How drug onset rate and duration of action affect drug forgiveness.

Medication nonadherence is one of the largest problems in healthcare today, particularly for patients undergoing long-term pharmacotherapy. To combat nonadherence, it is often recommended to prescribe so-called "forgiving" drugs, which maintain their effect despite lapses in patient adherence. Nevertheless, drug forgiveness is difficult to quantify and compare between different drugs. In this paper, we construct and analyze a stochastic pharmacokinetic/pharmacodynamic (PK/PD) model to quantify and understand drug forgiveness. The model parameterizes a medication merely by an effective rate of onset of effect when the medication is taken (on-rate) and an effective rate of loss of effect when a dose is missed (off-rate). Patient dosing is modeled by a stochastic process that allows for correlations in missed doses. We analyze this "on/off" model and derive explicit formulas that show how treatment efficacy depends on drug parameters and patient adherence. As a case study, we compare the effects of nonadherence on the efficacy of various antihypertensive medications. Our analysis shows how different drugs can have identical efficacies under perfect adherence, but vastly different efficacies for adherence patterns typical of actual patients. We further demonstrate that complex PK/PD models can indeed be parameterized in terms of effective on-rates and off-rates. Finally, we have created an online app to allow pharmacometricians to explore the implications of our model and analysis.

Effect of print orientation, storage conditions, and storage time on intaglio surface accuracy of implant surgical guides fabricated by using a stereolithography technology.

STATEMENT OF PROBLEM: The accuracy of printed implant surgical guides can be affected by different factors that negatively impact the planned implant position. How print orientation, storage time, and conditions influence manufacturing accuracy remains uncertain. PURPOSE: The purpose of this in vitro study was to evaluate the influence of print orientation, storage conditions, and storage time on the intaglio surface accuracy of implant surgical guides manufactured by using a stereolithography (SLA) printer. MATERIAL AND METHODS: A tooth-supported maxillary implant surgical guide design (control file) was used to fabricate the specimens (N=40, n=10). Four groups were created based on the print orientation used: 0 (Group 0), 45 (Group 45), 70 (Group 70), and 90 degrees (Group 90). The specimens were fabricated using an SLA printer (Form 3B+) and a biocompatible dental resin (Surgical Guide Resin V1) following the manufacturer's recommended protocol. Each group was divided into 2 subgroups based on the storage conditions: light (L subgroup) and dark (D subgroup) settings. Each specimen was digitized by using a desktop scanner (Medit T710) at days 0, 1, 7, and 14. The control file and each digitized specimen were superimposed by using the best-fit technique with a metrology program (Geomagic Control X). The root mean square (RMS) error was used to calculate the discrepancies between the control files and specimen files. Three-way ANOVA and pairwise comparison Tukey tests were used to analyze trueness. The Levene test was used to assess precision (α=.05). RESULTS: Significant trueness discrepancies were found among the groups tested (P<.001), but no significant differences were found among the subgroups (P=.100) and the storage times analyzed (P=.609). Additionally, the Tukey test showed significant RMS error mean value discrepancies between Group 0 and Group 45 (P<.001), Group 0 and Group 90 (P<.001), Group 45 and Group 70 (P<.001), and Group 70 and Group 90 (P<.001). The Levene test revealed significant SD discrepancies among the groups tested (P<.05). CONCLUSIONS: The trueness and precision of the intaglio surface of the implant surgical guides manufactured by using the printer and material tested were affected by the print orientation. However, storage conditions over a 14-day period did not impact the intaglio accuracy of the specimens.

Evaluating the impact of a cemetery on groundwater by multivariate analysis.

Water analyses in conjunction with hydrological and geotechnical investigations were carried out to assess the potential for groundwater contamination from the decomposition of buried human bodies. Water samples were collected from 2007 to 2018 in three monitoring wells built within the cemetery area. Water quality was evaluated based on the determination of 25 analytical parameters (20 physical-chemical and 5 microbiological). Laboratory data reported by the local sewage water company for water collected in household cisterns located outside the cemetery area were also evaluated. Multivariate analysis showed a similar pattern between iron content, turbidity, and rainfall data collected at the rainfall station closest to the study area. This behavior is a direct consequence of soil leaching (oxisol). The physical characterization of the soil of the unsaturated area above the aquifer indicates that the absorption of body waste by the soil is favored, preventing surface contaminants from reaching the aquifer. This work also found that the water samples collected outside the cemetery area do not comply with the Brazilian limits for drinking water. In conclusion, water samples collected from monitoring wells located within the cemetery area have little to none impact on both subsurface and underground contamination.

