Quality of orthodontic care-A multicenter cohort study in Germany : Part 1: Evaluation of effectiveness of orthodontic treatments and predictive factors.

AIMS: Orthodontic care and its effectiveness have increasingly become the focus of political and public attention in the recent past. Therefore, this multicenter cohort study aimed to report about the effectiveness of orthodontic treatments in Germany and to identify potential influencing factors. METHODS: A total of 586 patients from seven German study centers were screened for this cohort study, of which 361 patients were recruited at the end of their orthodontic treatment. Of these, 26 patients had missing study models and/or missing treatment information. Thus, 335 participants were included. The severity of malocclusion was rated using the Peer Assessment Rating (PAR) Index at baseline (T0) retrospectively and-prospectively-after the retention period (T1). Practitioner-, treatment- and patient-related information were analyzed in order to detect potential predictive factors for treatment effectiveness. RESULTS: Study participants (202 female and 133 male) were on average 14.8 (standard deviation [SD] ± 6.1) years old at start of active treatment. Average PAR score at T0 was 25.96 (SD ± 10.75) and mean posttreatment PAR score was 3.67 (SD ± 2.98) at T1. An average decrease of total PAR score by 22.30 points (SD ± 10.73) or 83.54% (SD ± 14.58; p < 0.001) was detected. Furthermore, 164 treatments (49.1%) were categorized as 'greatly improved' but only 3 treatments (0.9%) as 'worse or no different'; 81.5% of all cases finished with a high-quality treatment outcome (≤5 PAR points at T1). Logistic regression analyses detected staff experience as a significant predictive factor for high-quality results (odds ratio 1.27, p = 0.001, 95% confidence interval 1.11-1.46). CONCLUSION: The improvement rate among this selected German cohort indicated an overall very good standard of orthodontic treatment. Staff experience proved to be a predictive factor for high-quality results.

Candidate Genes for Nonsyndromic Cleft Palate Detected by Exome Sequencing.

Nonsyndromic cleft palate only (nsCPO) is a facial malformation that has a livebirth prevalence of 1 in 2,500. Research suggests that the etiology of nsCPO is multifactorial, with a clear genetic component. To date, genome-wide association studies have identified only 1 conclusive common variant for nsCPO, that is, a missense variant in the gene grainyhead-like-3 ( GRHL3). Thus, the underlying genetic causes of nsCPO remain largely unknown. The present study aimed at identifying rare variants that might contribute to nsCPO risk, via whole-exome sequencing (WES), in multiply affected Central European nsCPO pedigrees. WES was performed in 2 affected first-degree relatives from each family. Variants shared between both individuals were analyzed for their potential deleterious nature and a low frequency in the general population. Genes carrying promising variants were annotated for 1) reported associations with facial development, 2) multiple occurrence of variants, and 3) expression in mouse embryonic palatal shelves. This strategy resulted in the identification of a set of 26 candidate genes that were resequenced in 132 independent nsCPO cases and 623 independent controls of 2 different ethnicities, using molecular inversion probes. No rare loss-of-function mutation was identified in either WES or resequencing step. However, we identified 2 or more missense variants predicted to be deleterious in each of 3 genes ( ACACB, PTPRS, MIB1) in individuals from independent families. In addition, the analyses identified a novel variant in GRHL3 in 1 patient and a variant in CREBBP in 2 siblings. Both genes underlie different syndromic forms of CPO. A plausible hypothesis is that the apparently nonsyndromic clefts in these 3 patients might represent hypomorphic forms of the respective syndromes. In summary, the present study identified rare variants that might contribute to nsCPO risk and suggests candidate genes for further investigation.

Influence of electrophysiological heterogeneity on electrical stimulation in healthy and failing human hearts.

