Early implant placement with simultaneous guided bone regeneration following single-tooth extraction in the esthetic zone: 12-month results of a prospective study with 20 consecutive patients

BACKGROUND: Early implant placement is one of the treatment options in postextraction sites in the anterior maxilla. Implant placement is performed after a soft tissue healing period of 4 to 8 weeks. Implant placement is combined with a simultaneous guided bone regeneration (GBR) procedure to rebuild esthetic facial hard and soft tissue contours. METHODS: In this prospective case-series study, 20 consecutive patients treated with an implant-borne single crown were prospectively followed for 12 months. Clinical, radiologic, and esthetic parameters were recorded to assess treatment outcomes. RESULTS: At the 12-month examination, all 20 implants were successfully integrated, demonstrating ankylotic stability and healthy peri-implant soft tissues as documented by standard parameters. The esthetic outcomes assessed by a pink esthetic score (PES) and a white esthetic score (WES) demonstrated pleasing results overall. The WES values were slightly superior to the PES values. The periapical radiographs showed minimal crestal bone loss around the used bone level implants, with mean bone loss of 0.18 mm at 12 months. Only one implant showed >0.5 mm bone loss, combined with minor mucosal recession of 0.5 to 1.0 mm. CONCLUSIONS: This prospective case series study evaluating the concept of early implant placement demonstrated successful tissue integration for all 20 implants. The short-term follow-up of 12 months revealed pleasing esthetic outcomes overall, as assessed by objective parameters. The risk for mucosal recession was low; only one patient showed minor recession of the facial mucosa. These encouraging results need to be confirmed with 3- and 5-year follow-up examinations.

Stability after bilateral sagittal split osteotomy advancement surgery with rigid internal fixation: a systematic review

PURPOSE: The purpose of this systematic review was to evaluate horizontal relapse and its causes in bilateral sagittal split advancement osteotomy (BSSO) with rigid internal fixation of different types. MATERIALS AND METHODS: A search of the literature was performed in the databases PubMed, Ovid, Cochrane Library, and Google Scholar Beta. From 488 articles identified, 24 articles were finally included. Six studies were prospective, and 18 were retrospective. The range of postoperative study records was 6 months to 12.7 years. RESULTS: The short-term relapse for bicortical screws was between 1.5% and 32.7%, for miniplates between 1.5% and 18.0%, and for bioresorbable bicortical screws between 10.4% and 17.4%, at point B. The long-term relapse for bicortical screws was between 2.0% and 50.3%, and for miniplates between 1.5% and 8.9%, at point B. CONCLUSIONS: BSSO for mandibular advancement is a good treatment option for skeletal Class II, but seems less stable than BSSO setback in the short and long terms. Bicortical screws of titanium, stainless steel, or bioresorbable material show little difference regarding skeletal stability compared with miniplates in the short term. A greater number of studies with larger skeletal long-term relapse rates were evident in patients treated with bicortical screws instead of miniplates. The etiology of relapse is multifactorial, involving the proper seating of the condyles, the amount of advancement, the soft tissue and muscles, the mandibular plane angle, the remaining growth and remodeling, the skill of the surgeon, and preoperative age. Patients with a low mandibular plane angle have increased vertical relapse, whereas patients with a high mandibular plane angle have more horizontal relapse. Advancements in the range of 6 to 7 mm or more predispose to horizontal relapse. To obtain reliable scientific evidence, further short-term and long-term research into BSSO advancement with rigid internal fixation should exclude additional surgery, ie, genioplasty or maxillary surgery, and include a prospective study or randomized clinical trial design with correlation statistics.

