On-chip bioorthogonal chemistry enables immobilization of in situ modified nanoparticles and small molecules for label-free monitoring of protein binding and reaction kinetics.

Efficient methods to immobilize small molecules under continuous-flow microfluidic conditions would greatly improve label-free molecular interaction studies using biosensor technology. At present, small-molecule immobilization chemistries require special conditions and in many cases must be performed outside the detector and microfluidic system where real-time monitoring is not possible. Here, we have developed and optimized a method for on-chip bioorthogonal chemistry that enables rapid, reversible immobilization of small molecules with control over orientation and immobilization density, and apply this technique to surface plasmon resonance (SPR) studies. Immobilized small molecules reverse the orientation of canonical SPR interaction studies, and also enable a variety of new SPR applications including on-chip assembly and interaction studies of multicomponent structures, such as functionalized nanoparticles, and measurement of bioorthogonal reaction rates. We use this approach to demonstrate that on-chip assembled functionalized nanoparticles show a preserved ability to interact with their target protein, and to measure rapid bioorthogonal reaction rates with k(2) > 10(3) M(-1) s(-1). This method offers multiple benefits for microfluidic biological applications, including rapid screening of targeted nanoparticles with vastly decreased nanoparticle synthetic requirements, robust immobilization chemistry in the presence of serum, and a continuous flow technique that mimics biologic contexts better than current methods used to measure bioorthogonal reaction kinetics such as NMR or UV-vis spectroscopy (e.g., stopped flow kinetics). Taken together, this approach constitutes a flexible and powerful technique for evaluating a wide variety of reactions and intermolecular interactions for in vitro or in vivo applications.

Canine hip dysplasia is predictable by genotyping.

OBJECTIVE: To establish a predictive method using whole genome genotyping for early intervention in canine hip dysplasia (CHD) risk management, for the prevention of the progression of secondary osteoarthritis (OA), and for selective breeding. DESIGN: Two sets of dogs (six breeds) were genotyped with dense SNPs covering the entire canine genome. The first set contained 359 dogs upon which a predictive formula for genomic breeding value (GBV) was derived by using their estimated breeding value (EBV) of the Norberg angle (a measure of CHD) and their genotypes. To investigate how well the formula would work for an individual dog with genotype only (without using EBV), a cross validation was performed by masking the EBV of one dog at a time. The genomic data and the EBV of the remaining dogs were used to predict the GBV for the single dog that was left out. The second set of dogs included 38 new Labrador retriever dogs, which had no pedigree relationship to the dogs in the first set. RESULTS: The cross validation showed a strong correlation (R>0.7) between the EBV and the GBV. The independent validation showed a moderate correlation (R=0.5) between GBV for the Norberg angle and the observed Norberg angle (no EBV was available for the new 38 dogs). Sensitivity, specificity, positive and negative predictive values of the genomic data were all above 70%. CONCLUSIONS: Prediction of CHD from genomic data is feasible, and can be applied for risk management of CHD and early selection for genetic improvement to reduce the prevalence of CHD in breeding programs. The prediction can be implemented before maturity, at which age current radiographic screening programs are traditionally applied, and as soon as DNA is available.

Is the Royal London Space Analysis reliable and does it influence orthodontic treatment decisions?

The purpose of this study was to investigate the reliability of the Royal London Space Analysis (RLSA) and to evaluate its influence on orthodontic treatment decisions. Thirty-one case records were collected to represent various levels of crowding and different types of malocclusions. Seventeen examiners assessed these records and completed a data sheet that recorded information on their treatment decision. One month later, the examiners attended a course on the RLSA and then used the analysis to rescore the 31 cases. The models were also scored by the expert who led the course and these were then considered the 'gold standard' scores. After a further month, the examiners reapplied the RLSA and formulated a treatment plan for each set of patient records. A paired Student's t-test and intraclass correlation coefficient (ICC) were used to assess the agreement in scoring RLSA, a paired sample t-test was used to compare the scores with the gold standard, and finally the reliability in treatment planning was determined using kappa (kappa) statistics. The scores for lower arch crowding showed the highest inter-examiner agreement with an ICC of 0.93 whereas the lowest level of agreement was for upper arch space requirement with an ICC of 0.77. Intra-examiner agreement was generally high, particularly for the assessment of lower arch crowding (ICC = 0.93) and lower arch space requirement (ICC = 0.88). There was excellent validity for all the examiners against the gold standard scores with a paired samples correlation ranging between 0.96 for lower arch crowding and 0.79 for upper arch space requirement. The intra-examiner reliability in treatment decision was only moderate, with an average kappa value of 0.52 (maximum 0.82, minimum 0.24). Intra- and inter-examiner agreement for scoring the RLSA was acceptable. Nevertheless, the additional information obtained from the application of the RLSA did not have a substantial impact on the treatment decisions.