The application of strong electrical stimuli is a common method used for terminating irregular cardiac behaviour. The study presents the influence of electrophysiological heterogeneity on the response of human hearts to electrical stimulation. The human electrophysiology was simulated using the ten Tusscher-Noble-Noble-Panfilov cell model. The anisotropic propagation of depolarisation in three-dimensional virtual myocardial preparations was calculated using bidomain equations. The research was carried out on different types of virtual cardiac wedge. The selection of the modelling parameters emphasises the influence of cellular electrophysiology on the response of the human myocardium to electrical stimulation. The simulations were initially performed on a virtual cardiac control model characterised by electrophysiological homogeneity. The second preparation incorporated the transmural electrophysiological heterogeneity characteristic of the healthy human heart. In the third model type, the normal electrophysiological heterogeneity was modified by the conditions of heart failure. The main currents responsible for repolarisation (Ito, IKs and IKI) were reduced by 25%. Successively, [Na+]i was increased by the regulation of the Na+-Ca2+ exchange function, and fibrosis was represented by decreasing electrical conductivity. Various electrical stimulation configurations were used to investigate the differences in the responses of the three different models. Monophasic and biphasic electrical stimuli were applied through rectangular paddles and needle electrodes. A whole systolic period was simulated. The distribution of the transmembrane voltage indicated that the modification of electrophysiological heterogeneity induced drastic changes during the repolarisation phase. The results illustrated that each of the heart failure conditions amplifies the modification of the response of the myocardium to electrical stimulation. Therefore a theoretical model of the failing human heart must incorporate all the characteristic features.

Bond strength of various fluoride-releasing orthodontic bonding systems. Experimental study.

The aim of the study was to compare the shear bond strength of a fluoride-releasing composite resin adhesive (Light Bond, Reliance) and a light-cured resin-reinforced glass ionomer cement (Fuji Ortho LC, GC America) bonded to extracted teeth under different enamel surface conditions. Forty human premolars were divided at random into 4 groups of 10 specimens. Stainless steel brackets were attached to the enamel surface by 1 of the 4 protocols: 1. Fuji Ortho LC, moist non-etched enamel; 2. Fuji Ortho LC, moist etched (37% H3PO4); 3. Light Bond, dry etched (37% H3PO4); 4. Light Bond, dry etched (Etch & Prime 3.0, Degussa). The teeth were stored in deionized water at 37 degrees C for 48 hours. Shear bond strengths was determined at a crosshead speed of 1 mm/min. The residual adhesive on the enamel surface was evaluated with the modified Adhesive Remnant Index (ARI). Analysis of variance (ANOVA) and Duncan's test were used to compare the 4 groups. Significance was predetermined at p = 0.05. Significant inter-group differences were found (p < 0.0001). The mean SBS (and SD), in MPa were: Group 1: 15.9 (4.7); Group 2: 20.3 (2.5); Group 3: 16.7 (2.6); Group 4: 11.7 (2.5). Glass ionomer cement without etching and composite with Etch & Prime showed adhesive failures at the enamel and good enamel integrity after debonding. The other specimens showed mixed or adhesive fractures at the bracket failure sites. Glass ionomer used on wet tooth surfaces without etching shows a clinically acceptable bond strength with clean separation from the enamel after debonding.

Bond strength of a fluoride-releasing bracket adhesive. Experimental study.

The aim of the study was to examine a new fluoride-releasing light-cured filling composite for its bonding and debonding qualities when used as a bracket adhesive. The material investigated was a hybrid composite containing a chemically modified fluoride apatite, which is claimed to provide the enamel with phosphate, calcium, and fluoride ions in the presence of an acid pH, recharging its resources of these ions through fluoride-containing toothpastes used in daily oral hygiene. Concurrently suitability as an enamel conditioner was tested in a new self-etching primer, which does not require water rinsing but is gently air dried instead. For comparison a conventional light-cure single-component adhesive was used together with 37% orthophosphoric acid. After application of the respective conditioners, mesh-backed metal brackets were bonded to 20 human premolars in each of the 2 adhesive groups and subjected to a shear test. Bond failure location was evaluated using the Adhesive Remnant Index (ARI). Average bond strength of the experimental bracket adhesive and the conventional etchant was 8.96 MPa. Conditioning with the self-etching primer led to a decrease of mean shear bond strength values to 6.55 MPa. Highest bond strength was determined in the control group (12.19 MPa). The bond strength results obtained in the shear test recommend the new material as a bracket adhesive to be used with orthophosphoric acid for etching.

Ionic interactions in crystalline bovine pancreatic ribonuclease A.

