Synthesis of Polyanionic C5-Modified 2'-Deoxyuridine and 2'-Deoxycytidine-5'-Triphosphates and Their Properties as Substrates for DNA Polymerases.

Modified 2'-deoxyribonucleotide triphosphates (dNTPs) have widespread applications in both existing and emerging biomolecular technologies. For such applications it is an essential requirement that the modified dNTPs be substrates for DNA polymerases. To date very few examples of C5-modified dNTPs bearing negatively charged functionality have been described, despite the fact that such nucleotides might potentially be valuable in diagnostic applications using Si-nanowire-based detection systems. Herein we have synthesised C5-modified dUTP and dCTP nucleotides each of which are labelled with an dianionic reporter group. The reporter group is tethered to the nucleobase via a polyethylene glycol (PEG)-based linkers of varying length. The substrate properties of these modified dNTPs with a variety of DNA polymerases have been investigated to study the effects of varying the length and mode of attachment of the PEG linker to the nucleobase. In general, nucleotides containing the PEG linker tethered to the nucleobase via an amide rather than an ether linkage proved to be the best substrates, whilst nucleotides containing PEG linkers from PEG6 to PEG24 could all be incorporated by one or more DNA polymerase. The polymerases most able to incorporate these modified nucleotides included Klentaq, Vent(exo-) and therminator, with incorporation by Klenow(exo-) generally being very poor.

A novel method for the accurate evaluation of Poisson's ratio of soft polymer materials.

A new method with a simple algorithm was developed to accurately measure Poisson's ratio of soft materials such as polyvinyl alcohol hydrogel (PVA-H) with a custom experimental apparatus consisting of a tension device, a micro X-Y stage, an optical microscope, and a charge-coupled device camera. In the proposed method, the initial positions of the four vertices of an arbitrarily selected quadrilateral from the sample surface were first measured to generate a 2D 1st-order 4-node quadrilateral element for finite element numerical analysis. Next, minimum and maximum principal strains were calculated from differences between the initial and deformed shapes of the quadrilateral under tension. Finally, Poisson's ratio of PVA-H was determined by the ratio of minimum principal strain to maximum principal strain. This novel method has an advantage in the accurate evaluation of Poisson's ratio despite misalignment between specimens and experimental devices. In this study, Poisson's ratio of PVA-H was 0.44 ± 0.025 (n = 6) for 2.6-47.0% elongations with a tendency to decrease with increasing elongation. The current evaluation method of Poisson's ratio with a simple measurement system can be employed to a real-time automated vision-tracking system which is used to accurately evaluate the material properties of various soft materials.

Tensile and shear mechanical properties of rotator cuff repair patches.

BACKGROUND: Augmentation of rotator cuff tears aims to strengthen the repair and reduce rerupture, yet studies still report high failure rates. This study determines key mechanical properties of rotator cuff repair patches, including establishing values for toughness and measuring the shear properties of repair patches and human rotator cuff tendons. We hypothesized that different repair grafts would (1) have varying material parameters, and (2) not all have mechanical properties similar to human rotator cuff tendons. MATERIALS AND METHODS: Eight specimens each from the Restore, GraftJacket, Zimmer Collagen Repair, and SportsMesh repair patches were tested to failure in tension and for suture pullout. We assessed ultimate tensile strength, tensile (Young's) modulus, and failure strain. This study also established toughness values and shear data. Storage modulus was calculated using dynamic shear analysis for the patches and 18 samples of normal rotator cuff tendon. RESULTS: We report significant variability in important mechanical properties of repair patches, with the mechanical parameters of the patches diverting variously-and often significantly-from values for human rotator cuff tendon. CONCLUSIONS: The repair grafts tested all displayed significant variation in their mechanical properties and had at least some reduced parameters compared with human rotator cuff tendons. This study offers experimentally derived information of value to surgeons when selecting rotator cuff repair grafts. A better understanding of the mechanical suitability of repair grafts for supporting human rotator cuffs is needed if repair patches are to provide a solution for the clinical problem of failure of rotator cuff repairs.

Detection and Stability of SARS-CoV-2 in Three Self-Collected Specimen Types: Flocked Midturbinate Swab (MTS) in Viral Transport Media, Foam MTS, and Saliva.

