[Growth disturbances of the temporomandibular joint: causes, diagnosis and treatment]. / Groeistoornissen van het kaakgewricht: oorzaken, diagnose en behandeling.

Growth disturbances of the temporomandibular Joint are characterized by mandibular asymmetry, sometimes with secondary maxillar disturbances. Although the clinical symptoms are sometimes quite severe, patients usually have no pain. There are several growth disturbances, but in this article we discuss three particular causes of facial asymmetry, namely hemimandibular growth defects; overdevelopment, underdevelopment and neoplasms of the mandibular joint. Hemimandibular overdevelopment (hyperplasia) is a growth disorder characterized by progressive asymmetry of the mandibula. Hemimandibular hypoplasia, on the other hand, is a growth disorder involving underdevelopment of the condyle mandibulae due to impingement of the growth center and ankylosing. A pronounced asymmetrical face can cause aesthetic problems and always requires diagnostics, because in addition to the hyperplasia and hypoplasia mentioned above, other causes can explain the asymmetry such as, for example, an osteoarthritis or even a tumor emanating from the base of the skull, mandibula or soft tissues.

[Internal derangements of the temporomandibular joint]. / Internal derangements van het kaakgewricht.

An internal derangement of the temporomandibular joint is described as a deviation in the position or shape of the joint tissues. Such a change is only functionally manifest if it interferes with smooth movements of the jaw joint. There are a number of internal derangements associated with jaw movements in which popping jaw joint sounds can occur. Examples are an anteriorly or posteriorly displaced disc and hypermobility of the condylar head. Although most internal derangements are harmless and only cause minor discomfort to patients, disc displacements can in some cases develop into a clinical problem, for example when there is a limitation of mouth opening (so-called closed lock) or an inability to close the mouth (so-called open lock). Most patients with these conditions do not require any or only conservative treatment.

High-Q Magnetic Levitation and Control of Superconducting Microspheres at Millikelvin Temperatures.

We report the levitation of a superconducting lead-tin sphere with 100 µm diameter (corresponding to a mass of 5.6 µg) in a static magnetic trap formed by two coils in an anti-Helmholtz configuration, with adjustable resonance frequencies up to 240 Hz. The center-of-mass motion of the sphere is monitored magnetically using a dc superconducting quantum interference device as well as optically and exhibits quality factors of up to 2.6×10^{7}. We also demonstrate 3D magnetic feedback control of the motion of the sphere. The setup is housed in a dilution refrigerator operating at 15 mK. By implementing a cryogenic vibration isolation system, we can attenuate environmental vibrations at 200 Hz by approximately 7 orders of magnitude. The combination of low temperature, large mass, and high quality factor provides a promising platform for testing quantum physics in previously unexplored regimes with high mass and long coherence times.

[Deep Margin Elevations, clinical considerations]. / Deep Margin Elevations in de praktijk.

Subgingival restorations are problematic due to reduced visibility at the preparation margins, humidity (saliva, crevicular fluid and/or blood), problems with taking impressions (digital or analogue) and problems with the application of a rubber dam. Solutions, such as the use of a surgical microscope, retraction cord and Teflon tape, are available. Since modern dentistry largely relies upon adhesive techniques with hydrophobic materials, these require a clean and dry working area. One solution is to place the preparation margin supragingivally. This can be done in three ways: a local build-up using a direct composite restoration, a surgical clinical crown lengthening or an extrusion (orthodontic or surgical). Since in practice only a small part is usually located subgingivally, placing a direct composite restoration is often sufficient. The term Deep Margin Elevation is generally used in the international English-language literature for this approach. If the area located subgingivally is larger, then techniques like crown lengthening and extrusion might be better.

[Surgical extrusion, an alternative to a dental implant?] / Chirurgische extrusie, een alternatief voor een tandheelkundig implantaat?

Unfortunately, accidents do happen. Dentoalveolar injury to the front teeth resulting from trauma can sometimes be so problematic that an (adhesive) restoration seems almost impossible to make, let alone saving the tooth. In this contribution the case of a 17-year-old patient whose upper incisor suffered severe dentoalveolar trauma in a traffic accident is presented. His upper incisor was fractured deeply subgingivally, at bone level, and at first glance, appeared to be lost. Surgical extrusion, however, in this patient represents a full alternative to a prosthetic solution, such as a dental implant.

Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project.

Adequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region-specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch-to-batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.

Challenges in the implementation of EAACI guidelines on allergen immunotherapy: A global perspective on the regulation of allergen products.

Regulatory approaches for allergen immunotherapy (AIT) products and the availability of high-quality AIT products are inherently linked to each other. While allergen products are available in many countries across the globe, their regulation is very heterogeneous. First, we describe the regulatory systems applicable for AIT products in the European Union (EU) and in the United States (US). For Europe, a depiction of the different types of relevant procedures, as well as the committees involved, is provided and the fundamental role of national agencies of the EU member states in this complex and unique network is highlighted. Furthermore, the regulatory agencies from Australia, Canada, Japan, Russia, and Switzerland provided information on the system implemented in their countries for the regulation of allergen products. While AIT products are commonly classified as biological medicinal products, they are made available by varying types of procedures, most commonly either by obtaining a marketing authorization or by being distributed as named patient products. Exemptions from marketing authorizations in exceptional cases, as well as import of allergen products from other countries, are additional tools applied by countries to ensure availability of needed AIT products. Several challenges for AIT products are apparent from this analysis and will require further consideration.

Accurate quantification of 5 German cockroach (GCr) allergens in complex extracts using multiple reaction monitoring mass spectrometry (MRM MS).

BACKGROUND: German cockroach (GCr) allergen extracts are complex and heterogeneous products, and methods to better assess their potency and composition are needed for adequate studies of their safety and efficacy. OBJECTIVE AND METHODS: The objective of this study was to develop an assay based on liquid chromatography and multiple reaction monitoring mass spectrometry (LC-MRM MS) for rapid, accurate, and reproducible quantification of 5 allergens (Bla g 1, Bla g 2, Bla g 3, Bla g 4, and Bla g 5) in crude GCr allergen extracts. RESULTS: We first established a comprehensive peptide library of allergens from various commercial extracts as well as recombinant allergens. Peptide mapping was performed using high-resolution MS, and the peptide library was then used to identify prototypic and quantotypic peptides to proceed with MRM method development. Assay development included a systematic optimization of digestion conditions (buffer, digestion time, and trypsin concentration), chromatographic separation, and MS parameters. Robustness and suitability were assessed following ICH (Q2 [R1]) guidelines. The method is precise (RSD < 10%), linear over a wide range (r > 0.99, 0.01-1384 fmol/µL), and sensitive (LLOD and LLOQ <1 fmol/µL). Having established the parameters for LC-MRM MS, we quantified allergens from various commercial GCr extracts and showed considerable variability that may impact clinical efficacy. CONCLUSIONS AND CLINICAL RELEVANCE: Our data demonstrate that the LC-MRM MS method is valuable for absolute quantification of allergens in GCr extracts and likely has broader applicability to other complex allergen extracts. Definitive quantification provides a new standard for labelling of allergen extracts, which will inform patient care, enable personalized therapy, and enhance the efficacy of immunotherapy for environmental and food allergies.

Cyprinid herpesvirus 3 as a potential biological control agent for carp (Cyprinus carpio) in Australia: susceptibility of non-target species.

Carp (Cyprinus carpio L.) is a pest species in Australian waterways, and cyprinid herpesvirus 3 (CyHV-3) is being considered as a potential biological control (biocontrol) agent. An important consideration for any such agent is its target specificity. In this study, the susceptibility to CyHV-3 of a range of non-target species (NTS) was tested. The NTS were as follows: 13 native Australian, and one introduced, fish species; a lamprey species; a crustacean; two native amphibian species (tadpole and mature stages); two native reptilian species; chickens; and laboratory mice. Animals were exposed to 100-1000 times the approximate minimum amount of CyHV-3 required to cause disease in carp by intraperitoneal and/or bath challenge, and then examined clinically each day over the course of 28 days post-challenge. There were no clinical signs, mortalities or histological evidence consistent with a viral infection in a wide taxonomic range of NTS. Furthermore, there was no molecular evidence of infection with CyHV-3, and, in particular, all RT-PCRs for viral mRNA were negative. As a consequence, the results encourage further investigation of CyHV-3 as a potential biocontrol agent that is specific for carp.

A duplex qPCR for the simultaneous detection of Escherichia coli O157:H7 and Listeria monocytogenes using LNA probes.