Specificity and Reactivity of Mycobacterium tuberculosis Serine/Threonine Kinases PknG and PknB.

Mycobacterium tuberculosis (Mtb), the causative agent of Tuberculosis, has 11 eukaryotic-like serine/threonine protein kinases, which play essential roles in cell growth, signal transduction, and pathogenesis. Protein kinase G (PknG) regulates the carbon and nitrogen metabolism by phosphorylation of the glycogen accumulation regulator (GarA) protein at Thr21. Protein kinase B (PknB) is involved in cell wall synthesis and cell shape, as well as phosphorylates GarA but at Thr22. While PknG seems to be constitutively activated and recognition of GarA requires phosphorylation in its unstructured tail, PknB activation is triggered by phosphorylation of its activation loop, which allows binding of the forkhead-associated domain of GarA. In the present work, we used molecular dynamics and quantum-mechanics/molecular mechanics simulations of the catalytically competent complex and kinase activity assays to understand PknG/PknB specificity and reactivity toward GarA. Two hydrophobic residues in GarA, Val24 and Phe25, seem essential for PknG binding and allow specificity for Thr21 phosphorylation. On the other hand, phosphorylated residues in PknB bind Arg26 in GarA and regulate its specificity for Thr22. We also provide a detailed analysis of the free energy profile for the phospho-transfer reaction and show why PknG has a constitutively active conformation not requiring priming phosphorylation in contrast to PknB. Our results provide new insights into these two key enzymes relevant for Mtb and the mechanisms of serine/threonine phosphorylation in bacteria.

Should patients skip late doses of medication? A pharmacokinetic perspective.

Missed doses, late doses, and other dosing irregularities are major barriers to effective pharmacotherapy, especially for the treatment of chronic conditions. What should a patient do if they did not take their last dose at the prescribed time? Should they take it late or skip it? In this paper, we investigate the pharmacokinetic effects of taking a late dose. We consider a single compartment model with linear absorption and elimination for a patient instructed to take doses at regular time intervals. We suppose that the patient forgets to take a dose and then realizes some time later and must decide what remedial steps to take. Using mathematical analysis, we derive several metrics which quantify the effects of taking the dose late. The metrics involve the difference between the drug concentration time courses for the case that the dose is taken late and the case that the dose is taken on time. In particular, the metrics are the integral of the absolute difference over all time, the maximum of the difference, and the maximum of the integral of the difference over any single dosing interval. We apply these general mathematical formulas to levothyroxine, atorvastatin, and immediate release and extended release formulations of lamotrigine. We further show how population variability can be immediately incorporated into these results. Finally, we use this analysis to propose general principles and strategies for dealing with dosing irregularities.

Candida glabrata - basic characteristics, virulence, treatment, and resistance.

Fungal infections are currently a serious health concern. Life-threatening conditions that occur mainly in immunocompromised patients are largely caused by representatives of the genus Candida. The most common causative agent is the yeast Candida albicans, but in recent years there has been a significant shift towards Candida glabrata and other so-called non-albicans Candida yeasts (e.g. Candida tropicalis or Candida parapsilosis). Invasive infections caused by the multidrug-resistant yeast Candida auris are associated with high mortality. There are several differences between C. glabrata and other causative agents of candidiasis in biological characteristics and virulence factors. The innate increased resistance to azoles along with the ability to rapidly acquire resistance to other groups of antifungal agents is a dangerous combination which makes it difficult to manage Candida infections. A better understanding of the virulence factors and mechanisms of resistance to antifungal agents can benefit the management of Candida infections. Equally important is the search for new target sites for antifungal therapy. The present work briefly summarizes the existing knowledge in this area.

Occlusal features of 5-year-old Greek children: a cross-sectional national study.