Respiratory specimen collection materials shortages hampers severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. We compared specimen alternatives and evaluated SARS-CoV-2 RNA stability under simulated shipping conditions. We compared concordance of RT-PCR detection of SARS-CoV-2 from flocked midturbinate swabs (MTS) in viral transport media (VTM), foam MTS without VTM, and saliva. Specimens were collected between August 2020 and April 2021 from three prospective cohorts. We compared RT-PCR cycle quantification (Cq) for Spike (S), Nucleocapsid (N), and the Open Reading Frame 1ab (ORF) genes for flocked MTS and saliva specimens tested before and after exposure to a range of storage temperatures (4-30°C) and times (2, 3, and 7 days). Of 1,900 illnesses with ≥2 specimen types tested, 335 (18%) had SARS-CoV-2 detected in ≥1 specimen; 304 (91%) were concordant across specimen types. Among illnesses with SARS-CoV-2 detection, 97% (95% confidence interval [CI]: 94-98%) were positive on flocked MTS, 99% (95% CI: 97-100%) on saliva, and 89% (95% CI: 84-93%) on foam MTS. SARS-CoV-2 RNA was detected in flocked MTS and saliva stored up to 30°C for 7 days. All specimen types provided highly concordant SARS-CoV-2 results. These findings support a range of viable options for specimen types, collection, and transport methods that may facilitate SARS-CoV-2 testing during supply and personnel shortages. IMPORTANCE Findings from this analysis indicate that (1) self-collection of flocked and foam MTS and saliva samples is feasible in both adults and children, (2) foam MTS with VTM and saliva are both viable and reasonable alternatives to traditional flocked MTS in VTM for SARS-CoV-2 detection, and (3) these sample types may be stored and transported at ambient temperatures for up to 7 days without compromising sample quality. These findings support methods of sample collection for SARS-CoV-2 detection that may facilitate widespread community testing in the setting of supply and personnel shortages during the current pandemic.

Priming with MF59 adjuvanted versus nonadjuvanted seasonal influenza vaccines in children - A systematic review and a meta-analysis.

BACKGROUND: Identifying optimal priming strategies for children <2 years could substantially improve the public health benefits of influenza vaccines. Adjuvanted seasonal influenza vaccines were designed to promote a better immune response among young vaccine-naïve children. METHODS: We systematically reviewed randomized trials to assess hemagglutination inhibition (HAI) antibody response to MF59-adjuvanted inactivated influenza vaccine (aIIV) versus nonadjuvanted IIV among children. We estimated pooled ratios of post-vaccination HAI geometric mean titer (GMT) for aIIV versus IIV and confidence intervals (CIs) using the pooled variances derived from reported CIs. RESULTS: Mean age was 28 months (range, 6-72 months). Children received vaccines with either 7.5 µg (6-35 months) or 15 µg (≥36 months) hemagglutinin of each strain depending on age. Seven of eight trials administered trivalent vaccines and one used quadrivalent vaccine. Pooled post-vaccination GMT ratios against the three influenza vaccine strains were 2.5-3.5 fold higher after 2-dose-aIIV versus 2-dose-IIV among children 6-72 months, and point estimates were higher among children 6-35 months compared with older children. When comparing 1-dose-aIIV to 2-dose-IIV doses, pooled GMT ratios were not significantly different against A/H1N1 (1.0; 95% CI: 0.5-1.8; p = 0.90) and A/H3N2 viruses (1.0; 95% CI: 0.7-1.5; p = 0.81) and were significantly lower against B viruses (0.6; 95% CI: 0.4-0.8; p < 0.001) for both age groups. Notably, GMT ratios for vaccine-mismatched heterologous viruses after 2-dose-aIIV compared with 2-dose-IIV were higher against A/H1N1 (2.0; 95% CI: 1.1-3.4), A/H3N2 (2.9; 95% CI: 1.9-4.2), and B-lineage viruses (2.1; 95% CI: 1.8-2.6). CONCLUSIONS: Two doses of adjuvanted IIV consistently induced better humoral immune responses against Type A and B influenza viruses compared with nonadjuvanted IIVs in young children, particularly among those 6-35 months. One adjuvanted IIV dose had a similar response to two nonadjuvanted IIV doses against Type A influenza viruses. Longer-term benefits from imprinting and cell-mediated immunity, including trials of clinical efficacy, are gaps that warrant investigation.