Isomorphous crystals (space group P3(2)21) of bovine pancreatic ribonuclease A (RNase A) were prepared at a pH of 5.5 in a series of high salt conditions, where both the nature of the ions and the ionic strength varied: 80% ammonium sulfate (mu = 12.5); 8 M sodium formate (mu = 8.0); 3 M NaCl, 30% ammonium sulfate (mu = 7.0); 3 M CsCl, 30% ammonium sulfate (mu = 7.0); and 2.5 M NaCl, 3.3 M sodium formate (mu = 5.8). These structures were independently refined to a resolution of 2.0 A or better with R-factors that range from 16.1% to 17.5%. A comparison of these six structures and the monoclinic crystal form of RNase A grown from alcohol shows that changes in ionic strength do not alter the secondary or tertiary structure and that there are no significant changes in intramolecular salt bridges. These findings support the notion that structures determined from crystals grown in high salt are representative of the overall structural and electrostatic features present under physiological conditions. While little effect was observed on the main chain conformation, several residues adopted different side chain conformations and altered hydrogen-bonding patterns, either as result of direct anion binding or more subtle indirect effects. Changes in the ionic composition of the mother liquor allowed for the occupancy of the active site with different anions. The direct observation of active site-bound chloride and formate anions supports the proposal that these species act as true competitive inhibitors of RNase A and not through nonspecific electrostatic effects. The identification of bound formate anions allowed for an experimental validation of computational-based functional group mapping techniques and suggests a useful modification to these approaches. Electrostatic surface potential calculations identify a nearly continuous band of positive potential, consistent with an extended binding site for polynucleotide ligands and substrates. The majority of these residues are not involved in salt bridges, which may facilitate binding to extended polynucleotide substrates. Selection of the appropriate solvent conditions results in an unoccupied active site, which will allow this crystal form to be used for the crystallographic study of productive ligand-binding modes.

Serological diagnosis of HIV infection: incidence, outcome and significance of partial reactions found in western blot analysis.

Between May 1986 and April 1987 routine screening for anti-HIV antibody was performed by enzyme immunoassay (EIA) on 3344 serum samples. The 1160 samples found positive or borderline were further analysed in Western blot (Wb). We analysed the frequency of different patterns of 'intermediate' Wb reactions (1-3 'specific' bands) and tried to determine their significance by searching for possible modifications of the pattern of reaction a few months later. Of 1160 Wb, 461 were clearly positive, 489 negative and 210 'intermediate'. The latter consisted of: 92 sera with anti-p24 (associated or not), 23 with anti-gp 120 and 160, 16 with anti-p55, 12 with anti-p41, 10 with anti-p65, eight with anti-p17 and four with anti-p31. A non-specific pattern was observed in the remaining 45. Of these sera, 46% were obtained from high risk subjects, 38% from persons without risk and in 16% no reliable information was available. In 30 subjects (24 with p24 and 6 with p41), a second sample was obtained about three months later. The reaction persisted in nine, was replaced by another in five, and disappeared in 15. One subject with anti-p41 in the first sample became clearly positive. In one of the 15 samples with disappearance of the reaction, the antigen p24 was present as the only sign of HIV infection. Later samples of this subject showed clear seroconversion. In many subjects with and without risk of exposure to HIV, the Wb gives an intermediate pattern of reactions (1-3 specific bands), that does not permit definitive conclusion on one single sample. Later controls are therefore necessary. Most of these reactions do not correspond to HIV infection.

[Humoral autoimmune reactions directed against autoantigens of the H-2 histocompatibility system in mice with developing Rauscher leukemia]. / Gumoral'nye autoimmunnye reaktsii myshei s razvivaiushchimsia leikozom Raushera, napravlennye protiv sobstvennykh antigenov gistosovmestimosti sistemy H-2.

Antibodies exhibiting a selective anti-H-2 haplotype reaction with thymic and splenic lymphocytes of intact mice were found in the sera of mice of the strains BALB/c, C57Bl/6, AKR and BDF1 with the developing Rauscher leukemia by applying the membrane immunofluorescent and complement-dependent cytotoxicity techniques in vitro. Monoclonal antibodies against H-2 IAd and H-2 IAk and sorption tests using lymphocytes of the congenic-resistant strains as target cells were used to show that the aforementioned antibodies acted against autoantigens which are the products of the genes of the I-subregion of the H-2 histocompatibility complex.