BACKGROUND: Occlusal characteristics of the primary dentition are crucial in predicting and determining permanent tooth alignment and occlusion. The aim of our study was to determine the occlusal characteristics of the primary dentition of 5-year-old children in Greece through a national pathfinder survey. METHODS: A stratified cluster sample of 1222 5-year-old children was selected according to the WHO guidelines for national pathfinder surveys. Five occlusal traits were registered clinically in centric occlusion, separately for the left and right sides: sagittal relationships of the second primary molars and primary canines, overjet, overbite, crossbite, and maxillary and mandibular spacing. RESULTS: Most children showed a flush terminal plane of primary second molars (44.8%), a class I primary canine relationship (52.2%) and normal overjet (46.4%), but a high prevalence of Class II canine relationship (25.6%) and overjet (37.8%) were also observed. A normal overbite was found in 40% of the children and 40% had a deep overbite. Spacing was apparent in both maxilla (71.1% of children) and mandible (56.4%). The prevalence of open bite and distal step molar relationship significantly rose in children with non-nutritive sucking habits. CONCLUSIONS: Νon-nutritive habits were associated to altered occlusal features. No sex significant differences were found in either the sagittal relationships of second primary molars and primary canines, or overjet, overbite, crossbite and spacing.

Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety-related behavior of adult rats.

Exposure to early life stress leads to long-term neurochemical and behavioral alterations. Stress-induced psychiatric disorders, such as depression, have recently been linked to dysregulation of glutamate signaling, mainly via its postsynaptic receptors. The role of metabotropic glutamate receptor 5 (mGluR5) in stress-induced psychopathology has been the target of several studies in humans. In rodents, blockade of mGluR5 produces antidepressant-like actions, whereas mice lacking mGluR5 exhibit altered anxiety-like behaviors and learning. In this study, we used well-known rodent models of early life stress based on mother-infant separation during the first 3 weeks of life in order to examine the effects of neonatal maternal separation on mGluR5 expression and on anxiety-related behavior in adulthood. We observed that brief (15 min) neonatal maternal separation, but not prolonged (3 h), induced increases in mGluR5 mRNA and protein expression levels in medial prefrontal cortex and mGluR5 protein levels in dorsal, but not ventral, hippocampus of adult rat brain. Behavioral testing using the open-field and the elevated-plus maze tasks showed that brief maternal separations resulted in increased exploratory and decreased anxiety-related behavior, whereas prolonged maternal separations resulted in increased anxiety-related behavior in adulthood. The data indicate that the long-lasting effects of neonatal mother-offspring separation on anxiety-like behavior and mGluR5 expression depend on the duration of maternal separation and suggest that the increased mGluR5 receptors in medial prefrontal cortex and hippocampus of adult rats exposed to brief neonatal maternal separations may underlie their heightened ability to cope with stress.

Factors influencing milk osteopontin concentration based on measurements from Danish Holstein cows.

Our objective was to determine the content of the bioactive protein osteopontin (OPN) in bovine milk and identify factors influencing its concentration. OPN is expressed in many tissues and body fluids, with by far the highest concentrations in milk. OPN plays a role in immunological and developmental processes and it has been associated with several milk production traits and lactation persistency in cows. In the present study, we report the development of an enzyme linked immunosorbent assay (ELISA) for measurement of OPN in bovine milk. The method was used to determine the concentration of OPN in milk from 661 individual Danish Holstein cows. The median OPN level was determined to 21.9 mg/l with a pronounced level of individual variation ranging from 0.4 mg/l to 67.8 mg/l. Breeding for increased OPN in cow's milk is of significant interest, however, the heritability of OPN in milk was found to be relatively low, with an estimated value of 0.19 in the current dataset. The variation explained by the herd was also found to be low suggesting that OPN levels are not affected by farm management or feeding. Interestingly, the concentration of OPN was found to increase with days in milk and to decrease with parity.

Causes, outcomes, and owner satisfaction of dogs undergoing enucleation with orbital implant placement.

