Monitoring thrombin generation by electrochemistry: development of an amperometric biosensor screening test for plasma and whole blood

BACKGROUND: Complete investigation of thrombophilic or hemorrhagic clinical presentations is a time-, apparatus-, and cost-intensive process. Sensitive screening tests for characterizing the overall function of the hemostatic system, or defined parts of it, would be very useful. For this purpose, we are developing an electrochemical biosensor system that allows measurement of thrombin generation in whole blood as well as in plasma. METHODS: The measuring system consists of a single-use electrochemical sensor in the shape of a strip and a measuring unit connected to a personal computer, recording the electrical signal. Blood is added to a specific reagent mixture immobilized in dry form on the strip, including a coagulation activator (e.g., tissue factor or silica) and an electrogenic substrate specific to thrombin. RESULTS: Increasing thrombin concentrations gave standard curves with progressively increasing maximal current and decreasing time to reach the peak. Because the measurement was unaffected by color or turbidity, any type of blood sample could be analyzed: platelet-poor plasma, platelet-rich plasma, and whole blood. The test strips with the predried reagents were stable when stored for several months before testing. Analysis of the combined results obtained with different activators allowed discrimination between defects of the extrinsic, intrinsic, and common coagulation pathways. Activated protein C (APC) predried on the strips allowed identification of APC-resistance in plasma and whole blood samples. CONCLUSIONS: The biosensor system provides a new method for assessing thrombin generation in plasma or whole blood samples as small as 10 microL. The assay is easy to use, thus allowing it to be performed in a point-of-care setting.

A treatment method for Class II Division 1 patients with extraction of permanent maxillary first molars

Throughout the years, various treatment modalities have been presented for the treatment of Class II Division 1 malocclusions. The goal of this paper is to present a treatment approach that involves the extraction of the maxillary first molars followed by use of fixed appliances with low-friction brackets. This treatment approach has proven to be an efficient treatment modality for Class II Division 1 malocclusions, especially with noncompliant patients.

Inflammation induces hemorrhage in thrombocytopenia

The role of platelets in hemostasis is to produce a plug to arrest bleeding. During thrombocytopenia, spontaneous bleeding is seen in some patients but not in others; the reason for this is unknown. Here, we subjected thrombocytopenic mice to models of dermatitis, stroke, and lung inflammation. The mice showed massive hemorrhage that was limited to the area of inflammation and was not observed in uninflamed thrombocytopenic mice. Endotoxin-induced lung inflammation during thrombocytopenia triggered substantial intra-alveolar hemorrhage leading to profound anemia and respiratory distress. By imaging the cutaneous Arthus reaction through a skin window, we observed in real time the loss of vascular integrity and the kinetics of skin hemorrhage in thrombocytopenic mice. Bleeding-observed mostly from venules-occurred as early as 20 minutes after challenge, pointing to a continuous need for platelets to maintain vascular integrity in inflamed microcirculation. Inflammatory hemorrhage was not seen in genetically engineered mice lacking major platelet adhesion receptors or their activators (alphaIIbbeta3, glycoprotein Ibalpha [GPIbalpha], GPVI, and calcium and diacylglycerol-regulated guanine nucleotide exchange factor I [CalDAG-GEFI]), thus indicating that firm platelet adhesion was not necessary for their supporting role. While platelets were previously shown to promote endothelial activation and recruitment of inflammatory cells, they also appear indispensable to maintain vascular integrity in inflamed tissue. Based on our observations, we propose that inflammation may cause life-threatening hemorrhage during thrombocytopenia.

Exploiting OSGi capabilities from MHP applications

In this paper we introduce a cooperative environment between the Interactive Digital TV (IDTV) and home networking with the aim of allowing the interaction between interactive TV applications and the controllers of the in-home appliances in a natural way. More specifically, our proposal consists of merging MHP (Multimedia Home Platform), one of the main standard frameworks for IDTV, with OSGi (Open Service Gateway Initiative), the most widely used open platform to set up Residential Gateways. To overcome the radically different nature of these specifications the function-oriented MHP middleware and the service-oriented OSGi framework , we define a new kind of application, coined as XbundLET. Although this software bridge is suitable to enable the interaction between MHP and OSGi applications in both directions, we concretely focus on exposing our implementation experience in only one direction: from MHP to the OSGi world.

Simulative study of the decentralized control of complex conveyor networks

Decentralised controls offer advantages for the implementation as well as the operation of controls of steady conveyors. Such concepts are mainly based on RFID. Due to the reduced expense for appliances and software, however, the plant behaviour cannot be determined as accurately as in centrally controlled systems. This article describes a simulation-based method by which the performances of these two control concepts can easily be evaluated in order to determine the suitability of the decentralised concept.

