Contralateral Nodal Relapse in Well-lateralised Oral Cavity Cancers Treated Uniformly with Ipsilateral Surgery and Adjuvant Radiotherapy With or Without Concurrent Chemotherapy: a Retrospective Study.

AIMS: To evaluate the incidence and pattern of contralateral nodal relapse (CLNR), contralateral nodal relapse-free survival (CLNRFS) and risk factors predicting CLNR in well-lateralised oral cavity cancers (OCC) treated with unilateral surgery and adjuvant ipsilateral radiotherapy with or without concurrent chemotherapy. MATERIALS AND METHODS: Consecutive patients of well-lateralised OCC treated between 2012 and 2017 were included. The primary endpoint was incidence of CLNR and CLNRFS. Univariable and multivariable analyses were carried out to identify potential factors predicting CLNR. RESULTS: Of the 208 eligible patients, 21 (10%) developed isolated CLNR at a median follow-up of 45 months. The incidence of CLNR was 21.3% in node-positive patients. CLNR was most common at level IB (61.9%) followed by level II. The 5-year CLNRFS and overall survival were 82.5% and 57.7%, respectively. Any positive ipsilateral lymph node (P = 0.001), two or more positive lymph nodes (P < 0.001), involvement of ipsilateral level IB (P = 0.002) or level II lymph node (P < 0.001), presence of extranodal extension (P < 0.001), lymphatic invasion (P = 0.015) and perineural invasion (P = 0.021) were significant factors for CLNR on univariable analysis. The presence of two or more positive lymph nodes (P < 0.001) was an independent prognostic factor for CLNR on multivariable analysis. CLNR increased significantly with each increasing lymph node number beyond two compared with node-negative patients. CONCLUSION: The overall incidence of isolated CLNR is low in well-lateralised OCC. Patients with two or more positive lymph nodes have a higher risk of CLNR and may be considered for elective treatment of contralateral neck.

Challenges in the Sustainability of Brachytherapy Service in Contemporary Radiotherapy.

Brachytherapy has a long history of delivering a highly conformal radiation dose to the target volume with sparing of adjacent normal tissue and has an irreplaceable role in certain cancers, such as cervical and prostate cancers. There have been futile attempts to replace brachytherapy with other radiation techniques. Despite that there are multifaceted challenges in preserving this dying art, from establishment, to a trained workforce, to maintenance of the equipment and source replacement costs. Here we focus on the challenges to access brachytherapy, the availability and distribution of care across the globe and appropriate training leading to proper implementation of the procedure. Brachytherapy holds a significant place in the treatment armamentarium of most common cancers, such as cervical, prostate, head and neck and skin cancers. However, there is an uneven distribution of brachytherapy facilities, not only across the globe, but also at a national level, with a larger proportion of facilities concentrated in certain regions, more so in low and low-middle income countries. The regions with the highest incidence of cervical cancer have the least access to brachytherapy facilities. Attempts to bridge the gap are essential and should be focused on uniform distribution and access to care, improving training of the workforce through specialised training programmes, reducing the cost of care, planning to reduce the recurring cost, generating evidence and research guidelines, renewing interest in brachytherapy through rebranding, use of social media and building an attainable long-term roadmap.

Non-surgical organ preservation in laryngeal and hypopharyngeal cancers: an audit from the clinic.

BACKGROUND: There is increasing concern regarding efficacy of organ preservation protocol in laryngeal and hypopharyngeal cancers. METHOD: This study retrospectively assessed disease-related and functional outcomes of 191 patients with non-metastatic laryngeal or hypopharyngeal squamous cell carcinoma treated with curative intent (radiotherapy with or without chemotherapy). RESULTS: Seventy-six patients (39.8 per cent) had a primary cancer in the larynx, and 115 patients (60.2 per cent) had a primary cancer in the hypopharynx. The median follow up was 39 months. The 3-year time to progression, overall survival, local control and laryngectomy free survival was 56.2 per cent, 76.3 per cent, 73.2 per cent and 67.2 per cent, respectively. At the time of analysis, 83 patients (43.5 per cent) were alive and disease free at their last follow up and did not require tube feeding or tracheostomy. The laryngo-oesophageal dysfunction-free survival was 61 per cent at 3 years. CONCLUSION: Organ conservation protocols remain the standard of treatment in appropriately selected patients with laryngeal and hypopharyngeal cancers.