OBJECTIVE: To describe clinical and histopathologic pre-operative diagnoses as well as associated post-operative complications following orbital silicone implantation in dogs undergoing enucleation and evaluate owner satisfaction. ANIMALS STUDIED: One hundred and eighty-six dogs who underwent enucleation with orbital implant. PROCEDURES: Medical records from dogs that underwent enucleation with orbital implant performed at Virginia-Maryland Veterinary Teaching Hospital between 2007 and 2019 were reviewed. Owners were surveyed via telephone regarding client satisfaction. RESULTS: Enucleation followed by orbital implant placement occurred in 215 eyes of 186 dogs. The most common pre-operative diagnoses were glaucoma (68.8%), uveitis (17.7%), cataracts (15.8%), intraocular neoplasia (13.0%), and lens luxation (10.7%). The most common histopathologic diagnoses were retinal degeneration (46.5%), uveitis (39.5%), cataract (29.8%), retinal detachment (27.4%), and secondary glaucoma (26.5%). Fourteen eyes (6.5%) from ten dogs had post-operative complications reported including orbit cellulitis (n = 11), implant migration (n = 1), and implant extrusion (n = 1). Five of these dogs (50%) had concurrent diabetes mellitus. Median complication time from surgery was 41 days (range: 11-541 days). Ninety-five owner survey responses were completed with a median time of 6.3 years following surgery. Most owners, 85.3% (n = 81), were satisfied with the post-operative outcome. CONCLUSION: Enucleation with implantation of an orbital implant is a viable and safe method for irreversibly blind eyes. Diabetes mellitus may be a risk factor for the development of post-operative complications. Intraocular neoplasia was not associated with development of post-operative complications. Results of this study indicated high owner satisfaction rates for improving cosmetic appearance after enucleation in dogs.

AutoDock Bias: improving binding mode prediction and virtual screening using known protein-ligand interactions.

SUMMARY: The performance of docking calculations can be improved by tuning parameters for the system of interest, e.g. biasing the results towards the formation of relevant protein-ligand interactions, such as known ligand pharmacophore or interaction sites derived from cosolvent molecular dynamics. AutoDock Bias is a straightforward and easy to use script-based method that allows the introduction of different types of user-defined biases for fine-tuning AutoDock4 docking calculations. AVAILABILITY AND IMPLEMENTATION: AutoDock Bias is distributed with MGLTools (since version 1.5.7), and freely available on the web at http://ccsb.scripps.edu/mgltools/ or http://autodockbias.wordpress.com. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Kinase Activation by Small Conformational Changes.

Protein kinases (PKs) are allosteric enzymes that play an essential role in signal transduction by regulating a variety of key cellular processes. Most PKs suffer conformational rearrangements upon phosphorylation that strongly enhance the catalytic activity. Generally, it involves the movement of the phosphorylated loop toward the active site and the rotation of the whole C-terminal lobe. However, not all kinases undergo such a large configurational change: The MAPK extracellular signal-regulated protein kinases ERK1 and ERK2 achieve a 50 000 fold increase in kinase activity with only a small motion of the C-terminal region. In the present work, we used a combination of molecular simulation tools to characterize the conformational landscape of ERK2 in the active (phosphorylated) and inactive (unphosphorylated) states in solution in agreement with NMR experiments. We show that the chemical reaction barrier is strongly dependent on ATP conformation and that the "active" low-barrier configuration is subtly regulated by phosphorylation, which stabilizes a key salt bridge between the conserved Lys52 and Glu69 belonging to helix-C and promotes binding of a second Mg ion. Our study highlights that the on-off switch embedded in the kinase fold can be regulated by small, medium, and large conformational changes.

Flexural strength of denture base acrylic resins processed by conventional and CAD-CAM methods.