Hsp90 transcriptionally and post-translationally regulates the expression of NDRG1 and maintains the stability of its modifying kinase GSK3beta

N-myc downstream-regulated gene 1 (NRDG1) is a stress-induced protein whose putative function is suppression of tumor metastasis. A recent proteonomic study showed NDRG1 interacts with the molecular chaperone heat shock protein 90 (Hsp90). From their reported association, we investigated if NDRG1 is dependent on Hsp90 for its stability and is therefore a yet unidentified Hsp90 client protein. Here, we demonstrate that endogenous NDRG1 and Hsp90 physically associate in hepatocellular cancer cell lines. However, geldanamycin (GA)-mediated inhibition of Hsp90 did not disrupt their interaction or result in NDRG1 protein destabilization. On the contrary, inhibition of Hsp90 led to a transcriptional increase of NDRG1 protein which was associated with cell growth arrest. We also observed that GA inhibited the phosphorylation of NDRG1 by targeting its regulating kinases, serum- and glucocorticoid-induced kinase 1 (SGK1) and glycogen synthase kinase 3 beta (GSK3beta). We demonstrate that in the presence of GA, GSK3beta protein and activity were decreased thus indicating that Hsp90 is necessary for GSK3beta stability. Taken together, our data demonstrate that NDRG1 is not a classic client protein but interacts with Hsp90 and is still dually regulated by Hsp90 at a transcriptional and post-translational level. Finally, we suggest for the first time GSK3beta as a new client protein of Hsp90.

Quantifying the influence of bone density and thickness on resonance frequency analysis: an in vitro study of biomechanical test materials

PURPOSE: Resonance frequency analysis (RFA) offers the opportunity to monitor the osseointegration of an implant in a simple, noninvasive way. A better comprehension of the relationship between RFA and parameters related to bone quality would therefore help clinicians improve diagnoses. In this study, a bone analog made from polyurethane foam was used to isolate the influences of bone density and cortical thickness in RFA. MATERIALS AND METHODS: Straumann standard implants were inserted in polyurethane foam blocks, and primary implant stability was measured with RFA. The blocks were composed of two superimposed layers with different densities. The top layer was dense to mimic cortical bone, whereas the bottom layer had a lower density to represent trabecular bone. Different densities for both layers and different thicknesses for the simulated cortical layer were tested, resulting in eight different block combinations. RFA was compared with two other mechanical evaluations of primary stability: removal torque and axial loading response. RESULTS: The primary stability measured with RFA did not correlate with the two other methods, but there was a significant correlation between removal torque and the axial loading response (P < .005). Statistical analysis revealed that each method was sensitive to different aspects of bone quality. RFA was the only method able to detect changes in both bone density and cortical thickness. However, changes in trabecular bone density were easier to distinguish with removal torque and axial loading than with RFA. CONCLUSIONS: This study shows that RFA, removal torque, and axial loading are sensitive to different aspects of the bone-implant interface. This explains the absence of correlation among the methods and proves that no standard procedure exists for the evaluation of primary stability.

Quality controls for two heel bone ultrasounds used in the Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk Study

Because of the important morbidity and mortality associated with osteoporosis, it is essential to detect subjects at risk by screening methods, such as bone quantitative ultrasounds (QUSs). Several studies showed that QUS could predict fractures. None, however, compared prospectively different QUS devices, and few data of quality controls (QCs) have been published. The Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture Risk is a prospective multicenter study that compared three QUSs for the assessment of hip fracture risk in a population of 7609 women age >/=70 yr. Because the inclusion phase lasted 20 mo, and because 10 centers participated in this study, QC became a major issue. We therefore developed a QC procedure to assess the stability and precision of the devices, and for their cross-calibration. Our study focuses on the two heel QUSs. The water bath system (Achilles+) had a higher precision than the dry system (Sahara). The QC results were highly dependent on temperature. QUS stability was acceptable, but Sahara must be calibrated regularly. A sufficient homogeneity among all the Sahara devices could be demonstrated, whereas significant differences were found among the Achilles+ devices. For speed of sound, 52% of the differences among the Achilles+ was explained by the water s temperature. However, for broadband ultrasound attenuation, a maximal difference of 23% persisted after adjustment for temperature. Because such differences could influence measurements in vivo, it is crucial to develop standardized phantoms to be used in prospective multicenter studies.