Concurrent Cetuximab-based bioradiotherapy versus Cisplatin-based Chemoradiotherapy in the Definitive Management of Favourable Biology Human Papillomavirus-associated Oropharyngeal Squamous Cell Carcinoma: Systematic Review and Meta-analysis.

Replacing cisplatin with cetuximab concurrently during radiotherapy has been one of the strategies of treatment de-escalation in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). However, until recently, there were limited data on the efficacy and safety of such an approach. A systematic search of the literature was carried out to identify prospective randomised controlled trials comparing definitive cisplatin-based chemoradiotherapy (CT-RT) versus cetuximab-based bioradiotherapy (BRT) in HPV-positive OPSCC. Overall survival and locoregional control were primary outcomes of interest; rates of acute and late toxicities (≥grade 3) were secondary end points. Outcome data were aggregated using a random-effects model as per Cochrane methodology including risk of bias assessment and expressed as hazard ratio or risk ratio as appropriate with respective 95% confidence intervals. Data from five randomised controlled trials involving 1560 patients with HPV-positive OPSCC were aggregated in the meta-analysis. Cetuximab-based BRT was associated with a significantly increased risk of death (hazard ratio = 2.83, 95% confidence interval 1.22-6.57; P = 0.02) and locoregional relapse (hazard ratio = 2.78, 95% confidence interval 1.77-4.39; P < 0.0001) compared with cisplatin-based CT-RT. Cisplatin was associated with higher rates of acute ≥grade 3 toxicity in terms of acute kidney injury, dry mouth, febrile neutropenia, hearing impairment, nausea and vomiting, whereas dermatitis and acneiform rash were more common with cetuximab. There were no significant differences in overall rates of late ≥grade 3 toxicity (risk ratio = 0.63, 95% confidence interval = 0.36-1.10; P = 0.10). In conclusion, there is moderate-certainty evidence that cetuximab-based BRT leads to inferior efficacy outcomes compared with cisplatin-based CT-RT in the definitive curative-intent management of HPV-associated OPSCC.

Post-cricoid and Upper Oesophagus Cancers Treated with Organ Preservation Using Intensity-modulated Image-guided Radiotherapy: a Phase II Prospective Study of Outcomes, Toxicity and Quality of Life.

AIMS: To prospectively examine the outcomes, toxicity and quality of life (QoL) of patients with post-cricoid and upper oesophagus (PCUE) cancers treated with an organ-preservation approach of (chemo)-radiotherapy using intensity-modulated image-guided radiotherapy (IM-IGRT). MATERIALS AND METHODS: This phase II prospective study was conducted at a tertiary cancer centre from February 2017 to January 2020. Forty patients with squamous cell carcinoma of PCUE of stage T1-3, N0-2, M0 were accrued. Gross exolaryngeal extension/dysfunctional larynx were major exclusion criteria. Patients received 63-66 Gy in once-daily fractions using volumetric modulated arc therapy with daily IGRT. Outcome measures included disease-related outcomes, patterns of failure, Radiation Therapy Oncology Group toxicities, feeding tube dependency and QoL. RESULTS: The median follow-up was 22 months. Twenty-six (87.5%) patients had locoregionally advanced disease and 34 (85%) patients received (chemo)-radiotherapy. A complete response was observed in 26 (65%) patients. The 2-year locoregional control, event-free survival and cause-specific survival were 59.6%, 40.2% and 44.8%, respectively. The volume of primary tumour (GTVPvol) exceeding 28 cm3 had inferior overall survival (P = 0.005) on univariate analysis. Multivariable analysis showed GTVPvol and positron emission tomography-computed tomography maximum standardised uptake value to be independently predictive for event-free and overall survival. A feeding tube requirement at presentation was seen in 11 (27.5%) patients, whereas long-term feeding tube dependency at 6 months was seen in 10 (37%) patients. For QoL, a statistical improvement in pain, appetite loss and swallowing was observed over time. CONCLUSION: Although the outcomes of PCUE cancers remain dismal, the use of state of the art diagnostic modalities, careful case selection and modern radiotherapy techniques improved outcomes as compared with before in this exclusive analysis of PCUE cancers.