Mercuric ion sensing by a film bulk acoustic resonator.

This paper describes a film bulk acoustic resonator (FBAR) mass sensor for detecting Hg2+ ion in water with excellent sensitivity and selectivity. When a thin Au film was deposited on the surface of an FBAR, the resonant frequency shifted to a lower value when the film was exposed to Hg2+ in aqueous solution. The FBAR sensor detected as low as 10(-9) M Hg2+ (0.2 ppb Hg2+) in water. Other ions such as K+, Ca2+, Mg2+, Zn2+, and Ni2+ had little or no effect on the resonant frequency of the FBAR. Coating of the FBAR Au surface with a self-assembled monolayer (SAM) of 4-mercaptobenzoic acid decreased the Hg2+ response.

A reversible thermoresponsive sealant for temporary closure of ocular trauma.

Open globe injuries are full-thickness injuries sustained to the eye wall (cornea or sclera), which cause immediate drops in intraocular pressure that may lead to retinal detachment and permanent vision loss if not treated rapidly after injury. The current standard of care for open globe injuries consists of suturing the margins closed, but the technique can be time-consuming, requires specialized training and equipment, and can lead to patient discomfort, abrasion, and infection from eye rubbing. We engineered an injectable, thermoresponsive sealant (TRS) and a custom tool to occlude open globe injuries. The smart hydrogel sealant consists of physically cross-linked N-isopropylacrylamide copolymerized with butylacrylate. At low temperatures, it can be injected as a liquid, and when raised to body temperature, a heat-induced gelation converts the hydrogel into a solidified occlusion. The sealant can be repositioned or removed without causing additional trauma via exposure to cold water. In vitro and ex vivo assessments of mechanical adhesion to eye tissue revealed maintenance of intraocular pressure that is five times greater than the physiological range with reversible seal strength comparable to cyanoacrylate (super glue). In vivo assessment in a rabbit model of ocular trauma demonstrated ease of use for TRS deployment, statistically significant improvement in wound sealing, and no evidence of neurotoxicity, retinal tissue degradation, or significant chronic inflammatory response after 30 days of exposure. Given the advantages of body heat-induced gelation, rapid reversible occlusion, and in vivo safety and efficacy, shape-adaptable TRSs have translational potential as smart wound sealants for temporary occlusion of surgical incisions or traumatic injuries.

Simulation of cell differentiation in fracture healing: mechanically loaded composite scaffolds in a novel bioreactor system.

Cell differentiation during bone healing following a fracture is influenced by various biological and mechanical factors. We introduce a method for the examination of cell and tissue differentiation simulating a fracture gap in vitro. A closed bioreactor system allows the imitation of the biological, mechanical, and biochemical conditions in vitro. The initial hematoma formed in a fracture is simulated with a mixed construct composed of lyophilized cancellous bone and a fibrin matrix in a sandwich configuration. The construct may be loaded with osteoprogenitor cells. Exemplarily, constructs were loaded with rabbit periosteal cells and cultivated under mechanical loading with 7 kPa at 0.05 Hz for up to two weeks. During the observation period, cell morphology and correlating protein synthesis changed under mechanical stimulation. Cell differentiation differed between the various regions of the constructs. The periosteal cells were arranged perpendicularly to the mechanical loading and differentiated to osteoblastic forms with rising collagen type I synthesis, constant alkaline phosphatase activity, and initiation of the calcification of the extracellular matrix. The observed pattern of cell and tissue differentiation was similar to the one seen in the early phase of bone healing. In conclusion, the presented method allows simulation of cell and tissue differentiation during the early phase of fracture healing. It could serve as an in vitro model for the examination of mechanical and pharmacological influences during the early phase of bone healing on a cellular level.

Fracture behavior of inlay and onlay fixed partial dentures - An in-vitro experimental and XFEM modeling study.