STATEMENT OF PROBLEM: High flexural strength is one of the desirable properties for denture base resins, yet only few studies have evaluated the physical properties of newer denture bases such as computer-aided design and computer aided manufacturing (CAD-CAM) milled products. PURPOSE: The purpose of this in vitro study was to compare the flexural strength of 3 different types of denture base resins: compression molded, injection molded, and CAD-CAM milled. MATERIAL AND METHODS: Three groups (n=10) of acrylic denture base resins were tested: injection molded, compression molded, and CAD-CAM milled resin. ISO-compliant, rectangular specimens were fabricated (64×10×3.3 mm) (n=30). Specimens were stored in water for 1 week, and flexural strength was measured by using a 3-point bend test until failure. The Student t test was used to evaluate differences in the flexural strength and modulus of elasticity among specimen groups. The Bonferroni formula was used to set significance at α=.017 to account for multiple comparisons among the 3 groups. RESULTS: The flexural strength of the CAD-CAM milled group was significantly higher than that of the other 2 groups (P<.001), while the strength of the compression molded group was significantly greater than that of the injection molded group (P<.001). The flexural modulus of the CAD-CAM group was significantly higher than that of the other 2 groups (P<.001). CONCLUSIONS: CAD-CAM milled denture bases may be a useful alternative to conventionally processed denture bases in situations where increased resistance to flexural strength is needed.

The effect of diet and radiation on the bacterial symbiome of the melon fly, Zeugodacus cucurbitae (Coquillett).

BACKGROUND: Symbiotic bacteria contribute to a multitude of important biological functions such as nutrition and reproduction and affect multiple physiological factors like fitness and longevity in their insect hosts. The melon fly, Zeugodacus cucurbitae (Coquillett), is an important agricultural pest that affects a variety of cultivated plants belonging mostly to the Cucurbitaceae family. It is considered invasive and widespread in many parts of the world. Several approaches are currently being considered for the management of its populations including the environmentally friendly and effective sterile insect technique (SIT), as a component of an integrated pest management (IPM) strategy. In the present study, we examined the effect of diet and radiation on the bacterial symbiome of Z. cucurbitae flies with the use of Next Generation Sequencing technologies. RESULTS: Melon flies were reared on two diets at the larval stage, an artificial bran-based diet and on sweet gourd, which affected significantly the development of the bacterial profiles. Significant differentiation was also observed based on gender. The effect of radiation was mostly diet dependent, with irradiated melon flies reared on the bran diet exhibiting a significant reduction in species diversity and richness compared to their non-irradiated controls. Changes in the bacterial symbiome of the irradiated melon flies included a drastic reduction in the number of sequences affiliated with members of Citrobacter, Raoultella, and Enterobacteriaceae. At the same time, an increase was observed for members of Enterobacter, Providencia and Morganella. Interestingly, the irradiated male melon flies reared on sweet gourd showed a clear differentiation compared to their non-irradiated controls, namely a significant reduction in species richness and minor differences in the relative abundance for members of Enterobacter and Providencia. CONCLUSIONS: The two diets in conjunction with the irradiation affected significantly the formation of the bacterial symbiome. Melon flies reared on the bran-based artificial diet displayed significant changes in the bacterial symbiome upon irradiation, in all aspects, including species richness, diversity and composition. When reared on sweet gourd, significant changes occurred to male samples due to radiation, only in terms of species richness.

Detection and characterization of bacterial endosymbionts in Southeast Asian tephritid fruit fly populations.