Matching form with content

Successful computer-supported distance education requires that its enabling technologies are accessible and usable anywhere. They should work seamlessly inside and outside the information superhighway, wherever the target learners are located, without obtruding on the learning activity. It has long been recognised that the usability of interactive computer systems is inversely related to the visibility of the implementing technologies. Reducing the visibility of technology is especially challenging in the area of online language learning systems, which require high levels of interactivity and communication along multiple dimensions such as speaking, listening, reading and writing. In this article, the authors review the concept of invisibility as it applies to the design of interactive technologies and appliances. They describe a specialised appliance matched to the requirements for distance second language learning, and report on a successful multi-phase evaluation process, including initial field testing at a Thai open university.

Matching form with content

Successful computer-supported distance education requires that its enabling technologies are accessible and usable anywhere. They should work seamlessly inside and outside the information superhighway, wherever the target learners are located, without obtruding on the learning activity. It has long been recognised that the usability of interactive computer systems is inversely related to the visibility of the implementing technologies. Reducing the visibility of technology is especially challenging in the area of online language learning systems, which require high levels of interactivity and communication along multiple dimensions such as speaking, listening, reading and writing. In this article, the authors review the concept of invisibility as it applies to the design of interactive technologies and appliances. They describe a specialised appliance matched to the requirements for distance second language learning, and report on a successful multi-phase evaluation process, including initial field testing at a Thai open university.

Survival of palatal miniscrews used for orthodontic appliance anchorage: a retrospective cohort study

INTRODUCTION The purpose of this study was to examine the overall success of miniscrews inserted in the paramedian palatal region for support of various appliances during orthodontic treatment. METHODS The patients received 1 or 2 miniscrews in the paramedian anterior palate of 8.0-mm length and 1.6-mm diameter placed during orthodontic treatment by the same experienced orthodontist. RESULTS In total, 196 patients (121 girls, 75 boys; median age, 11.7; interquartile range, 3.7) who received 384 miniscrews were evaluated. Two hundred four miniscrews were used with rapid palatal expansion appliances, 136 with appliances for distalization of posterior teeth, and 44 with other appliances, such as transpalatal arches for tooth stabilization. The overall survival of the miniscrews was excellent (97.9%) in the cases examined. Cox regression analysis showed no difference in the overall survival rates of miniscrews loaded with different appliances for sex (hazard ratio, 0.95; 95% confidence interval, 0.71-1.27; P = 0.73) after adjusting for appliance and age. CONCLUSIONS This study shows that miniscrews placed in the paramedian anterior palate for supporting various orthodontic appliances have excellent survival.

Curing lights for orthodontic bonding: a systematic review and meta-analysis

INTRODUCTION Light cure of resin-based adhesives is the mainstay of orthodontic bonding. In recent years, alternatives to conventional halogen lights offering reduced curing time and the potential for lower attachment failure rates have emerged. The relative merits of curing lights in current use, including halogen-based lamps, light-emitting diodes (LEDs), and plasma arc lights, have not been analyzed systematically. In this study, we reviewed randomized controlled trials and controlled clinical trials to assess the risks of attachment failure and bonding time in orthodontic patients in whom brackets were cured with halogen lights, LEDs, or plasma arc systems. METHODS Multiple electronic database searches were undertaken, including MEDLINE, EMBASE, and the Cochrane Oral Health Group's Trials Register, CENTRAL. Language restrictions were not applied. Unpublished literature was searched on ClinicalTrials.gov, the National Research Register, Pro-Quest Dissertation Abstracts, and Thesis database. Search terms included randomized controlled trial, controlled clinical trial, random allocation, double blind method, single blind method, orthodontics, LED, halogen, bond, and bracket. Authors of primary studies were contacted as required, and reference lists of the included studies were screened. RESULTS Randomized controlled trials and clinical controlled trials directly comparing conventional halogen lights, LEDs, or plasma arc systems involving patients with full arch, fixed, or bonded orthodontic appliances (not banded) with follow-up periods of a minimum of 6 months were included. Using predefined forms, 2 authors undertook independent extraction of articles; disagreements were resolved by discussion. The assessment of the risk of bias of the randomized controlled trials was based on the Cochrane Risk of Bias tool. Ten studies met the inclusion criteria; 2 were excluded because of high risk of bias. In the comparison of bond failure risk with halogen lights and plasma arc lights, 1851 brackets were included in both groups. Little statistical heterogeneity was observed in this analysis (I(2) = 4.8%; P = 0.379). There was no statistical difference in bond failure risk between the groups (OR, 0.92; 95% CI, 0.68-1.23; prediction intervals, 0.54, 1.56). Similarly, no statistical difference in bond failure risk was observed in the meta-analysis comparing halogen lights and LEDs (OR, 0.96; 95% CI, 0.64-1.44; prediction intervals, 0.07, 13.32). The pooled estimates from both comparisons were OR, 0.93; 95% CI, 0.74-1.17; and prediction intervals, 0.69, 1.17. CONCLUSIONS There is no evidence to support the use of 1 light cure type over another based on risk of attachment failure.