UNLABELLED: In this study, a duplex qPCR assay was developed for the needs of the Irish fish industry to screen for the two major food-borne pathogens of fish, Listeria monocytogenes and Escherichia coli O157:H7. The assay can claim positive or negative results for two pathogens in one go in only 20 h including 16 h universal pre-enrichment and compared to traditional ISO approved plate culture methods the labour and the cost involved in testing of one sample is reduced to minimum. The highly specific genomic areas targeted for PCR amplification in the assay are the hly gene for listeriolysin O (LLO) of L. monocytogenes and the stx gene for Shiga-like toxin expressed by E. coli O157:H7. The detection limit of the assay is consistent with the consumer protection limits of 1 pg genomic DNA or 1 CFU 25 g(-1) fish meat (with enrichment) allowing the test to be considered as a substitute to standard plate culture methods. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights a novel duplex qPCR for Listeria monocytogenes and Escherichia coli O157:H7 that could be used as an alternative to plate-based ISO or singleplex PCR methods while minimizing the costs. The assay uses rapid DNA extraction methods and locked nucleic acid probes. Sensitivity and specificity are 100 and 98·95% respectively. The potential for quantitative rage of the assay is 10(8) -10(1) CFU ml(-1) .

Reduction in interval cancer rates following the introduction of two-view mammography in the UK breast screening programme.

BACKGROUND: The introduction of two-view mammography at incident (subsequent) screens in the National Health Service Breast Screening Programme (NHSBSP) has led to an increased number of cancers detected at screen. However, the effect of two-view mammography on interval cancer rates has yet to be assessed. METHODS: Routine screening and interval cancer data were collated from all screening programmes in the United Kingdom for women aged 50-64, screened between 1 April 2003 and 31 March 2005. Interval cancer rates were compared based on whether two-view mammography was in use at the last routine screen. RESULTS: The reduction in interval cancers following screening using two-view mammography compared with one view was 0.68 per 1,000 women screened. Overall, this suggests the introduction of two-view mammography at incident screen was accompanied by a 15-20% reduction in interval cancer rates in the NHSBSP. CONCLUSION: The introduction of two-view mammography at incident screens is associated with a reduction in incidence of interval cancers. This is consistent with previous publications on a contemporaneous increase in screen-detected cancers. The results provide further evidence of the benefit of the use of two-view mammography at incident screens.

Modeling a measurement-device-independent quantum key distribution system.

We present a detailed description of a widely applicable mathematical model for quantum key distribution (QKD) systems implementing the measurement-device-independent (MDI) protocol. The model is tested by comparing its predictions with data taken using a proof-of-principle, time-bin qubit-based QKD system in a secure laboratory environment (i.e. in a setting in which eavesdropping can be excluded). The good agreement between the predictions and the experimental data allows the model to be used to optimize mean photon numbers per attenuated laser pulse, which are used to encode quantum bits. This in turn allows optimization of secret key rates of existing MDI-QKD systems, identification of rate-limiting components, and projection of future performance. In addition, we also performed measurements over deployed fiber, showing that our system's performance is not affected by environment-induced perturbations.

Efficient Bell state analyzer for time-bin qubits with fast-recovery WSi superconducting single photon detectors.

We experimentally demonstrate a high-efficiency Bell state measurement for time-bin qubits that employs two superconducting nanowire single-photon detectors with short dead-times, allowing projections onto two Bell states, |ψ⁻〉 and |ψ⁺〉. Compared to previous implementations for time-bin qubits, this yields an increase in the efficiency of Bell state analysis by a factor of thirty.

Real-world two-photon interference and proof-of-principle quantum key distribution immune to detector attacks.

Several vulnerabilities of single-photon detectors have recently been exploited to compromise the security of quantum-key-distribution (QKD) systems. In this Letter, we report the first proof-of-principle implementation of a new quantum-key-distribution protocol that is immune to any such attack. More precisely, we demonstrated this new approach to QKD in the laboratory over more than 80 km of spooled fiber, as well as across different locations within the city of Calgary. The robustness of our fiber-based implementation, together with the enhanced level of security offered by the protocol, confirms QKD as a realistic technology for safeguarding secrets in transmission. Furthermore, our demonstration establishes the feasibility of controlled two-photon interference in a real-world environment and thereby removes a remaining obstacle to realizing future applications of quantum communication, such as quantum repeaters and, more generally, quantum networks.