OBJECTIVES: This study aimed to explore the "sensitivity" of the fracture load and initiation site to loading position on the central occlusal surface of a pontic tooth for both all-ceramic inlay retained and onlay supported partial denture systems. MATERIALS AND METHODS: Three dimensional (3D) finite element (FE) inlay retained and onlay supported partial denture models were established for simulating crack initiation and propagation by using the eXtended Finite Element Method (XFEM). The models were subjected to a mastication force up to 500N on the central fossa of the pontic. The loading position was varied to investigate its influence on fracture load and crack path. RESULTS: Small perturbation of the loading position caused the fracture load and crack pattern to vary considerably. For the inlay fixed partial dentures (FPDs), the fracture origins changed from the bucco-gingival aspect of the molar embrasure to the premolar embrasure when the indenter force location is slightly shifted from the mesial to distal side. In contrast, for onlay FPDs, cracking initiated from bucco-gingival aspect of the premolar embrasure when the indenter is slightly shifted to the buccal side and from molar embrasure when the indenter is shifted to the lingual side. CONCLUSIONS: The fracture load and cracking path were found to be very sensitive to loading position in the all-ceramic inlay and onlay FPDs. The study provides a basis for improved understanding on the role of localized contact loading of the cusp surface in all-ceramic FPDs.

Sonochemically fabricated microelectrode arrays for biosensors offering widespread applicability: Part I.

A novel and patented procedure is described for the sonochemical fabrication of a new class of microelectrode array based sensor with electrode element populations of up to 2 x 10(5) cm(-2). For some years it has been accepted that microelectrode arrays offer an attractive route for lowering minimum limits of detection and imparting stir (convectional mass transport) independence to sensor responses; despite this no commercial biosensors, to date, have employed microelectrode arrays, largely due to the cost of conventional fabrication routes that have not proved commercially viable for disposable devices. Biosensors formed by our sonochemical approach offer unrivalled sensitivity and impart stir independence to sensor responses. This format lends itself for mass fabrication due to the simplicity and inexpensiveness of the approach; in the first instance impedimetric and amperometric sensors are reported for glucose as model systems. Sensors already developed for ethanol, oxalate and a number of pesticide determinations will be reported in subsequent publications.

Quantitation of poloxamers in pharmaceutical formulations using size exclusion chromatography and colorimetric methods.

Poloxamers have been used as functional excipients in pharmaceutical products. They function as surfactants, emulsifying agents, solubilizing agents, dispersing agents, and in vivo absorbance enhancer. Despite their wide range of applications, limited analytical techniques have been reported in literature for characterizing poloxamers and few are targeted to quantify poloxamer contents in formulations with desired sensitivity and accuracy. In this paper, two distinct analytical methods for quantifying low levels of poloxamers in pharmaceutical formulations have been developed and optimized: a colorimetric method and a size exclusion chromatography method. The colorimetric method is based on the formation of a colored complex between poloxamers and cobalt(II) thiocyanate in aqueous medium, which has a maximum UV absorbance at 624 nm. The feasibility of this method is product specific. In this report, adequate specificity and sensitivity was demonstrated for only one of the several products tested. The size exclusion chromatography (SEC) method utilizes size exclusion columns with THF as mobile phase and refractive index detection. The SEC method provides a limit of quantitation (LOQ) of 0.005 mg/mL (0.0005%, w/w) and at least three orders of magnitudes of linear range. We applied the SEC method to pharmaceutical products containing 0.3-10% poloxamer 188 or poloxamer 407, such as Avapro, Neurontin, Sudafed and other developmental formulations. The results obtained with the SEC method agreed very well with literature and theoretical values with 97-102% recovery. The SEC method was proven to be widely applicable, accurate, precise and simple to use.

Barriers and facilitators to influenza vaccination and vaccine coverage in a cohort of health care personnel.