Maxillary sinus floor extension and posterior tooth inclination in adolescent patients with Class II Division 1 malocclusion treated with maxillary first molar extractions

INTRODUCTION Our objective was to investigate potential associations between maxillary sinus floor extension and inclination of maxillary second premolars and second molars in patients with Class II Division 1 malocclusion whose orthodontic treatment included maxillary first molar extractions. METHODS The records of 37 patients (18 boys, 19 girls; mean age, 13.2 years; SD, 1.62 years) treated between 1998 and 2004 by 1 orthodontist with full Begg appliances were used in this study. Inclusion criteria were white patients with Class II Division 1 malocclusion, sagittal overjet of ≥4 mm, treatment plan including extraction of the maxillary first permanent molars, no missing teeth, and no agenesis. Maxillary posterior tooth inclination and lower maxillary sinus area in relation to the palatal plane were measured on lateral cephalograms at 3 time points: at the start and end of treatment, and on average 2.5 years posttreatment. Data were analyzed for the second premolar and second molar inclinations by using mixed linear models. RESULTS The analysis showed that the second molar inclination angle decreased by 7° after orthodontic treatment, compared with pretreatment values, and by 11.5° at the latest follow-up, compared with pretreatment. There was evidence that maxillary sinus volume was negatively correlated with second molar inclination angle; the greater the volume, the smaller the inclination angle. For premolars, inclination increased by 15.4° after orthodontic treatment compared with pretreatment, and by 8.1° at the latest follow-up compared with baseline. The volume of the maxillary sinus was not associated with premolar inclination. CONCLUSIONS We found evidence of an association between maxillary second molar inclination and surface area of the lower sinus in patients treated with maxillary first molar extractions. Clinicians who undertake such an extraction scheme in Class II patients should be aware of this potential association and consider appropriate biomechanics to control root uprighting.

Randomised in situ study on the efficacy of a tin/chitosan toothpaste on erosive-abrasive enamel loss

Tin is a notable anti-erosive agent, and the biopolymer chitosan has also shown demineralisation-inhibiting properties. Therefore, the anti-erosive/anti-abrasive efficacy of the combination of both compounds was tested under in situ conditions. Twenty-seven volunteers were included in a randomised, double-blind, three-cell crossover in situ trial. Enamel specimens were recessed on the buccal aspects of mandibular appliances, extraorally demineralised (6 × 2 min/day) and intraorally treated with toothpaste slurries (2 × 2 min/day). Within the slurry treatment time, one-half of the specimens received additional intraoral brushing (5 s, 2.5 N). The tested toothpastes included a placebo toothpaste, an experimental NaF toothpaste (1,400 ppm F(-)) and an experimental F/Sn/chitosan toothpaste (1,400 ppm F(-), 3,500 ppm Sn(2+), 0.5% chitosan). The percentage reduction of tissue loss (slurry exposure/slurry exposure + brushing) compared to placebo was 19.0 ± 47.3/21.3 ± 22.4 after use of NaF and 52.5 ± 30.9/50.2 ± 34.3 after use of F/Sn/chitosan. F/Sn/chitosan was significantly more effective than NaF (p ≤ 0.001) and showed good efficacy against erosive and erosive-abrasive tissue loss. This study suggests that the F/Sn/chitosan toothpaste could provide good protection for patients who frequently consume acidic foodstuffs.

Effect of a chitosan additive to a Sn(2+)-containing toothpaste on its anti-erosive/anti-abrasive efficacy-a controlled randomised in situ trial

OBJECTIVES It is well known that Sn(2+) is a notable anti-erosive agent. There are indications that biopolymers such as chitosan can enhance the effect of Sn(2+), at least in vitro. However, little information exists about their anti-erosive/anti-abrasive in situ effects. In the present in situ study, the efficacy of Sn(2+)-containing toothpastes in the presence or absence of chitosan was tested. METHODS Ten subjects participated in the randomised crossover study, wearing mandibular appliances with human enamel specimens. Specimens were extraorally demineralised (7 days, 0.5 % citric acid, pH 2.6; 6 × 2 min/day) and intraorally exposed to toothpaste suspensions (2 × 2 min/day). Within the suspension immersion time, one half of the specimens were additionally brushed intraorally with a powered toothbrush (5 s, 2.5 N). Tested preparations were a placebo toothpaste (negative control), two experimental toothpastes (F/Sn = 1,400 ppm F(-), 3,500 ppm Sn(2+); F/Sn/chitosan = 1,400 ppm F(-), 3,500 ppm Sn(2+), 0.5 % chitosan) and an SnF2-containing gel (positive control, GelKam = 3,000 ppm Sn(2+), 1,000 ppm F(-)). Substance loss was quantified profilometrically (μm). RESULTS In the placebo group, tissue loss was 11.2 ± 4.6 (immersion in suspension) and 17.7 ± 4.7 (immersion in suspension + brushing). Immersion in each Sn(2+)-containing suspension significantly reduced tissue loss (p ≤ 0.01); after immersion in suspension + brushing, only the treatments with GelKam (5.4 ± 5.5) and with F/Sn/chitosan (9.6 ± 5.6) significantly reduced loss [both p ≤ 0.05 compared to placebo; F/Sn 12.8 ± 6.4 (not significant)] CONCLUSION Chitosan enhanced the efficacy of the Sn(2+)-containing toothpaste as an anti-erosive/anti-abrasive agent. CLINICAL RELEVANCE The use of Sn(2+)- and chitosan-containing toothpaste is a good option for symptomatic therapy in patients with regular acid impacts.

