibronectin mRNA upregulation through the cyclic AMP/protein kinase A signaling pathway, and suppressed ERK phosphorylation and cell proliferation. In the kidneys with an obstructed ureter, adrenomedullin receptor gene expression was upregulated along with cyclic AMP production in kidney slices. The latter effect was partially blocked by a neutralizing antibody to adrenomedullin, indicating that an endogenous peptide-receptor system was activated. Our results show that overexpression of exogenous adrenomedullin in the ureteral-obstructed kidney prevents tubulointerstitial fibrosis and cell proliferation through the cyclic AMP-mediated decrease of CTGF induction and ERK phosphorylation.

Casein hydrolysate formula-induced liver dysfunction in a neonate with non-immunoglobulin E-mediated cow's milk allergy.

A 10-day-old male neonate was admitted with bilious vomiting and gross hematochezia. Peripheral eosinophilia, delayed positive skin prick test to artificial milk, and elevated eosinophil cationic protein levels suggested cow's milk allergy. Fluid infusion with prohibition of oral intake improved the digestive symptoms. Breast-feeding was resumed on hospital day 3 and only casein hydrolysate formula was fed from day 7 onward. Nevertheless, eosinophilia and elevated transaminase levels developed on day 14. Liver dysfunction associated with casein hydrolysate formula was suspected and the infant was transferred to soy formula. Eosinophil counts decreased and transaminase levels were normalized on day 19. A cow's milk protein-specific lymphocyte proliferation test was positive for alpha-casein, beta-lactoglobulin, and bovine serum albumin, indicating sensitization of T cells to cow's milk proteins. These observations suggest that careful attention should be paid to liver dysfunction in non-immunoglobulin E-mediated cow's milk allergy, even when hypoallergenic formula is used.