Indentation of the cornea: A Bi-layer contact problem.

Histological observations of the cornea have identified the presence of multiple layers with differing thickness and function. The composition of the cornea consists primarily of collagen fibrils held together with proteoglycans but with an aqueous interstitial component being dominant. Indentation provides a means to quantify the spatial variation of the mechanical properties of the cornea, however the role of the different layers on the indentation response has barely been addressed. In addition, the response of the fluid content and its displacement during indentation has not been adequately considered. In this study indentation of the cornea with a relatively large spherical tipped indenter (R = 500 µm) is considered. It was observed that the initial phase of loading did not fit a classic Hertz elastic response but showed an initial steeper slope that gradually declines with increasing force and displacement. A relatively simple approach is developed that initially considers the cornea as a poro-elastic bi-layer contact problem, that is the presence of an outer thin stiffer Bowman's layer overlaying the thicker less stiff stroma.

Resequencing and signatures of selection scan in two Siberian native sheep breeds point to candidate genetic variants for adaptation and economically important traits.

Russian sheep breeds represent an important economic asset by providing meat and wool, whilst being adapted to extreme climates. By resequencing two Russian breeds from Siberia: Tuva (n = 20) and Baikal (n = 20); and comparing them with a European (UK) sheep outgroup (n = 14), 41 million variants were called, and signatures of selection were identified. High-frequency missense mutations on top of selection peaks were found in genes related to immunity (LOC101109746) in the Baikal breed and wool traits (IDUA), cell differentiation (GLIS1) and fat deposition (AADACL3) in the Tuva breed. In addition, genes found under selection owing to haplotype frequency changes were related to wool traits (DSC2), parasite resistance (CLCA1), insulin receptor pathway (SOCS6) and DNA repair (DDB2) in the Baikal breed, and vision (GPR179) in the Tuva breed. Our results present candidate genes and SNPs for future selection programmes, which are necessary to maintain and increase socioeconomic gain from Siberian breeds.

Near-Infrared Spectroscopy Reveals Brain Hypoxia and Cerebrovascular Dysregulation in Primary Biliary Cholangitis.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease linked to symptoms including fatigue and altered mood/cognition, indicating that chronic liver inflammation associated with PBC can impact brain function. We employed near-infrared spectroscopy (NIRS), a noninvasive neuroimaging technique, to determine whether patients with PBC exhibit reduced cerebral oxygen saturation (StO2 ) and altered patterns of microvascular cerebral blood perfusion and whether these alterations were associated with clinical phenotype. This observational case-control study was conducted at a tertiary hospital clinic (University of Calgary Liver Unit). APPROACH AND RESULTS: Thirteen female patients with noncirrhotic PBC, seven female patients with cirrhotic PBC, and 11 healthy female controls were recruited by physician referral and word of mouth, respectively. NIRS was used to measure cerebral hemoglobin and oxygen saturation. A wavelet phase coherence method was used to estimate the coherent frequency coupling of temporal changes in cerebral hemodynamics. The PBC group demonstrated significantly reduced cerebral StO2 (P = 0.01, d = 0.84), indicating cerebral hypoxia, significantly increased cerebral deoxygenated hemoglobin concentration (P < 0.01, d = 0.86), and significantly reduced hemodynamic coherence in the low-frequency band (0.08-0.15 Hz) for oxygenated hemoglobin concentration (P = 0.02, d = 0.99) and total hemoglobin (tHb) concentration (P = 0.02, d = 0.50), indicating alterations in cerebrovascular activity. Complete biochemical response to ursodeoxycholic acid (UDCA) therapy in early patients with PBC was associated with increased cerebral tHb concentration and decreased hemodynamic coherence. CONCLUSIONS: Using NIRS, patients with PBC were found to have hypoxia, increased cerebral hemoglobin concentration, and altered cerebrovascular activity, which were reversed in part in UDCA responders. In addition, symptoms and quality-of-life measures did not correlate with brain hypoxia or cerebrovascular dysregulation in patients with PBC.