E-Selectin Targeted Gold Nanoshells to Inhibit Breast Cancer Cell Binding to Lung Endothelial Cells.

Extravasation of circulating tumor cells (CTCs) from the vasculature is a key step in cancer metastasis. CTCs bind to cell adhesion molecules (CAMs) expressed by endothelial cells (ECs) for flow arrest prior to extravasation. While a number of EC-expressed CAMs have been implicated in facilitating CTC binding, this work investigated the efficacy of inhibiting cancer cell binding to human lung microvascular ECs via antibody blocking of E-selectin using antibody-functionalized gold nanoshells (NS). The antibody-functionalized gold NS were synthesized using both directional and non-directional antibody conjugation techniques with variations in synthesis parameters (linker length, amount of passivating agents, and ratio of antibodies to NS) to gain a better understanding of these properties on the resultant hydrodynamic diameter, zeta potential, and antibody loading density. We quantified the ability of E-selectin antibody-functionalized NS to bind human lung microvascular endothelial cells (HMVEC-Ls) under non-inflamed and inflamed (TNF-α) conditions to inhibit binding of triple-negative MDA-MB-231s. E-selectin-targeted NS prepared using non-directional conjugation had higher antibody loading than those prepared via directional conjugation, resulting in the conjugates having similar overall binding to HMVEC-Ls at a given antibody concentration. E-selectin-targeted NS reduced MDA-MB-231 binding to HMVEC-Ls by up to 41% as determined using an in vitro binding assay. These results provide useful insights into the characteristics of antibody-functionalized NS prepared under different conditions while also demonstrating proof of concept that these conjugates hold potential to inhibit CTC binding to ECs, a critical step in extravasation during metastasis.

Arthrocentesis versus non-surgical intervention as initial treatment for temporomandibular joint arthralgia: a randomized controlled trial with long-term follow-up.

Arthrocentesis for arthralgia of the temporomandibular joint (TMJ) is often only indicated when conservative, non-surgical interventions have failed. However, performing arthrocentesis as initial therapy may facilitate earlier and better recuperation of the joint. The aim of this study was to assess the efficacy of this therapy with a long-term follow-up. Eighty-four patients were randomly allocated to receive either arthrocentesis as initial treatment (n = 41) or non-surgical intervention (n = 43). Pain (100-mm visual analogue scale, VAS) and mandibular function impairment questionnaire scores (MFIQ, 0-100) were recorded at 3, 12, and 26 weeks, and ≥ 5 years (median 6.2, interquartile range 5.6-7.4 years). Univariable analyses were performed and linear mixed-effect models were constructed. Patients in the arthrocentesis group experienced significantly lower TMJ arthralgia compared to those treated non-surgically (pain during movement: -10.23 mm (95% confidence interval -17.86; -2.60); pain at rest: - 8.39 mm (95% confidence interval -13.70; -3.08)), while mandibular function remained similar in the two groups (MFIQ -2.41 (95% confidence interval -8.61; 3.78)). Of the final sample, 10 patients (10/39, 26%) in the non-surgical intervention group and two patients (2/34, 6%) in the arthrocentesis group received additional treatment during follow-up. Thus, initial treatment with arthrocentesis reduced TMJ arthralgia more efficaciously than non-surgical intervention in the long term, while maintaining similar mandibular function.

[Oral health care volunteering in developing countries 2. Providing care effectively]. / Mondzorgvrijwilligerswerk in ontwikkelingslanden 2. Effectief zorgverlenen.

Oral health care volunteering in developing countries based on the traditional Western model does not contribute to sustainable improvement and has, presumably, negative consequences for the local health care system. The oral health care can and should be delivered more efficacious. To achieve efficacious and sustainable results, the 'Basis package of oral care' of the World Health Organization offers a good manual. In addition, the Dutch branch of Dental Health International can support non-governmental organizations in establishing volunteering oral health care delivery programmes in order to improve the preventive care, the accessibility of care, the working conditions of the local oral health care providers, and the medical hygiene.

[Oral health care volunteering in developing countries 1. More than charity]. / Mondzorgvrijwilligerswerk in ontwikkelingslanden 1. Meer dan liefdadigheid.

