Passive Fit Analysis of Laser-Sintered, Three-Unit Implant Prostheses: An In Vitro Study.

PURPOSE: To assess if the implant-retained prostheses produced with laser-sintering technique present an accuracy and passive fit comparable to their milled counterpart. MATERIALS AND METHODS: Two regular neck Straumann analogs were placed in a block of PMMA 15 mm apart and parallel to each other. The PMMA block was then scanned and two groups of cobalt-chromium, screw-retained, three-unit implant prostheses were fabricated using milling (control) and laser-sintering (test) techniques. The prostheses were then screwed on the PMMA block and the vertical marginal gap between the prostheses and the analogs at the implant-abutment junction was measured twice, (1) when only one screw was tightened, and (2) when both screws were fully tightened. The average of each marginal gap measurement was compared to assess the difference in term of passive fit between the laser-sintered and the milled prostheses. RESULTS: The mean marginal gap of the milled and the laser-sintered groups were 23.18 µm (SD = 6.2) and 23.71 µm (SD = 19.5) respectively. CONCLUSIONS: Laser-sintered prostheses presented a marginal fit comparable to their milled counterpart and represent a clinically valid alternative to their milled counterpart. Int J Prosthodont 2023;36:e53-e60.

Independent co-delivery of model actives with different degrees of hydrophilicity from oil-in-water and water-in-oil emulsions stabilised by solid lipid particles via a Pickering mechanism: a-proof-of-principle study.

HYPOTHESIS: The development of vehicles for the co-encapsulation of actives with diverse characteristics and their subsequent controllable co-delivery is gaining increasing research interest. Predominantly centred around pharmaceutical applications, the majority of such co-delivery approaches have been focusing on solid formulations and less so on liquid-based systems. Simple emulsions can be designed to offer a liquid-based microstructural platform for the compartmentalised multi-delivery of actives. EXPERIMENTS: In this work, solid lipid nanoparticle stabilised Pickering emulsions were used for the co-encapsulation/co-delivery of two model actives with different degrees of hydrophilicity. Lipid particles containing a model hydrophobic active were prepared in the presence of either Tween 20 or whey protein isolate, and were then used to stabilise water-in-oil or oil-in-water emulsions, containing a secondary model active within their dispersed phase. FINDINGS: Solid lipid nanoparticles prepared with either type of emulsifier were able to provide stable emulsions. Release kinetic data fitting revealed that different co-delivery profiles can be achieved by controlling the surface properties of the lipid nanoparticles. The current proof-of-principle study presents preliminary data that confirm the potential of this approach to be utilised as a flexible liquid-based platform for the segregated co-encapsulation and independent co-release of different combinations of actives, either hydrophobic/hydrophilic or hydrophobic/hydrophobic, with diverse release profiles.

A natriuretic peptide from Arabidopsis thaliana (AtPNP-A) can modulate catalase 2 activity.

Analogues of vertebrate natriuretic peptides (NPs) present in plants, termed plant natriuretic peptides (PNPs), comprise a novel class of hormones that systemically affect salt and water balance and responses to plant pathogens. Several lines of evidence indicate that Arabidopsis thaliana PNP (AtPNP-A) affects cellular redox homeostasis, which is also typical for the signaling of its vertebrate analogues, but the molecular mechanism(s) of this effect remains elusive. Here we report identification of catalase 2 (CAT2), an antioxidant enzyme, as an interactor of AtPNP-A. The full-length AtPNP-A recombinant protein and the biologically active fragment of AtPNP-A bind specifically to CAT2 in surface plasmon resonance (SPR) analyses, while a biologically inactive scrambled peptide does not. In vivo bimolecular fluorescence complementation (BiFC) showed that CAT2 interacts with AtPNP-A in chloroplasts. Furthermore, CAT2 activity is lower in homozygous atpnp-a knockdown compared with wild type plants, and atpnp-a knockdown plants phenocopy CAT2-deficient plants in their sensitivity to elevated H2O2, which is consistent with a direct modulatory effect of the PNP on the activity of CAT2 and hence H2O2 homeostasis. Our work underlines the critical role of AtPNP-A in modulating the activity of CAT2 and highlights a mechanism of fine-tuning plant responses to adverse conditions by PNPs.

Influence of salt concentration on the formation of Pickering emulsions.

Here we study emulsification in a model experimental system comprised of water, an oil and colloidal particles. The particles are charge-stabilised colloidal silica; unsurprisingly, by varying the concentration of salt the degree of flocculation of the particles can be modified. The influence of salt on the formation of particle-stabilised oil droplets goes well beyond considerations of the colloidal stability of the particles. Our results demonstrate that the influence of salt on the particle-particle interaction is less important for emulsion formation than the influence of salt on both the particle wettability and the particle-interface interaction.