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort.

AIMS: To report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. MATERIALS AND METHODS: Between January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow-up of 37 months (range: 7-110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. CONCLUSION: ICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Size or hierarchical dependence of the elastic modulus of three ceramic-composite CAD/CAM materials.

OBJECTIVE: To measure the elastic modulus of three ceramic-composite CAD/CAM materials at three different microstructural dimensions: macro, micro, and nano. METHODS: Three novel ceramic-composite CAD/CAM materials (Enamic, Lava Ultimate, and Cerasmart) were investigated. Rectangular cross-sections 10 × 5.7 × 1 mm3 (n = 30) were cut from standard sized milling blocks of each material prior to polishing. Specimens were macro-tested using three-point bending and with a dynamic mechanical analyzer (DMA), micro-tested using a nano-indentation system, and finally at the nano-level with an atomic force microscope (AFM). Data were analyzed with 1-way ANOVA (α = 0.05). RESULTS: At the macro level Enamic showed the highest elastic modulus, followed by Lava Ultimate and Cerasmart respectively (p < 0.001). Measurements at the micro and nano level resulted in bimodal distributions of the elastic modulus values associated with the various phases present with values higher and lower than measured at the macro level. Only at the nano-level were the various phases of Cerasmart able to be distinguished. CONCLUSIONS: The tested materials showed different elastic modulus at the different size or hierarchical levels that enabled comparison with the hierarchical values of enamel. SIGNIFICANCE: Studying the mechanical properties of these novel materials at different size or hierarchical scales can help to understand their potential clinical performance, such as structural durability and opposing tooth wear and lead to more biomimetic like dental restorative materials.

Homogeneous and heterogeneous populations of active rods in two-dimensional channels.

Active swarms, consisting of individual agents which consume energy to move or produce work, are known to generate a diverse range of collective behaviors. Many examples of active swarms are biological in nature (e.g., fish shoals and bird flocks) and have been modeled extensively by numerical simulations. Such simulations of swarms usually assume that the swarm is homogeneous; that is, every agent has exactly the same dynamical properties. However, many biological swarms are highly heterogeneous, such as multispecies communities of micro-organisms in soil, and individual species may have a wide range of different physical properties. Here we explore heterogeneity by developing a simple model for the dynamics of a swarm of motile heterogeneous rodlike bacteria in the absence of hydrodynamic effects. Using molecular dynamics simulations of active rods confined within a two-dimensional rectangular channel, we first explore the case of homogeneous swarms and show that the key parameter governing both dynamics is ratio of the motility force to the steric force. Next we explore heterogeneous or mixed swarms in which the constituent self-propelled rods have a range of motilities and steric interactions. Our results show that the confining boundaries play a strong role in driving the segregation of mixed populations.

The dehydration effect on mechanical properties of tooth enamel.

Exploring the subtle mechanical property changes of tooth enamel in different conditions is important for dental research. However, some experimental results can be deceptive and may lead to misunderstanding. In particular, we show the dehydration associated with increased mechanical properties of tooth enamel as monitored by Nanomechanical System Testing (NST) can be misleading. The results indicate that the friction coefficient decreased with an increase of hardness of enamel upon dehydration, which appears to imply that dehydrated enamel has better mechanical properties than hydrated enamel. However, more critical scrutiny of the actual situation, suggests dehydrated teeth enamel are more prone to damage and greater wear. To appreciate the basis for the contrast between the experimental results and reality of natural hydrated enamel, which has better resistance to wear, and is critical for an understanding of the aetiology of enamel resistance to fracture.

Thermal induced deflection of a porcelain-zirconia bilayer: Influence of cooling rate.