BACKGROUND: Various endosymbiotic bacteria, including Wolbachia of the Alphaproteobacteria, infect a wide range of insects and are capable of inducing reproductive abnormalities to their hosts such as cytoplasmic incompatibility (CI), parthenogenesis, feminization and male-killing. These extended phenotypes can be potentially exploited in enhancing environmentally friendly methods, such as the sterile insect technique (SIT), for controlling natural populations of agricultural pests. The goal of the present study is to investigate the presence of Wolbachia, Spiroplasma, Arsenophonus and Cardinium among Bactrocera, Dacus and Zeugodacus flies of Southeast Asian populations, and to genotype any detected Wolbachia strains. RESULTS: A specific 16S rRNA PCR assay was used to investigate the presence of reproductive parasites in natural populations of nine different tephritid species originating from three Asian countries, Bangladesh, China and India. Wolbachia infections were identified in Bactrocera dorsalis, B. correcta, B. scutellaris and B. zonata, with 12.2-42.9% occurrence, Entomoplasmatales in B. dorsalis, B. correcta, B. scutellaris, B. zonata, Zeugodacus cucurbitae and Z. tau (0.8-14.3%) and Cardinium in B. dorsalis and Z. tau (0.9-5.8%), while none of the species tested, harbored infections with Arsenophonus. Infected populations showed a medium (between 10 and 90%) or low (< 10%) prevalence, ranging from 3 to 80% for Wolbachia, 2 to 33% for Entomoplasmatales and 5 to 45% for Cardinium. Wolbachia and Entomoplasmatales infections were found both in tropical and subtropical populations, the former mostly in India and the latter in various regions of India and Bangladesh. Cardinium infections were identified in both countries but only in subtropical populations. Phylogenetic analysis revealed the presence of Wolbachia with some strains belonging either to supergroup B or supergroup A. Sequence analysis revealed deletions of variable length and nucleotide variation in three Wolbachia genes. Spiroplasma strains were characterized as citri-chrysopicola-mirum and ixodetis strains while the remaining Entomoplasmatales to the Mycoides-Entomoplasmataceae clade. Cardinium strains were characterized as group A, similar to strains infecting Encarsia pergandiella. CONCLUSIONS: Our results indicated that in the Southeast natural populations examined, supergroup A Wolbachia strain infections were the most common, followed by Entomoplasmatales and Cardinium. In terms of diversity, most strains of each bacterial genus detected clustered in a common group. Interestingly, the deletions detected in three Wolbachia genes were either new or similar to those of previously identified pseudogenes that were integrated in the host genome indicating putative horizontal gene transfer events in B. dorsalis, B. correcta and B. zonata.

Cosolvent-Based Protein Pharmacophore for Ligand Enrichment in Virtual Screening.

Virtual screening of large compound databases, looking for potential ligands of a target protein, is a major tool in computer-aided drug discovery. Throughout the years, different techniques such as similarity searching, pharmacophore matching, or molecular docking have been applied with the aim of finding hit compounds showing appreciable affinity. Molecular dynamics simulations in mixed solvents have been shown to identify hot spots relevant for protein-drug interaction, and implementations based on this knowledge were developed to improve pharmacophore matching of small molecules, binding free-energy estimations, and docking performance in terms of pose prediction. Here, we proved in a retrospective manner that cosolvent-derived pharmacophores from molecular dynamics (solvent sites) improve the performance of docking-based virtual screening campaigns. We applied a biased docking scheme based on solvent sites to nine relevant target proteins that have a set of known ligands or actives and compounds that are, presumably, nonbinders (decoys). Our results show improvement in virtual screening performance compared to traditional docking programs both at a global level, with up to 35% increase in areas under the receiver operating characteristic curve, and in early stages, with up to a 7-fold increase in enrichment factors at 1%. However, the improvement in pose prediction of actives was less profound. The presented application makes use of the AutoDock Bias method and is the only cosolvent-derived pharmacophore technique that employs its knowledge both in the ligand conformational search algorithm and the final affinity scoring for virtual screening purposes.

Cloning of Dirac fermions in graphene superlattices.

Superlattices have attracted great interest because their use may make it possible to modify the spectra of two-dimensional electron systems and, ultimately, create materials with tailored electronic properties. In previous studies (see, for example, refs 1-8), it proved difficult to realize superlattices with short periodicities and weak disorder, and most of their observed features could be explained in terms of cyclotron orbits commensurate with the superlattice. Evidence for the formation of superlattice minibands (forming a fractal spectrum known as Hofstadter's butterfly) has been limited to the observation of new low-field oscillations and an internal structure within Landau levels. Here we report transport properties of graphene placed on a boron nitride substrate and accurately aligned along its crystallographic directions. The substrate's moiré potential acts as a superlattice and leads to profound changes in the graphene's electronic spectrum. Second-generation Dirac points appear as pronounced peaks in resistivity, accompanied by reversal of the Hall effect. The latter indicates that the effective sign of the charge carriers changes within graphene's conduction and valence bands. Strong magnetic fields lead to Zak-type cloning of the third generation of Dirac points, which are observed as numerous neutrality points in fields where a unit fraction of the flux quantum pierces the superlattice unit cell. Graphene superlattices such as this one provide a way of studying the rich physics expected in incommensurable quantum systems and illustrate the possibility of controllably modifying the electronic spectra of two-dimensional atomic crystals by varying their crystallographic alignment within van der Waals heterostuctures.

