10-Methacryloyloxydecyl Dihydrogen Phosphate (10-MDP)-Containing Cleaner Improves Bond Strength to Contaminated Monolithic Zirconia: An In-Vitro Study

Contamination of zirconia restorations before cementation can impair the resin–zirconia bonding durability. The objective of this study was to evaluate the effect of human saliva or blood decontamination with 10-methacryloyloxydecyl dihydrogen phosphate (10-MDP)-containing cleaner on the resin–zirconia shear bond strength (SBS). Methods: A total of 220 zirconia specimens were prepared and air-abraded and randomly distributed into 11 groups (n = 20 per group). Except for the control group (no contamination), zirconia specimens were contaminated with either human saliva (five groups) or blood (five groups), and then subjected to one of five cleaning methods: water rinsing, 38% phosphoric acid etchant (Pulpdent Corp., Watertown, MA, USA), 70% isopropanol alcohol (Avalon Pharma, Riyadh, Saudi Arabia), Ivoclean (Ivoclar Vivadent, Schaan, Lichtenstein) and Katana Cleaner (Kuraray Noritake, Tokyo, Japan). The resin–zirconia SBS was tested at 24 h and after thermocycling (10 k cycles). Three-way ANOVA followed by Tukey’s multiple comparisons test were utilized to analyze the SBS data. Failure modes were evaluated using a scanning electron microscope. Results: Both blood and saliva significantly affected resin–zirconia SBS as contaminants. After thermocycling, there was no statistically significant difference between SBS obtained after decontamination with the Katana Cleaner (blood, 6.026 ± 2.805 MPa; saliva, 5.206 ± 2.212 MPa) or Ivoclean (blood, 7.08 ± 3.309 MPa; saliva, 6.297 ± 3.083 MPa), and the control group (no contamination, 7.479 ± 3.64 MPa). Adhesive and mixed failures were the most frequent among the tested groups. Conclusion: Both 10-MDP-containing cleaner (Katana Cleaner) and zirconium oxide-containing cleaner (Ivoclean) could eliminate the negative effect of saliva and blood contamination on resin–zirconia SBS.     

IOX-101 Reverses Drug Resistance Through Suppression of Akt/mTOR/NF-κB Signaling in Cancer Stem Cell-Like,Sphere-Forming NSCLC Cell

Drug discovery research to fight lung cancer is incessantly challenged by drug resistance. In this study, we used drug-resistant lung cancer stem like cells (A549-CS) to compare the efficacy of standard drugs like cisplatin (DDP) and gemcitabine (GEM) with a novel arylidene derivative IOX-101. A549-CS was derived from regular A549 cells by growing in special media. Resistance proteins were detected using Western blotting. Cell proliferations were assessed by MTT assay. Cytokine release was enumerated using enzyme-linked immunosorbent assay. The effect of drugs on apoptosis and cell cycle was studied with flow cytometry protocols. Apoptosis-related proteins, caspases, and other signaling protein expressions like Akt and mammalian target of rapamycin (mTOR) were assessed by Western blotting. Expression of CD133 and nuclear factor B (NF- B) phosphorylation was assessed using flow cytometry. A549-CS showed significant increase in CD133 expression in comparison with A549 cells. Expression of resistance markers like MDR-1, lung resistance protein (LRP), and GST-II were detected in A549-CS. While DDP and GEM had relatively lower efficacy in A549-CS, IOX-101 inhibited the proliferation of both A549 and A549-CS with GI₅₀ values of 268 and 296.5 nM, respectively. IOX-101 increased the sub-G₀ phase in the cell cycle of A549-CS and increased the percentage of apoptotic cells. Western blot analysis revealed activation of caspases, Bax, and reduction in Bcl-2 levels. Further mechanistic investigation revealed IOX-101 to deactivate Akt, mTOR, and NF- B signaling in A549-CS cells. Additionally, IOX-101 treatment to A549-CS also reversed MDR-1 and LRP expressions. Collectively, our results demonstrate efficacy of IOX-101 in A549-CS, which was resistant against the tested standard drugs. The activity was mediated by suppressing Akt/mTOR/NF- B signaling.     

Heterogeneity in hereditary pancreatitis

Hereditary pancreatitis (HP) is the most common form of chronic relapsing pancreatitis in childhood, and may account for ∼25% of adult cases with chronic idiopathic pancreatitis. Recently, an arginine-histidine (R117H) mutation within the cationic trypsinogen gene was found in 5/5 families studied with HP. In this study we report on the results of linkage and direct mutational analysis for the common R117H mutation examined in 8 nonrelated families with hereditary pancreatitis. Two-point linkage analysis with the 7q35 marker D7S676, done initially in 4 families, yielded lod scores that were positive in 2, negative in one, and weakly positive in one. Direct mutational analysis of exon 3 of the cationic trypsinogen gene in 6 families showed that all symptomatic individuals tested were heterozygous for the R117H mutation. Also, several asymptomatic but at-risk relatives were found to be heterozygous for this mutation. Affected individuals in the remaining 2 families did not have the mutation. Radiation hybrid mapping using the Genebridge 4 panel assigned the trypsinogen gene to chromosome region 7q35, 2.9 cR distal to ETS WI-9353 and 3.8 cR proximal the dinucleotide repeat marker D7S676. The negative linkage and absence of the trypsinogen mutation in 2/8 families suggest locus heterogeneity in HP. Analysis of the R117H mutation is useful in identifying presymptomatic “at-risk” relatives and in genetic counseling. Also, it can be useful in identifying children and adults with isolated chronic idiopathic pancreatitis. Am. J. Med. Genet. 77:47–53, 1998. © 1998 Wiley-Liss, Inc.     