Distributions of high-density lipoprotein particle components in human follicular fluid and sera and their associations with embryo morphology parameters during IVF.

BACKGROUND: High-density lipoprotein (HDL) is the sole lipoprotein present in follicular fluid (FF). The objectives of this study were to examine HDL lipid composition and associated enzyme activities in FF and serum and to relate these levels to embryo morphology parameters in women undergoing in vitro fertilization (IVF). METHODS: Serum and FF were prospectively obtained from 60 women undergoing IVF. HDL lipids, apolipoprotein AI (ApoAI), paraoxonase 1 (PON1) and paraoxonase 3 (PON3) activities were determined. Bivariate analysis and ordinal logistic regression models were employed to examine the associations between biochemical measures and embryo morphology parameters [embryo cell number (ECN) and embryo fragmentation score (EFS)] as surrogate markers of oocyte health. RESULTS: All biochemical parameters were significantly (P < 0.05) lower in FF than serum except PON3 levels which were significantly higher. FF-HDL cholesterol (OR 0.66, 95%CI 0.46-0.96) and ApoAI (OR 0.13, 95%CI 0.03-0.97) levels were negative predictors for EFS; however, their effects were not independent and the level of one moderated the effect of the other. Limited to Day 3 embryo transfers, FF-PON1-arylesterase activity was a significant positive predictor for ECN (OR 1.09, 95%CI 1.01-1.17). CONCLUSIONS: In this pilot study, our data suggests that HDL and its component proteins within FF may play protective roles in the health of the human oocyte and subsequent early embryo development. We describe for the first time the activities of PON1 and PON3 in FF. We suspect that PON3 activity may be locally generated due to higher activities in FF compared with serum.

Which orthodontic archwire sequence? A randomized clinical trial.

The aim of this study was to compare three orthodontic archwire sequences. One hundred and fifty-four 10- to 17-year-old patients were treated in three centres and randomly allocated to one of three groups: A = 0.016-inch nickel titanium (NiTi), 0.018 x 0.025-inch NiTi, and 0.019 x 0.025-inch stainless steel (SS); B = 0.016-inch NiTi, 0.016-inch SS, 0.020-inch SS, and 0.019 x 0.025-inch SS; and C = 0.016 x 0.022-inch copper (Cu) NiTi, 0.019 x 0.025-inch CuNiTi, and 0.019 x 0.025-inch SS. At each archwire change and for each arch, the patients completed discomfort scores on a seven-point Likert scale at 4 hours, 24 hours, 3 days, and 1 week. Time in days and the number of visits taken to reach a 0.019 x 0.025-inch SS working archwires were calculated. A periapical radiograph of the upper left central incisor was taken at the start of the treatment and after placement of the 0.019 x 0.025-inch SS wire so root resorption could be assessed. There were no statistically significant differences between archwire sequences A, B, or C for patient discomfort (P > 0.05) or root resorption (P = 0.58). The number of visits required to reach the working archwire was greater for sequence B than for A (P = 0.012) but this could not be explained by the increased number of archwires used in sequence B.

The "Chesterfield stent": an aid to the placement of midpalatal implants.

A palatal endosseous implant is a valuable adjunct to orthodontic treatment. Its insertion is considerably simplified by the use of a stent that was designed in our department and that we describe here.

A comparison of current Orthodontic Board examinations.

Five orthodontic clinical Board examinations were systematically compared. An attempt was made to critically evaluate the procedures, characteristics and requirements of these examinations. Many similarities were found and the differences found between Boards may be due to differences in socio-political goals of the professional orthodontic societies organizing the examinations. By setting a high standard of clinical treatment as a basic goal, all Boards aim to raise the overall quality of clinical performance.

Orthodontic palatal implants: clinical technique.

The aim of this paper is to familiarize the readers with some of the clinical considerations necessary to ensure successful use of mid-palatal implants. Both surgical and technical aspects will be discussed along with a description of impression techniques used.

Neurobehavioral assessment: a survey of use and value in safety assessment studies.