OBJECTIVE: To determine the thermal expansion of a porcelain (VM9) and tetragonal zirconia (Y-TZP) as well as the deflection upon re-heating and cooling of a bilayer fabricated from these two materials after slow and rapid cooling during initial fabrication. METHODS: The coefficient of thermal expansion (CTE) of bulk porcelain and Y-TZP as well as bilayer beam deflection was measured with a novel non-contact optical dilatometer. The influence of cooling rate during initial fabrication of the porcelain-zirconia bilayer and the bulk porcelain during subsequent heating and cooling is investigated. Specimens were heated to 900°C in the dilatometer, well in excess of the glass transition temperature (Tg) and softening temperature (Ts) of the porcelain. RESULTS: The thermal expansion of the porcelain above Tg exhibits a threefold increase in CTE over that observed below Tg. Observations of the bilayer deflection reflect the difference in the CTE of the component materials and enable Tg and Ts temperatures for the porcelain to be estimated. Initial cooling rate of the porcelain and porcelain-YTZP bilayer was found to have a profound influence on the subsequent response to slow reheating and cooling as well as the resultant residual deflection. SIGNIFICANCE: The estimation of the residual stress and potential for chipping of porcelain-zirconia dental restorative systems should not be based solely on thermal expansion data measured below Tg.

Frictional coefficient during flossing of teeth.

OBJECTIVE: This in-vitro study aimed to develop a technique to measure the frictional forces and determine the frictional coefficient (µ) associated with the rubbing of dental floss against teeth. Incorrect flossing technique and the etiology of grooves at the cementoenamel junction (CEJ) of proximal area of teeth has long been a controversial topic. We hypothesized that the µ between teeth surfaces and dental floss is affected by contact angulation. MATERIALS AND METHODS: Tests were conducted using two different types of dental floss (waxed and unwaxed nylon) on different surfaces (enamel, dentine, smooth and rough glass rods) under different moisture conditions (dry and wet). The µ generated by performing C-shape flossing was measured, using the Capstan equation, at constant load (100g) over different flossing contact sliding angulations. In addition, the surface characteristics of intact and used nylon flosses were compared using a scanning electron microscope (SEM). RESULTS: The mean µ was highest with a smooth glass rod (0.42±0.11), followed by rough glass rods (0.30±0.07), dry enamel (0.27±0.08), wet enamel (0.23±0.06), then dentine (0.18±0.04). Moreover, higher µ was associated with waxed floss when used against dry enamel, smooth and rough glass rods (P<0.001). At different moisture conditions, waxed floss demonstrated greater µ with dry surfaces (P<0.03). No association was found between µ and dental floss contact angulation. Both floss types showed deterioration after usage; although waxed type exhibited markedly greater deterioration when used on dry surfaces. In conclusion, the magnitude of the µ was found to be influenced by surface roughness, moisture condition, and independent of the contact angulation area during sliding of dental floss. SIGNIFICANCE: It is important to consider the potential side effects of frictional forces on both tooth surface and dental floss during clinical application.

FTIR characterization of the setting reaction of biodentine™.

OBJECTIVE: To provide insight of the setting reactions of Biodentine™, a hydraulic calcium silicate cement, based upon observations using Fourier Transform Infra-Red (FTIR) spectroscopy. METHODS: FTIR spectra of components before and during the setting reaction were taken using the attenuated total reflectance (ATR) technique. Measurements over wavelengths 600-4000cm-1 were taken at regular intervals for two days. RESULTS: FTIR spectrum of Biodentine™ powder revealed a number of peaks from 650 to 1100cm-1 and a plateau from 1400 to 1500cm-1, indicative of SiO and CO3-bonding, while the mixing fluid exhibited water peaks. Results following mixing displayed three distinct regimes; (i) incubation phase, during the first 35min, when minimal change occurred, (ii) rapid transitory stage, between 35 and 90min, when major changes occurred, and (iii) slow sustained reaction stage for remaining 45h. Incubation appears to be associated with the presence of CO3-peaks. The transition region indicates formation of CaOH and Jennite OH-peaks, anticipated intermediate reaction phases. At 90min, the end of second stage, CaOH and Jennite are replaced by a dominant Portlandite (Ca(OH)2)-peak and minor presence of Tobermorite, another anticipated intermediate phase, and water reduction. During the following 45h Portlandite and Tobermorite decline while the water peak increases. SIGNIFICANCE: FTIR can be used to follow the chemical reactions in dental cements and provides insight into the relatively slow setting reactions of hydraulic calcium silicate cements.