BACKGROUND: Annual influenza vaccination is recommended for health care personnel (HCP). We describe influenza vaccination coverage among HCP during the 2010-2011 season and present reported facilitators of and barriers to vaccination. METHODS: We enrolled HCP 18 to 65 years of age, working full time, with direct patient contact. Participants completed an Internet-based survey at enrollment and the end of influenza season. In addition to self-reported data, we collected information about the 2010-2011 influenza vaccine from electronic employee health and medical records. RESULTS: Vaccination coverage was 77% (1,307/1,701). Factors associated with higher vaccination coverage include older age, being married or partnered, working as a physician or dentist, prior history of influenza vaccination, more years in patient care, and higher job satisfaction. Personal protection was reported as the most important reason for vaccination followed closely by convenience, protection of patients, and protection of family and friends. Concerns about perceived vaccine safety and effectiveness and low perceived susceptibility to influenza were the most commonly reported barriers to vaccination. About half of the unvaccinated HCP said they would have been vaccinated if required by their employer. CONCLUSION: Influenza vaccination in this cohort was relatively high but still fell short of the recommended target of 90% coverage for HCP. Addressing concerns about vaccine safety and effectiveness are possible areas for future education or intervention to improve coverage among HCP.

A comparative mechanical and bone remodelling study of all-ceramic posterior inlay and onlay fixed partial dentures.

OBJECTIVES: Comparative studies of bone remodelling and mechanical stresses between inlay and onlay fixed partial dentures (FPD) are rather limited. The purpose of this paper was to evaluate the biological consequence in posterior mandibular bone and the mechanical responses in these two different prosthetic configurations. METHODS: Three-dimensional (3D) finite element analysis (FEA) models are created to explore the mechanical responses for the inlay and onlay preparations within the same oral environment. Strain induced bone remodelling was simulated under mastication. The remodelling adopted herein relates the strain in the bone to the change of Hounsfield Unit (HU) value in proportion to the surface area density (SAD) of bony morphology, which allows directly correlating to clinical computerised tomography (CT) data. RESULTS: The results show that both FPD designs exhibit a similar resultant change in bone mineral density (BMD) though the onlay configuration leads to a more uniform distribution of bone density. The inlay design results in higher mechanical stresses whilst allowing preservation of healthy tooth structure. CONCLUSIONS: This study provides an effective means to further clinical assessment and investigation into biomechanical responses and long-term restorative outcome with different FPD designs. CLINICAL SIGNIFICANCE: Quantifying in vivo stress distributions associated with inlay/onlay FPDs can further supplement clinical investigations into prosthetic durability, FPD preparation techniques (i.e., taper angles, material development), consequent stress distributions and the ongoing biomechanical responses of mandibular bone.

Surface chemical immobilization of parylene C with thermosensitive block copolymer brushes based on N-isopropylacrylamide and N-tert-butylacrylamide: synthesis, characterization, and cell adhesion/detachment.

Poly(N-isopropylacrylamide) (pNIPAM), poly(N-tert-butylacrylamide) (pNTBAM), and their copolymer brushes were covalently immobilized onto parylene C (PC) surfaces via surface initiated atom transfer radical polymerization (ATRP). Contact angle measurement between 13 and 40°C showed that the hydrophobicity of the modified PC surfaces was thermally sensitive. Among these samples, PC grafted with pNIPAM (PC-NI), PC grafted with pNTBAM (PC-NT) and PC grafted with copolymer brushes containing pNTBAM and pNIPAM (PC-NT-NI) exhibited the lower critical solution temperature (LCST) at 29, 22, and 24°C, respectively. Cytocompatibility study for the modified surfaces was performed by 5 days human skin fibroblast culture at 37°C. Data showed that only a very small amount of cells adhered on the PC and PC-NI surfaces, while a significantly higher amount of cell adhesion and growth was observed on PC-NT and PC-NT-NI surfaces. Furthermore, cell detachment at the temperatures of 24 and 6°C were studied after the substrates were cultured with cells at 37°C for 24 h. The results showed that the cells on PC-NI formed the aggregations and loosely attached on the substrate after 30-min culture at 24°C, while no significant cell detachment was observed for PC-NT and PC-NT-NI samples at this temperature. By continuing the cell culture for additional 100 min at 6°C for PC-NT and PC-NT-NI, about 10 and 35% of the cells were found detached respectively, and the unattached cells aggregated on the substrate. In comparison, cells cultured on the tissue culture petri dish (TCP) exhibited no quantity and morphology changes at the culture temperatures of 37, 24, and 6°C. This study showed that: (1) immobilization of PC with nonthermal sensitive pNTBAM could provide PC surface thermal sensitive hydrophilicity; (2) the chlorines on the polymer brushes of PC-NT could be used to further initiate the ATRP pNIPAM and form block copolymer brushes; (3) the incorporation of pNTBAM into pNIPAM on PC-NT-NI could change the surface thermal hydrophilicity property, and be further applied to decrease the LCST of the modified PC surface; (4) grafted pNIPAM brushes on PC-NI by ATRP showed very low cell adhesion and proliferation in 5 days fibroblast culture at 37°C, and cell detached at 24°C; (5) the incorporation of pNTBAM into pNIPAM on PC-NT-NI decreased the thermal sensitivity of cell adhesion/detachment, cell detached at 6°C, but the cell adhesion and proliferation were significantly improved at a wide temperature range.