Epstein-Barr Virus Antibody Titers Are Not Associated with Gastric Cancer Risk in East Asia.

BACKGROUND: Epstein-Barr virus (EBV)-positive gastric cancers represent a distinct subtype of gastric cancers and account for nearly 10% of the gastric cancer burden, yet risk detection strategies for this cancer subtype are lacking. METHODS: We conducted a nested case-control study where we assayed 4 EBV antigens [viral capsid antigen (VCA), early antigen (EA), Epstein-Barr nuclear antigen (EBNA), and BZLF1-encoded replication activator protein (ZEBRA)] in either sera or plasma from 1447 gastric cancer cases and 1797 controls obtained from seven prospective cohorts representing individuals from the high gastric cancer-risk countries of China, Japan, and Korea. RESULTS: The prevalence of EBV sero-positivity was universal with the exception of one sero-negative individual, and the highest titers of the EBV antigens VCA (OR 0.95, 95% CI 0.78-1.17), EBNA (OR 0.88, 95% CI 0.72-1.08), EA (OR 0.97, 95% CI 0.79-1.19), and ZEBRA (OR 0.87, 95% CI 0.71-1.07) were not associated with risk of incident gastric cancer. When we stratified these data by H. pylori status, there was no change in the association. CONCLUSIONS: Multiplex serology of the aforementioned EBV antigens in serum may not be a suitable biomarker for predicting gastric cancer risk in East Asian populations.

Fabrication and Utilization of Bifunctional Protein/Polysaccharide Coprecipitates for the Independent Codelivery of Two Model Actives from Simple Oil-in-Water Emulsions.

Aside from single active microencapsulation, there is growing interest in designing structures for the coencapsulation and codelivery of multiple species. Although currently achievable within solid systems, significant challenges exist in realizing such functionality in liquid formulations. The present study reports on a novel microstructural strategy that enables the coencapsulation and corelease of two actives from oil-in-water emulsions. This is realized through the fabrication of sodium caseinate/chitosan (NaCAS/CS) complexes that in tandem function as encapsulants of one active (hydrophilic) but also as ("Pickering-like") stabilizers to emulsion droplets containing a secondary active (hydrophobic). Confocal microscopy confirmed that the two coencapsulated actives occupied distinct emulsion microstructure regions; the hydrophilic active was associated with the NaCAS/CS complexes at the emulsion interface, while the hydrophobic active was present within the oil droplets. Aided by their segregated coencapsulation, the two actives exhibited markedly different corelease behaviors. The hydrophilic active exhibited triggered release that was promoted by changes to pH, which weakened the protein-polysaccharide electrostatic interactions, resulting in particle swelling. The hydrophobic secondary active exhibited sustained release that was impervious to pH and instead controlled by passage across the interfacial barrier. The employed microstructural approach can therefore lead to the segregated coencapsulation and independent corelease of two incompatible actives, thus offering promise for the development of liquid-emulsion-based formulations containing multiple actives.

Are we missing hypoglycaemia? Elderly patients with insulin-treated diabetes present to primary care frequently with non-specific symptoms associated with hypoglycaemia.

INTRODUCTION: We assessed if patients with known hypoglycaemia present on other occasions with non-specific symptoms associated with (but not diagnosed as) hypoglycaemia, potentially representing missed hypoglycaemia. METHODS: 335 primary care records (5/2/12-4/2/13) from patients aged >65 (79 on insulin, 85 on sulphonylureas, 121 on metformin only, 50 without diabetes) were assessed for hypoglycaemia episodes and consultations with non-specific symptoms, "hypo clues". RESULTS: 27/79(34%) insulin-treated patients had >1 documented hypoglycaemia episode, compared to 4/85(5%) sulphonylurea-treated patients, 2/121(2%) metformin-only treated patients, and none without diabetes, p<0.001. "Hypo clue" consultations were common: 1.37 consultations/patient/year in insulin-treated patients, 0.98/patient/year in sulphonylurea-treated, 0.97/patient/year in metformin only-treated, and 0.78/patient/year in non-diabetic patients, p=0.34. In insulin-treated patients with documented hypoglycaemia, 20/27(74%) attended on another occasion with a "hypo clue" symptom, compared to 21/52(40%) of those without hypoglycaemia, p=0.008. No significant difference in the other treatment groups. Nausea, falls and unsteadiness were the most discriminatory symptoms: 7/33(21%) with hypoglycaemia attended on another occasion with nausea compared to 14/302(5%) without hypoglycaemia, p=0.002; 10/33(30%) vs 36/302(12%) with falls, p=0.007; and 5/33(15%) vs 13/302(4%) with unsteadiness, p=0.023. CONCLUSIONS: Non-specific symptoms are common in those >65 years. In insulin-treated patients at high hypoglycaemia risk, nausea, falls and unsteadiness should prompt consideration of hypoglycaemia.