Synthesis of stabilized hydroxyapatite nanosuspensions for enamel caries remineralization.

BACKGROUND: The aim of this study was to develop and evaluate a method for synthesizing a stable suspension of hydroxyapatite nanoparticles and to test its efficacy for remineralizing carious enamel lesions. METHODS: Hydroxyapatite (HA) particles were synthesized using wet chemistry. Synthesized particles were introduced into a high-pressure homogenizer (5-10 homogenization passes at 15 000 psi) in the presence of different stabilizers. Size and distribution of the resultant particles were determined using dynamic light scattering (DLS). The morphology and composition of the nanoparticles were determined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS). Subsequently, artificial lesions were treated with HA nanosuspension plus artificial saliva or a fluoride-containing artificial saliva only. Visual analysis and quantification of the lesion mineral density before and after remineralization were performed using microcomputed tomography. RESULTS: DLS and SEM results confirmed the formation of nonagglomerated HA nanoparticles (20-40 nm) following high-pressure homogenization treatment. Quantitative evaluation of the lesions showed that remineralization of the lesion with hydroxyapatite nanosuspension led to a significantly higher level of mineral gain compared to the control group (P < 0.05). CONCLUSION: High-pressure homogenization is an effective method for facile preparation of a stable suspension of hydroxyapatite nanoparticles. Treatment of artificial lesions with nonagglomerated spherical HA nanoparticles improves the remineralization of enamel lesion.

Influence of ageing on glass and resin bonding of dental glass-ceramic veneer adhesion to zirconia: A fracture mechanics analysis and interpretation.

Adhesion plays a major role in the bonding of dental materials. In this study the adhesion of two glass-ceramic systems (IPS e.max and VITABLOCS) to a zirconia sintered substrate using a glass (for IPS e.max) and resin (VITABLOCS) before and after exposure to ageing for 14 days in distilled water at 37 °C are compared using two interfacial fracture mechanics tests, the 3 point bend Schwickerath (Kosyfaki and Swain, 2014; Schneider and Swain, 2015) and 4 point bend (Charalambides et al., 1989) approaches. Both tests result in stable crack extension from which the strain energy release rate (G, N/m or J/m2) can be determined. In the case of the 3 PB test the Work of Fracture was also determined. In addition, the Schwickerath test enables determination of the critical stress for the onset of cracking to occur, which forms the basis of the ISO (ISO9693-2:2016) adhesion test for porcelain ceramic adhesion to zirconia. For the aged samples there was a significant reduction in the resin-bonded strengths (Schwickerath) and strain energy release rate (both 3 and 4 PB tests), which was not evident for the glass bonded specimens. Critical examination of the force-displacement curves showed that ageing of the resin resulted in a major change in the form of the curves, which may be interpreted in terms of a reduction in the critical stress to initiate cracking and also in the development of an R-curve. The extent of the reduction in strain energy release rate following ageing was greater for the Schwickerath test than the Charalambides test. The results are discussed in terms of; the basic mechanics of these two tests, the deterioration of the resin bonding following moisture exposure and the different dimensions of the specimens. These in-vitro results raise concerns regarding resin bonding to zirconia. STATEMENT OF SIGNIFICANCE: The present study uses a novel approach to investigate the role of ageing or environmental degradation on the adhesive bonding of two dental ceramics to zirconia. This continues to be a major clinical problem but current approaches, till now, have relied upon a myriad of strength based tests to quantify the extent of environmental degradation with time. In this paper we use two fracture mechanics approaches, based upon simple 3 and 4 point bend testing procedures that enable stable debonding crack extension to occur. The paper provides a more critical approach to evaluate the role of environmental degradation of adhesion for dental materials.