Chemical surface modification of parylene C for enhanced protein immobilization and cell proliferation.

To introduce the adhesion site of proteins and/or cells on parylene C (PC)-coated medical devices that can be used as implantable biosensors or drug delivery capsules, the PC surfaces were initially modified by the Friedel-Crafts acylation reaction to generate active chlorines. These chlorines were then employed to initiate the atom transfer radical polymerization of tert-butyl acrylate (TBA) and form a polymer brush layer of polyTBA on PC; the acrylate groups in the polymer brushes were hydrolyzed to carboxylic acid groups and further activated into succinimidyl ester groups via the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide coupling reaction. The PC surface grafted with polymer brushes and activated by succinimide showed efficient attachment of proteins, including gelatin, contortrostatin (CN) and bovine serum albumin (BSA), all at high density on the PC surface. The CN density on the surface was evaluated for both monolayer and polymer brush-based coatings. Based on fluorescence measurements, the polymer brush gives a 60-fold higher surface protein density than the monolayer-based system. Gelatin was used as a model protein and covalently coated onto the modified PC surface for cell culture study. Substrates with gelatin coating showed a significantly higher cell attachment and proliferation in 7 days cultures as compared to the uncoated substrates. In addition, a conventional photolithography technique was coupled with the surface chemistry to successfully pattern the BSA labeled with fluorescein isothiocyanate on the modified PC surfaces.

Quantification and significance of fluid shear stress field in biaxial cell stretching device.

A widely used commercially available system for the investigation of mechanosensitivity applies a biaxial strain field to cells cultured on a compliant silicone substrate membrane stretched over a central post. As well as intended substrate strain, this device also provides a fluid flow environment for the cultured cells. In order to interpret the relevance of experiments using this device to the in vivo and clinical situation, it is essential to characterise both substrate and fluid environments. While previous work has detailed the substrate strain, the fluid shear stresses, to which bone cells are known to be sensitive, are unknown. Therefore, a fluid structure interaction computational fluid dynamics model was constructed, incorporating a finite element technique capable of capturing the contact between the post and the silicone substrate membrane, to the underside of which the pump control pressure was applied. Flow verification experiments using 10-µm-diameter fluorescent microspheres were carried out. Fluid shear stress increased approximately linearly with radius along the on-post substrate membrane, with peak values located close to the post edge. Changes in stimulation frequency and culture medium viscosity effected proportional changes in the magnitude of the fluid shear stress (peak fluid shear stresses varied in the range 0.09-3.5 Pa), with minor effects on temporal and spatial distribution. Good agreement was obtained between predicted and measured radial flow patterns. These results suggest a reinterpretation of previous data obtained using this device to include the potential for a strong role of fluid shear stress in mechanosensitivity.

Paraneoplastic syndromes in patients with primary oral cancers: a systematic review.