[Changes in the force-pCa characteristics of the striated muscles of the skate after treatment with phalloidin]. / Izmenenie kharakteristiki sila-pCa poperechno-polosatykh myshts skata pod vliianiem falloidina.

The pCa/tension relationship of glycerinated skate thoracic fin muscle was found to fit well in the Hill equation. Phalloidin has been shown to decrease calcium sensitivity (shift of pK to the lower pCa by 0.27 +/- 0.08), tension at saturated pCa by 22 +/- 5%, and Hill coefficient by 0.37 +/- 0.21. As F-actin structural motility is restricted by phalloidin, these results are in agreement with the idea of participation of F-actin conformational changes in its switching by calcium ions and in ensuring cooperativity of this process.

[Antilymphocytic humoral autoimmune response of mice with developing Rauscher leukemia directed against group-specific retrovirus antigens]. / Antilimfotsitarnye gumoral'nye autoimmunnye reaktsii myshei s razvivaiushchimsia leikozom Raushera, napravlennye protiv gruppospetsificheskikh antigenov retrovirusov.

The methods of indirect membrane immunofluorescence, immunoenzyme analysis, complement-dependent cytotoxicity and sorption tests were used to demonstrate two types of humoral antilymphocytic autoimmune reactions at the early stage of the Rauscher leukemia in mice of BALB/c, BDF1 and C57B1/6 strains. The first one is directed against group-specific oncoviral antigens (p30, p15) expressed on the lymphocyte membrane of both intact mice and of those with leukemia, the second one is virus-independent and possesses strain specificity.

Detection of anti-HTLV-III/LAV antibody by enzyme-linked immunosorbent assay in high-risk individuals in Switzerland 1974-1985.

Anti-HTLV-III antibody was tested in frozen sera from high-risk individuals, collected between 1974 and 1985 in Switzerland. All but one of the 262 sera of a control group were negative. Among drug addicts, none of the 78 samples collected from 1974 to 1979 was positive. Antibody was first detected in 1980 and thereafter with progressively increasing frequency. Three of 63 samples from 24 dialyzed patients who had received multiple transfusions showed borderline positive values. None of the seropositive subjects has developed AIDS or AIDS-related complex.

[Antibodies against interspecies erythrokaryocyte antigen in patients with partial red cell aplasia of the bone marrow]. / Antitela protiv mezhvidovogo antigena éritrokariotsitov u bol'nykh partsial'noi krasnokletochnoi aplaziei kostnogo mozga.

Immunofluorescense and cytotoxicity test in vitro were used to demonstrate specific antibodies in sera of 11 out of 19 patients with partial red cell aplasia (PRCA). The antibodies reacted with erythroblast cells from embryos and adult men, with bone marrow cells from a female patient suffering from acute erythroleukemia, with erythrokaryocytes of mouse embryos and cells of Rauscher's viral erythroleukemia. The results of cross adsorption and blockade of the immunofluorescent reaction of the sera of PRCA patients with antibodies against mouse erythroblast antigen bearing an interspecies determinant suggest that in the pathogenesis of PRCA there takes part an autoimmune reaction against specific interspecies antigen to erythrokaryocytes. This antigen is apparently similar to antigen against mouse erythroblast cells.

[Antigenic marker of human erythrokaryocytes similar to mouse erythroblastosis antigen]. / Antigennyi marker eritrokariotsitov cheloveka, skhodnyi s antigenom éritroblastov myshei.

Identical antigenic determinants are discovered on the surface of human erythrokaryocytes with antibodies against specific antigen of murine erythroblasts (Ag-Ed), previously revealed in study of Rauscher leukemia, in the immunofluorescent and cytotoxic tests. The antigen is present on the membranes of the majority of human embryonic liver and adult bone marrow nuclear erythroid cells, but is not found in fetal thymocytes, newborn kidney cells, adult human hepatic cells and in peripheral blood erythrocytes. Ag-Eb appears to possess an inter-species determinant, shared by mammalian nuclear erythroid cells, and may be used as their specific marker.