Effect of cement type on the clinical performance and complications of zirconia and lithium disilicate tooth-supported crowns: A systematic review. Report of the Committee on Research in Fixed Prosthodontics of the American Academy of Fixed Prosthodontics.

STATEMENT OF PROBLEM: Zirconia and lithium disilicate have been commonly used as materials for tooth-supported complete-coverage restorations. Adhesive and conventional cements have been suggested for cementation of these restorations. However, evidence on the effect of cement type on the clinical outcomes of teeth restored with zirconia or lithium disilicate restorations is unclear. PURPOSE: The purpose of this systematic review was to evaluate the clinical outcomes of teeth restored with zirconia or lithium disilicate restorations when adhesive or conventional cements are used. MATERIAL AND METHODS: This systematic review adopted the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered at the international prospective register of systematic reviews (PROSPERO) (CRD42018096493). An electronic search was performed in 2 databases (MEDLINE-PubMed and Cochrane Central), and a manual search, from January 2008 through January 2018. The primary clinical question was framed according to the Problem/Patient/Population, Intervention/Indicator, Comparison, Outcome (PICO) approach. The following question was the primary clinical question: "For patients requiring a single tooth-supported complete-coverage ceramic restoration, does adhesive cementation, as compared with conventional cementation, improve the clinical performance and limit the complications of this restoration?" The search included articles published in peer-reviewed journals in English and was limited to randomized clinical trials and prospective and retrospective clinical studies. RESULTS: Seventeen clinical studies met the eligibility criteria and were included for qualitative analysis. Included studies had 1280 participants who received 2436 zirconia and lithium disilicate crowns. The survival rates for adhesively cemented zirconia crowns ranged from 83.3% to 100%, whereas those reported for conventionally cemented zirconia crowns ranged from 82.0% to 100%. Survival rates for adhesively cemented lithium disilicate crowns ranged from 83.5% to 100%, whereas the survival rate reported for conventionally cemented lithium disilicate crowns was 98.5%. Commonly reported clinical complications included fracture of the veneering ceramic, crown fracture, and loss of crown retention. The mean follow-up time ranged from 25.5 months to 121.2 months. The studies that were assessed for risk of bias showed poor quality of evidence. CONCLUSIONS: Based on the available evidence and within the limitations of this systematic review, zirconia and lithium disilicate tooth-supported crowns exhibited comparable survival rates and complication patterns after adhesive or conventional cementation.

Multicentre study of laparoscopic or open assessment of the peritoneal cancer index (BIG-RENAPE).

BACKGROUND: The peritoneal cancer index (PCI) is a comparative prognostic factor for colorectal peritoneal metastasis (CRPM). The ability of laparoscopy to determine the PCI in consideration of cytoreductive surgery remains undetermined, and this study was designed to compare it with laparotomy. METHODS: A prospective multicentre study was conducted for patients with no known CRPM, but at risk of peritoneal disease. Surgery began with laparoscopic exploration followed by open exploration to determine the PCI. Concordance between laparoscopic and open assessment was evaluated for the diagnosis of CRPM and for the PCI. RESULTS: Among 50 patients evaluated, CRPM recurrence was found in 29 (58 per cent) and 34 (68 per cent) at laparoscopic and open surgery respectively. Laparoscopy was feasible in 88 per cent (44 of 50) and deemed satisfactory by the surgeon in 52 per cent (26 of 50). Among the 25 evaluable patients with satisfactory laparoscopy, there was concordance of 96 per cent (24 of 25 patients) and 38 per cent (10 of 25) for laparoscopic and open assessment of CRPM and the PCI respectively. Where there were discrepancies, it was laparoscopy that underestimated the PCI. CONCLUSION: Laparoscopy may underestimate the extent of CRPM.

Surgical variance between postconceptional and preconceptional minimally invasive transabdominal cerclage placement.

Recent data show that transabdominal cerclage placement via laparoscopy carries better obstetrical outcomes in comparison to transabdominal cerclage placement via laparotomy. In this surgical tutorial, we review the technique for minimally invasive abdominal cerclage and highlight the surgical differences between preconceptional and conceptional cerclage.