The secret life of Pickering emulsions: particle exchange revealed using two colours of particle.

Emulsion droplets stabilised by colloidal particles (Pickering emulsions) can be highly stable, so it is unsurprising that they are beginning to be exploited industrially. The individual colloidal particles have interfacial attachment energies that are vastly larger than the thermal energy, hence they are usually thought of as being irreversibly adsorbed. Here we show, for the first time, particles being exchanged between droplets in a Pickering emulsion. This occurs when the emulsion contains droplets that share particles, often called bridging. By starting with two emulsions showing bridging, each stabilised by a different colour of particle, the dynamics can be studied as they are gently mixed together on a roller bank. We find that particle exchange occurs by two routes: firstly, during a period of unbridging and rebridging whose duration can be tuned by varying the wettability of the particles, and secondly, during very rare events when particles are ejected from one droplet and re-adsorbed onto another.

British Society of Prosthodontics Debate on the Implications of the Minamata Convention on Mercury to Dental Amalgam--Should our Patients be Worried?.

In 2013, the Minamata Convention on Mercury called for a global phase-down of amalgam use, with a view to reduce environmental mercury pollution. This will significantly impact UK dentistry, given the still extensive use of amalgam in U.K. general dental practice. However, until now there has been little national discussion or debate. In Spring 2015, The British Society of Prosthodontics dedicated a significant part of its Annual Conference to debating the implications of this issue. Clinical case examples were discussed with audience interaction and voting facilitated using innovative Audience Response System Technology. A remarkable range of concerns and opinions were given. The debate elicited specific concerns amongst clinicians regarding the suitability of mercury-free alternatives to amalgam; particularly where cavities are large and extend beneath the gingival anatomy. There are also anecdotal reports of Dental Foundation (DF) dentists not being adequately taught the use of dental amalgam in undergraduate dental schools. CPD/CLINICAL RELEVANCE: Many clinicians, especially those treating patients for whom moisture control is challenging, feel that amalgam should remain available for clinicians to choose in certain clinical circumstances for the restoration of posterior teeth, even in the event of a complete phase-down.

Making and breaking bridges in a Pickering emulsion.

HYPOTHESIS: Particle bridges form in Pickering emulsions when the oil-water interfacial area generated by an applied shear is greater than that which can be stabilised by the available particles and the particles have a slight preference for the continuous phase. They can subsequently be broken by low shear or by modifying the particle wettability. EXPERIMENTS: We have developed a model oil-in-water system for studying particle bridging in Pickering emulsions stabilised by fluorescent Stöber silica. A mixture of dodecane and isopropyl myristate was used as the oil phase. We have used light scattering and microscopy to study the degree to which emulsions are bridged, and how this is affected by parameters including particle volume fraction, particle wettability and shear rate. We have looked for direct evidence of droplets sharing particles using freeze fracture scanning electron microscopy. FINDINGS: We have created strongly aggregating Pickering emulsions using our model system. This aggregating state can be accessed by varying several different parameters, including particle wettability and particle volume fraction. Particles with a slight preference for the continuous phase are required for bridging to occur, and the degree of bridging increases with increasing shear rate but decreases with increasing particle volume fraction. Particle bridges can subsequently be removed by applying low shear or by modifying the particle wettability.

Love thy neighbour or opposites attract? Patterns of spatial segregation and association among crested penguin populations during winter.

AIM: Competition for food among populations of closely related species and conspecifics that occur in both sympatry and parapatry can be reduced by interspecific and intraspecific spatial segregation. According to predictions of niche partitioning, segregation is expected to occur at habitat boundaries among congeners and within habitats among conspecifics, while negative relationships in the density of species or populations will occur in areas of overlap. We tested these predictions by modelling the winter distributions of two crested penguin species from three colonies in the south-western Atlantic. LOCATION: Penguins were tracked from two large colonies on the Falkland Islands and one in South Georgia, from where they dispersed through the South Atlantic, Southern Ocean and south-eastern Pacific. METHODS: Forty macaroni penguins (Eudyptes chrysolophus) from South Georgia and 82 southern rockhopper penguins (Eudyptes chrysocome chrysocome) from two colonies in the Falkland Islands were equipped with global location sensors which log time and light, allowing positions to be estimated twice-daily, from April to August in 2011. Positions were gridded and converted into maps of penguin density. Metrics of overlap were calculated and density was related to remote-sensed oceanographic variables and competitor density using generalized additive models. RESULTS: Macaroni penguins from western South Georgia and southern rockhopper penguins from Steeple Jason Island, Falkland Islands, were spatially segregated by differences in their habitat preferences thus supporting our first prediction regarding interspecific segregation. However, southern rockhopper penguins from Beauchêne Island showed a marked spatial overlap with macaroni penguins as the two had similar habitat preferences and strong mutual associations when controlling for habitat. Contrary to our predictions relating to intraspecific segregation, southern rockhopper penguins from Beauchêne Island and Steeple Jason Island were segregated by differences in habitat selection. MAIN CONCLUSIONS: Morphological differentiation probably allows macaroni penguins from South Georgia and southern rockhopper penguins from Beauchêne Island to coexist in areas of spatial overlap, whereas segregation of the two Falkland rockhopper penguin populations may have arisen from two distinct lineages retaining cultural fidelity to ancestral wintering areas.