Although limited in extent, oral health care volunteering in developing countries can contribute to sustainable improvement of oral health. However, it is questionable whether traditional care delivery based on the Western model, which many volunteers apply, has a sustainable effect and, presumably, it has negative consequences for the local health care system in many developing countries. Four i's should be involved when trying to make tactful policy: 1. 'ideas' evidence-based interventions, 2. 'institutions', current regulatory processes and approvals of governments and participating societies, 3. 'interests', incentives and motives of societies to collaborate, 4. 'incidents', unexpected economic alterations in the country or an inspiring successful public prevention programme.

Disseminated Candidiasis caused by Candida albicans with amino acid substitutions in Fks1 at position Ser645 cannot be successfully treated with micafungin.

The clinical utility of the echinocandins is potentially compromised by the emergence of drug resistance. We investigated whether Candida albicans with amino acid substitutions at position Ser645 in Fks1 can be treated with either a conventional or an elevated dosage of micafungin. We studied Candida albicans (wild-type SC5314; MIC, 0.06 mg/liter) and four fks1 mutants (one FKS1/fks1 heterozygote mutant [MIC, 0.5 mg/liter] and three fks1/fks1 homozygous mutants [MICs for all, 2 mg/liter]) with a variety of amino acid substitutions at Ser645. The pharmacokinetic and pharmacodynamic relationships were characterized in a persistently neutropenic murine model of disseminated candidiasis. A mathematical model was fitted to all pharmacokinetic and pharmacodynamic data. This mathematical model was then used to "humanize" the murine pharmacokinetics, and the predicted antifungal effect was determined. The estimated maximal rate of growth and ultimate fungal densities in the kidney for each of the strains were similar. The administration of micafungin at 1 mg/kg of body weight to the wild type resulted in moderate antifungal activity, whereas the administration of 5 and 20 mg/kg resulted in rapid fungicidal activity. In contrast, the FKS1/fks heterozygote was killed only with 20 mg/kg, and the homozygous fks1 mutants failed to respond to any dosage. The bridging study revealed that human dosages of 100 and 400 mg/day were active only against the wild type, with no activity against either the heterozygote or the homozygote mutants. Ser645 Fks1 Candida albicans mutants cannot be treated with either conventional or elevated dosages of micafungin and should be deemed resistant.

Eomesodermin, HAND1, and CSH1 proteins are induced by cellular stress in a stress-activated protein kinase-dependent manner.

Eomesodermin (Eomes) is a transcription factor essential for trophoblast development. Stress stimuli activate stress-activated protein kinase (MAPK8/9) and modulate transcription factors in trophoblast stem cells (TSC). In this study, we test the hypothesis that stress-induced Eomes upregulation and downstream trophoblast development are MAPK8/9-dependent. Immunocytochemical and immunoblot assays suggest that Eomes is induced by hyperosmolar stress in a dose- and time-dependent manner. Two MAPK8/9 inhibitors that work by different mechanisms, LJNKl1 and SP600125, block induction of Eomes protein by stress. During normal TSC differentiation, the transcription factor heart and neural crest derivatives expressed 1 (HAND1) is dependent on Eomes, and chorionic somatomammotropin hormone 1 (CSH1) expression is dependent on HAND1. Similar to Eomes, HAND1 and CSH1 induction by stress are MAPK8/9-dependent, and CSH1 is induced in nearly all stressed TSC. CSH1 induction normally requires downregulation of the transcription factor inhibitor of differentiation 2 (ID2) as well as HAND1 upregulation. It was shown previously that hyperosmolar stress induces AMP-activated protein kinase (PRKAA1/2)-dependent ID2 loss in a MAPK8/9-independent manner. Inhibition of PRKAA1/2 with compound C and LJNKl1, more than MAPK8/9 inhibitors alone, inhibits the induction of CSH1 by stress. Taken together these data suggest that stress-induced MAPK8/9 and PRKAA1/2 regulate transcription factors Eomes/HAND1 and ID2, respectively. Together this network mediates induction of CSH1 by stress. Therefore, stress triggers a proportional increase in a normal early TSC differentiation event that could be adaptive in inducing CSH1. But the flexibility of TSC to undergo stress-induced differentiation could lead to pathophysiological consequences if stress endured and TSC differentiation became unbalanced.