Tenofovir disoproxil fumarate significantly decreases serum lipoprotein levels compared with entecavir nucleos(t)ide analogue therapy in chronic hepatitis B carriers.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are first-line treatments for chronic hepatitis B (CHB). Studies suggest lipid lowering effect of TDF in human immunodeficiency virus positive (HIV+) individuals, but the effect on lipids and cardiovascular disease (CVD) risk in CHB is unknown. AIM: To compare TDF vs ETV effects on lipid levels in CHB. METHODS: In this retrospective cohort study, data on serum lipids and CVD risk factors at baseline and ~1 year on TDF or ETV were collected from CHB carriers. We used propensity score matched models to assess the effect on total cholesterol (TC), LDL-C, HDL and triglycerides (TGL). RESULTS: In 348 patients, median age was 57 (IQR: 47-65 years), 63% were male, 77% were Asian, 19% were cirrhotic, 25% were HBeAg positive at baseline, and 72% received TDF vs 28% ETV. ETV-treated patients were older (median age: 60 vs 55, P<.01), had similar smoking and hypertension rates, but diabetes and dyslipidemia were more prevalent (19% vs 9%, P=.01; 14% vs 6%, P=.05, respectively). In propensity score matched models for age, gender, usage of lipid lowering agents, dyslipidemia and diabetes, TDF-treated patients were more likely to show a 20% decrease in TC (95% CI: 3%-25%), LDL-C (95% CI: 1%-25%) and HDL-C (CI: 10%-30%) levels compared with those on ETV. No change in TGL was observed in either group. CONCLUSIONS: A greater decline in TC, LDL-C and HDL was observed in CHB carriers receiving TDF compared with ETV. These data may influence anti-viral choice in CHB carriers at risk for CVD.

Comparison of three and four point bending evaluation of two adhesive bonding systems for glass-ceramic zirconia bi-layered ceramics.

OBJECTIVES: To quantify the adhesion of two bonding approaches of zirconia to more aesthetic glass-ceramic materials using the Schwickerath (ISO 9693-2:2016) three point bend (3PB) [1] test to determine the fracture initiation strength and strain energy release rate associated with stable crack extension with this test and the Charalamabides et al. (1989) [2] four point bend (4PB) test. METHODS: Two glass-ceramic materials (VITABLOCS Triluxe forte, Vita Zahnfabrik, Germany and IPS.emax CAD, Ivoclar Vivadent, Liechtenstein) were bonded to sintered zirconia (VITA InCeram YZ). The former was resin bonded using a dual-cure composite resin (Panavia F 2.0, Kuraray Medical Inc., Osaka, Japan) following etching and silane conditioning, while the IPS.emax CAD was glass bonded (IPS e.max CAD Crystall/Connect) during crystallization of the IPS.emax CAD. Specimens (30) of the appropriate dimensions were fabricated for the Schwickerath 3PB and 4PB tests. Strength values were determined from crack initiation while strain energy release rate values were determined from the minima in the force-displacement curves with the 3PB test (Schneider and Swain, 2015) [3] and for 4PB test from the plateau region of stable crack extension. RESULTS: Strength values for the resin and glass bonded glass ceramics to zirconia were 22.20±6.72MPa and 27.02±3.49MPa respectively. The strain energy release rates for the two methods used were very similar and for the glass bonding, (4PB) 15.14±5.06N/m (or J/m2) and (3PB) 16.83±3.91N/m and resin bonding (4PB) 8.34±1.93N/m and (3PB) 8.44±2.81N/m respectively. The differences in strength and strain energy release rate for the two bonding approaches were statistically significant (p<0.05). SEM observations showed fracture occurred adhesively for the resin bonding and cohesively for the glass bonding. SIGNIFICANCE: The present results indicate 3PB and 4PB tests have very similar values for the strain energy release rate determination. However while strength tests reveal minimal differences between resin and glass bonding, strain energy release rates for the latter are superior for bonding CAD/CAM milled glass-ceramics to zirconia.