The SLC1 high-affinity glutamate and neutral amino acid transporter family

Glutamate transporters play important roles in the termination of excitatory neurotransmission and in providing cells throughout the body with glutamate for metabolic purposes. The high-affinity glutamate transporters EAAC1 (SLC1A1), GLT1 (SLC1A2), GLAST (SLC1A3), EAAT4 (SLC1A6), and EAAT5 (SLC1A7) mediate the cellular uptake of glutamate by the co-transport of three sodium ions (Na(+)) and one proton (H(+)), with the counter-transport of one potassium ion (K(+)). Thereby, they protect the CNS from glutamate-induced neurotoxicity. Loss of function of glutamate transporters has been implicated in the pathogenesis of several diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. In addition, glutamate transporters play a role in glutamate excitotoxicity following an ischemic stroke, due to reversed glutamate transport. Besides glutamate transporters, the SLC1 family encompasses two transporters of neutral amino acids, ASCT1 (SLC1A4) and ASCT2 (SLC1A5). Both transporters facilitate electroneutral exchange of amino acids in neurons and/or cells of the peripheral tissues. Some years ago, a high resolution structure of an archaeal homologue of the SLC1 family was determined, followed by the elucidation of its structure in the presence of the substrate aspartate and the inhibitor d,l-threo-benzyloxy aspartate (d,l-TBOA). Historically, the first few known inhibitors of SLC1 transporters were based on constrained glutamate analogs which were active in the high micromolar range but often also showed off-target activity at glutamate receptors. Further development led to the discovery of l-threo-β-hydroxyaspartate derivatives, some of which effectively inhibited SLC1 transporters at nanomolar concentrations. More recently, small molecule inhibitors have been identified whose structures are not based on amino acids. Activators of SLC1 family members have also been discovered but there are only a few examples known.

Lack of Host Gut Microbiota Alters Immune Responses and Intestinal Granuloma Formation during Schistosomiasis

Fatalities from schistosome infections arise due to granulomatous, immune-mediated responses to eggs that become trapped in host tissues. Schistosome-specific immune responses are characterized by initial Th1 responses and our previous studies demonstrated that Myd88-deficient mice failed to initiate such responses in vivo. Paradoxically, schistosomal antigens fail to stimulate innate cells to release pro-inflammatory cytokines in vitro. Since S. mansoni infection is an intestinal disease, we hypothesized that commensal bacteria could act as bystander activators of the intestinal innate immune system to instigate Th1 responses. Using a broad spectrum of orally-administered antibiotics and antimycotics we analyzed schistosome-infected mice that were simultaneously depleted of gut bacteria. After depletion there was significantly less inflammation in the intestine which was accompanied by decreased intestinal granuloma development. In contrast, liver pathology remained unaltered. In addition, schistosome-specific immune responses were skewed and fecal egg excretion was diminished. This study demonstrates that host microbiota can act as a third partner in instigating helminth-specific immune responses.

Comparative efficacy of 2 topical anesthetics for the placement of orthodontic temporary anchorage devices.

This study compared the effectiveness of topical benzocaine 20% versus a combination of lidocaine, tetracaine, and phenylephrine in providing sufficient analgesia for the placement of orthodontic temporary anchorage devices (TADs). The 2 topical anesthetics were tested against each other bilaterally using a randomized, double-blind, crossover design. The agents were left in place for the amount of time prescribed by the manufacturer. The TAD was then placed, and each subject rated the degree of pain on a Heft-Parker visual analogue scale. A pulse oximeter was used to record the preoperative and postoperative pulse rates. Statistically significant differences in perceived pain (P < .05) and success rate (P < .01) between drugs were seen, but no significant difference in pulse rate change between the topical anesthetics was observed (P > .05). It was concluded that when the efficacy of topical benzocaine and of a combination product was compared as the sole anesthetic to facilitate acceptable pain control for placement of orthodontic temporary anchorage devices, the combination product was considerably more efficacious.