The aim of this study was to review all the paraneoplastic syndromes of primary tumours of the oral cavity. Metastatic tumours of the mouth and primary tumours of the oropharynx (including tonsils), and major salivary glands were excluded. The primary search was conducted on PubMed, Scopus and EMBASE, and included every paraneoplastic syndrome from a primary oral tumour described in English, French, or German papers during the last 20 years. The secondary search was conducted by handpicking articles from reviews on paraneoplastic syndromes of the head and neck. The aim of the tertiary search was to identify conditions that had been reported only rarely. We then cross-referenced "mouth neoplasm" with every paraneoplastic condition cited in relevant review articles. We classified the paraneoplastic syndromes that arose from tumours of the head and neck into six categories: endocrine, dermatological, vascular and haematological, rheumatoid, ocular, and neurological. The following conditions are described in this review: syndrome of inappropriate antidiuretic hormone production, hypercalcaemia, hypercalcaemia-leucocytosis syndrome, ectopic production of beta-human chorionic gonadotrophin, Bazex syndrome, Sweet syndrome, tripe palm syndrome, pemphigus, pityriasis rotunda, neutrophilic leukemoid reaction, cerebral venous sinus thrombophlebitis, digital ischaemia, dermatomyositis, necrotising myopathy, autoimmune retinal degeneration, and subacute cerebellar degeneration. Paraneoplastic syndromes of the oral cavity are a heterogeneous group. Most syndromes occur from squamous cell carcinoma and their aetiology is poorly understood. They are important to recognise as they can be the presenting complaint of a malignant tumour, change the prognosis, and considerably reduce the quality of life.

Prediction of mandibular bone remodelling induced by fixed partial dentures.

Fixed partial dentures (FPD) or dental bridges have been extensively utilised in prosthodontic restoration. Despite considerable clinical success to date, there has been limited fundamental understanding of the biomechanical consequences induced by FPD treatment. It is noted that FPD construction significantly alters the biological and mechanical environment in the supporting bone region. Thus, the surrounding bones will be engaged to adapt to such a biomechanical change. This paper aims to address this critical issue by developing a new remodelling procedure induced by FPD restoration. Specifically, it relates the mechanical stimulus to the change in Hounsfield Unit (HU) value in terms of surface area density (SAD) of bony morphology, which allows direct correlation to clinical computerised tomography (CT) data. The procedure will provide prosthodontist with a new approach for assessing FPD treatment, thereby optimising FPD design for improving longevity and reliability of future FPD restoration.

Combined magnetic resonance and optical imaging of head and neck tumor xenografts using Gadolinium-labelled phosphorescent polymeric nanomicelles.

BACKGROUND: The overall objective of this study was to develop a nanoparticle formulation for dual modality imaging of head and neck cancer. Here, we report the synthesis and characterization of polymeric phospholipid-based nanomicelles encapsulating near-infrared (NIR) phosphorescent molecules of Pt(II)-tetraphenyltetranaphthoporphyrin [Pt(TPNP)] and surface functionalized with gadolinium [Pt(TPNP)-Gd] for combined magnetic resonance imaging (MRI) and NIR optical imaging applications. METHODS: Dynamic light scattering, electron microscopy, optical spectroscopy and MR relaxometric measurements were performed to characterize the optical and magnetic properties of nanoparticles in vitro. Subsequently, in vivo imaging experiments were carried out using nude mice bearing primary patient tumor-derived human head and neck squamous cell carcinoma xenografts. RESULTS: The nanomicelles were ~100 nm in size and stable in aqueous suspension. T1-weighted MRI and relaxation rate (R1 = 1/T1) measurements carried out at 4.7 T revealed enhancement in the tumor immediately post injection with nanomicelles, particularly in the tumor periphery which persisted up to 24 hours post administration. Maximum intensity projections (MIPs) generated from 3D T1-weighted images also demonstrated visible enhancement in contrast within the tumor, liver and blood vessels. NIR optical imaging performed (in vivo and ex vivo) following completion of MRI at the 24 h time point confirmed tumor localization of the nanoparticles. The large spectral separation between the Pt(TPNP) absorption (~700 nm) and phosphorescence emission (~900 nm) provided a dramatic decrease in the level of background, resulting in high contrast optical (NIR phosphorescence) imaging. CONCLUSIONS: In conclusion, Pt(TPNP)-Gd nanomicelles exhibit a high degree of tumor-avidity and favorable imaging properties that allow for combined MR and optical imaging of head and neck tumors. Further investigation into the potential of Pt(TPNP)-Gd nanomicelles for combined imaging and therapy of cancer is currently underway.