Effects of α-tocopherol and ß-carotene supplementation on cancer incidence and mortality: 18-year postintervention follow-up of the Alpha-tocopherol, Beta-carotene Cancer Prevention Study.

In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50-69 years, daily α-tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas ß-carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α-tocopherol and ß-carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post-trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96-1.11) among ß-carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89-1.05) among α-tocopherol recipients compared with nonrecipients with the preventive effect of α-tocopherol continuing ∼8 years postintervention. Body mass index significantly modified the effect of α-tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88-1.14) in normal-weight men, 0.87 (95% CI, 0.77-0.98) in overweight men, and 1.25 (95% CI, 1.01-1.55) in obese men. The post-trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98-1.05) for α-tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99-1.05) for ß-carotene recipients compared with nonrecipients. α-Tocopherol decreased post-trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70-0.99), whereas ß-carotene increased it (RR, 1.20; 95% CI, 1.01-1.42). In conclusion, supplementation with α-tocopherol and ß-carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate-dose α-tocopherol on prostate cancer continued several years post-trial and resulted in lower prostate cancer mortality.

Effects of ambient temperature on egg and larval development of the invasive emerald ash borer (Coleoptera: Buprestidae): implications for laboratory rearing.

The emerald ash borer, Agrilus planipennis Fairmaire, an invasive beetle from Asia causing large scale ash (Fraxinus) mortality in North America, has been extremely difficult to rear in the laboratory because of its long life cycle and cryptic nature of immature stages. This lack of effective laboratory-rearing methods has not only hindered research into its biology and ecology, but also mass production of natural enemies for biological control of this invasive pest. Using sticks from the alternate host plant, Fraxinus uhdei (Wenzig) Lingelsh, we characterized the stage-specific development time and growth rate of both emerald ash borer eggs and larvae at different constant temperatures (12-35 degrees C) for the purpose of developing effective laboratory-rearing methods. Results from our study showed that the median time for egg hatching decreased from 20 d at 20 degrees C to 7 d at 35 degrees C, while no emerald ash borer eggs hatched at 12 degrees C. The developmental time for 50% of emerald ash borer larvae advancing to third, fourth, and J-larval stages at 20 degrees C were 8.3, 9.1, and 12.3 wk, respectively, approximately two times longer than at 30 degrees C for the corresponding instars or stages. In contrast to 30 degrees C, however, the development times of emerald ash borer larvae advancing to later instars (from oviposition) were significantly increased at 35 degrees C, indicating adverse effects of this high temperature. The optimal range of ambient temperature to rear emerald ash borer larvae should be between 25-30 degrees C; however, faster rate of egg and larval development should be expected as temperature increases within this range.

A gene expression signature from peripheral whole blood for stage I lung adenocarcinoma.

Affordable early screening in subjects with high risk of lung cancer has great potential to improve survival from this deadly disease. We measured gene expression from lung tissue and peripheral whole blood (PWB) from adenocarcinoma cases and controls to identify dysregulated lung cancer genes that could be tested in blood to improve identification of at-risk patients in the future. Genome-wide mRNA expression analysis was conducted in 153 subjects (73 adenocarcinoma cases, 80 controls) from the Environment And Genetics in Lung cancer Etiology study using PWB and paired snap-frozen tumor and noninvolved lung tissue samples. Analyses were conducted using unpaired t tests, linear mixed effects, and ANOVA models. The area under the receiver operating characteristic curve (AUC) was computed to assess the predictive accuracy of the identified biomarkers. We identified 50 dysregulated genes in stage I adenocarcinoma versus control PWB samples (false discovery rate ≤0.1, fold change ≥1.5 or ≤0.66). Among them, eight (TGFBR3, RUNX3, TRGC2, TRGV9, TARP, ACP1, VCAN, and TSTA3) differentiated paired tumor versus noninvolved lung tissue samples in stage I cases, suggesting a similar pattern of lung cancer-related changes in PWB and lung tissue. These results were confirmed in two independent gene expression analyses in a blood-based case-control study (n = 212) and a tumor-nontumor paired tissue study (n = 54). The eight genes discriminated patients with lung cancer from healthy controls with high accuracy (AUC = 0.81, 95% CI = 0.74-0.87). Our finding suggests the use of gene expression from PWB for the identification of early detection markers of lung cancer in the future.