This report describes the results of a survey designed to evaluate the contribution of F1 neurobehavioral testing to hazard identification and characterization in safety assessment studies. (To review the details of the distributed survey, please see the supplementary data for this article on the journal's Web site.) The survey provided information about studies completed in industrial laboratories in the United States, Europe, and Japan since 1990 on 174 compounds. The types of compounds included were pharmaceutical (81%), agricultural (7%), industrial (1%), or were undefined (10%). Information collected included the intended use of the test agent, general study design and methodology, the types and characteristics of F1 behavioral evaluations, and the frequency with which agents affected neurobehavioral parameters in comparison to other F0 and F1 generation parameters. F1 general toxicology parameters such as mortality, pre- and postweaning body weight, and food intake were assessed in most studies and were affected more frequently than other parameters by the test agents. F1 behavioral parameters were assessed less consistently across studies, and were less frequently affected by the agents tested. Although affected by agents less often than general toxicology parameters, F1 behavioral parameters along with other parameters defined the no-observed-effect level (NOEL) in 17/113 (15%) of studies and solely defined the NOEL in 3/113 (2.6%) of studies. Thus, F1 behavioral parameters sometimes improved on the standard toxicological measures of hazard identification. While not detecting agent effects as readily as some measures, the F1 behavioral parameters provide information about agent effects on specialized functions of developing offspring not provided by other standard measures of toxicity. The survey results emphasize the need for further research into the methods of behavioral assessment as well as the mechanisms underlying the neurobehavioral alterations.

Manipulation of digital photographs.

This article provides simple details of what to do with digital images once they have been captured. Inspection of the images as 'thumbnails' using Exif viewer is described, as well as zooming in to check detail contained on the images. Storage of every orthodontic patient using the popular programme, Dentofacial Showcase is described in some detail. For more formal verbal presentations or written material intended for display Microsoft Powerpoint is the programme of choice. Transfer of the images between the three programmes is described in detail, as well as recommended layouts for written and verbal presentations.

Clinical photographs--the gold standard.

This survey was carried out to allow a minimum data set required for intra- and extra-oral photographs to be established. In 1999 a questionnaire was sent to members of the Angle Society of Europe to establish their current clinical practice with regard to extra- and intra-oral photography. The Angle Society was chosen because of their stated commitment to a high standard of record keeping and of clinical care. Results showed that a full series of extra- and intra-oral photographs were taken both before and after treatment, as well as stage photographs during treatment on many cases. The need for each of these photographs will be discussed in some detail, and recommendations will be made as to what would be considered the Gold standard before, during, and after a course of orthodontic treatment.

Task force report: future research needs for the prevention and management of immune-mediated drug hypersensitivity reactions.

Immune-mediated drug hypersensitivity reactions (IDHR) have a significant impact on clinical practice, drug development, and public health. However, research to understand IDHR mechanisms and to develop diagnostic and predictive tests has been limited. To stimulate more research, a task force with representatives from the key stakeholders (research clinicians, regulatory scientists, and immunotoxicologists from the pharmaceutical industry) was assembled to identify critical data gaps and opportunities and to make recommendations on how to overcome some of the barriers to IDHR research and address research needs. It is hoped that this report will act as a springboard for future discussions and progress toward increased funding and development of organizational structures for IDHR research.

Orthodontic treatment of patients with medical disorders.

This article will highlight some of the problems encountered when orthodontic treatment is provided for patients who have serious medical conditions. The way in which various disease processes might influence treatment decisions will be described, as well as recommended methods of avoiding potential problems.

Digital photography in orthodontics.

A brief history of digital photography is provided along with a critical appraisal of the 'prosumer' and professional systems currently available. Recommendations are made as to the system best suited to current orthodontic practice.

Comparative analysis of the expression patterns of Wnts and Frizzleds during early myogenesis in chick embryos.

During embryogenesis, the transduction of Wnt signals through Frizzled receptors is thought to play integral roles in myogenesis and somite patterning. However, little is known about which Wnt-Frizzled interactions are required for skeletal myogenesis. Thus, we sought to determine which Wnts and Frizzled exhibit expression patterns that are spatiotemporally consistent with the expression of two myogenic determination factors: Myf-5 and MyoD. To accomplish this, we first isolated partial cDNAs for six chick Frizzled orthologues and then compared the expression patterns of chick Frizzleds and Wnts to myogenic and somite patterning factors, such as Myf-5, MyoD, Sonic Hedgehog (Shh), Pax-1 and Pax-3 in Hamburger and Hamilton stage 10 chick. We used these data to generate a schematic composite of expression patterns at the level of the segmental plate and developing somites (stage V) that shows multiple Frizzled and Wnt transcripts expressed in tissues that are overlapping and adjacent to Myf-5 and MyoD expressing tissues.

Digital records in orthodontics.

In this electronic age there is a general move to digital records. In orthodontics this includes digital photography, digital radiography and the latest development, digital study models. The advantages and occasional disadvantages of this digital technology will be discussed in some detail.