Staged percutaneous atrial septal defect closure and pulmonic balloon valvuloplasty in an adult with congenital heart disease

Combined atrial septal defect and pulmonic stenosis, while a common occurrence in children, is relatively uncommon in adults. There is no widely accepted order in which the defects should be corrected. We report a case that highlights the hemodynamics and the technical dilemma of deciding which lesion to correct first. © 2008 Wiley‐Liss, Inc.     

An artificial molecular switch that mimics the visual pigment and completes its photocycle in picoseconds

Single molecules that act as light-energy transducers (e.g., converting the energy of a photon into atomic-level mechanical motion) are examples of minimal molecular devices. Here, we focus on a molecular switch designed by merging a conformationally locked diarylidene skeleton with a retinal-like Schiff base and capable of mimicking, in solution, different aspects of the transduction of the visual pigment Rhodopsin. Complementary ab initio multiconfigurational quantum chemistry-based computations and time-resolved spectroscopy are used to follow the light-induced isomerization of the switch in methanol. The results show that, similar to rhodopsin, the isomerization occurs on a 0.3-ps time scale and is followed by <10-ps cooling and solvation. The entire (2-photon-powered) switch cycle was traced by following the evolution of its infrared spectrum. These measurements indicate that a full cycle can be completed within 20 ps.     

Hypovitaminosis D and cardiometabolic risk factors among non-obese youth

Hypovitaminosis D and increased cardiometabolic risk have been well established in adults. This study aims to determine whether or not vitamin D also influences cardiometabolic risk in children and adolescents. To test this hypothesis, we recruited 186 boys (mean age 12.4 ± 3.7 years) and 114 girls (11.6 ± 3.7) in a cross-sectional observational study. Anthropometrics were obtained and morning fasting blood samples were collected. Serum glucose and lipid profile were determined using routine methods. Serum 25-hydroxyvitamin D was quantified using an enzyme-linked immunosorbent assay. In our population, approximately 10% of subjects had severe 25-hydroxyvitamin D deficiency (< 12.5 nmol/L), while 50% of the boys and 40% of the girls had mild vitamin D deficiency (12.5–24.9 nmol/L). Circulating 25-hydroxyvitamin D concentrations were inversely correlated with age, body mass index (BMI), blood pressure, waist and hip circumferences and serum triglyceride concentrations, and positively associated with HDL-cholesterol. Age and systolic blood pressure were significant predictors of 25-hydroxyvitamin D, explaining about 30% of the variance (p = 0.0005). In conclusion, significant associations between serum 25-hydroxyvitamin D and cardiometabolic parameters support promising cardioprotective benefits from vitamin D sufficiency at an early age. Follow-up with prospective clinical intervention studies are needed to validate this hypothesis.     

Elective intensive care after lung resection: a multicentric propensity-matched comparison of outcome

The study was aimed at assessing the influence of the elective ICU admission on the early outcome after major lung resection by analyzing the different postoperative management policies of two centers. Center A managed all patients in a dedicated ward, resorting to ICU for complications requiring invasive assisted ventilation. In center B, high-risk patients were electively transferred to ICU immediately after operation. Propensity score was used to match those patients of center B electively admitted to ICU (96 of 157), with counterparts from center A (96 of 205). The outcome of these matched pairs were then compared. There was a trend of reduced total morbidity (23% vs. 35%, respectively; P=0.06), cardiovascular (13.5% vs. 23%, respectively; P=0.09) and pulmonary complication rates (9.3% vs. 18%, respectively; P=0.09), but a longer postoperative hospital stay (11.5 vs. 9.7, respectively; P=0.015) in the patients electively admitted to ICU, compared to matched center A patients. Mortality rates were not different (7.3% vs. 7.3%; P=1). Since the elective postoperative ICU admission did not show a clear-cut outcome benefit over the management in a dedicated ward, this practice should be limited to highly selected patients in order to efficiently utilize the available resources.     

Isoniazid acetylation in a group of Tunisian patients. Report of 620 patients

Isoniazid is a first line antituberculosis drug metabolized mainly in the liver by the Nacetyltransferase. There are differences between individuals in acetylation metabolism. Subjects are thereby characterized as being rapid or slow acetylators. The purpose is to study the distribution pattern of acetylation in patients with tuberculosis followed up at the teaching Hospital of La Rabta. The determination of acetylator phenotype was carried out on 620 tuberculosis patients during a period of 12 years. There were 483 men and 137 women with a median age of 40.3 years. The test was investigated before drug regimen administration at the dose of 5 mg/kg. A blood sample was taken three hours after the first administration. The determination of acetylation profile was worked out by Vivien hypothesis. In our population 391 were low and 229 were fast acetylators. The median dose recommended within the test was 3.04 mg/kg/day. 56% of our patients were initially receiving high dose of isoniazid. An increase in serum transaminase was initially observed in 60 patients among whom 47 slow acetylators. After dose adaptation, 53 patients had improved their biological abnormalities. The majority of Tunisian population seem to belong to slow acetylators modal. The frequency of hepatotoxicity suggests reducing the recommended dose of isoniazid from 5 to 3 mg/kg/day.     

Binding of the anticancer prodrug CB1954 to the activating enzyme NQO2 revealed by the crystal structure of their complex

CB1954 is an attractive prodrug for directed-enzyme prodrug therapy (DEPT) and a conventional prodrug against tumors in which the enzyme NQO2 is highly expressed. We have determined the crystal structure of the NQO2-CB1954 complex to 2.0 A resolution. The binding of the prodrug is governed by hydrophobic forces, while two key electrostatic contacts determine the specific orientation of the ligand. The structure also reveals an unfavorable interaction, therefore suggesting possible avenues for DEPT-tailored engineering studies.