Three-dimensional primary stability of cementless femoral stems

OBJECTIVE: This study investigates by means of a new bone-prosthesis interface motion detector whether conceptual design differences of femoral stems are reflected in their primary stability pattern. DESIGN: An in vitro experiment using a biaxial materials testing machine in combination with three-dimensional motion measurement devices was performed. BACKGROUND: Primary stability of uncemented total hip replacements is considered to be a prerequisite for the quality of bony ongrowth to the femoral stem. Dynamic motion as a response to loading as well as total motion of the prosthesis have to be considered under quasi-physiological cyclic loading conditions. METHODS: Seven paired fresh cadaveric femora were used for the testing of two types of uncemented femoral stems with different anchoring concepts: CLS stem (Spotorno) and Cone Prosthesis (Wagner). Under sinusoidal cyclic loading mimicking in vivo hip joint forces a new measurement technique was applied allowing for the analysis of the three-dimensional interface motion. RESULTS: Considerable differences between the two prostheses could be detected both in their dynamic motion and total motion behaviour. Whereas the CLS stem, due to the wedge-shaped concept, provides smaller total motions, the longitudinal ribs of the Cone prostheses result in a substantially smaller dynamic motion. CONCLUSIONS: The measuring technique provided reliable and accurate data illustrating the three-dimensional interface motion of uncemented femoral stems.

Single Molecular Conductance of Tolanes: Experimental and Theoretical Study on the Junction Evolution Dependent on the Anchoring Group

Employing a scanning tunneling microscopy based beak junction technique and mechanically controlled break junction experiments, we investigated tolane (diphenylacetylene)-type single molecular junctions having four different anchoring groups (SH, pyridyl (PY), NH2, and CN) at a solid/liquid interface. The combination of current–distance and current–voltage measurements and their quantitative statistical analysis revealed the following sequence for junction formation probability and stability: PY > SH > NH2 > CN. For all single molecular junctions investigated, we observed the evolution through multiple junction configurations, with a particularly well-defined binding geometry for PY. The comparison of density functional theory type model calculations and molecular dynamics simulations with the experimental results revealed structure and mechanistic details of the evolution of the different types of (single) molecular junctions upon stretching quantitatively.

Long-term stability of early implant placement with contour augmentation

In this prospective case series study, 20 patients with an implant-borne single crown following early implant placement with simultaneous contour augmentation were followed for 6 years. Clinical, radiologic, and esthetic parameters were assessed. In addition, cone beam computed tomography (CBCT) was used at 6 years to examine the facial bone wall. During the study period, all 20 implants were successfully integrated, and the clinical parameters remained stable over time. Pleasing esthetic outcomes were noted, as assessed by the pink esthetic scores. None of the implants developed mucosal recession of 1 mm or more. The periapical radiographs yielded stable peri-implant bone levels, with a mean DIB of 0.44 mm at 6 years. The CBCT scans showed that all 20 implants had a detectable facial bone wall at 6 years, with a mean thickness of around 1.9 mm. In summary, this prospective case series study demonstrated stable peri-implant hard and soft tissues for all 20 implants, and pleasing esthetic outcomes overall. The follow-up of 6 years confirmed that the risk for mucosal recession is low with early implant placement. In addition, contour augmentation with guided bone regeneration (GBR) was able to establish and maintain a facial bone wall in all 20 patients.

Reliability and stability of lucid dream and nightmare frequency scales

Lucid dream and nightmare frequencies vary greatly between individuals and to assess these differences reliable instruments are needed. The present study aimed to examine the reliability of eight-point scales for measuring lucid dream and nightmare frequencies. The scales were administered twice (with a four-week interval) to 93 sport students. A re-test reliability for the lucid dream frequency was found r=.89 (p<.001) and for the nightmare frequency r=.75 (p<.001). Both eight-point scales appear to be reliable measures for assessing individual differences in lucid dream and nightmare frequencies.

Epigenetic diversity increases the productivity and stability of plant populations

Biological diversity within species can be an important driver of population and ecosystem functioning. Until now, such within-species diversity effects have been attributed to underlying variation in DNA sequence. However, within-species differences, and thus potentially functional biodiversity, can also be created by epigenetic variation. Here, we show that epigenetic diversity increases the productivity and stability of plant populations. Epigenetically diverse populations of Arabidopsis thaliana produce up to 40% more biomass than epigenetically uniform populations. The positive epigenetic diversity effects are strongest when populations are grown together with competitors and infected with pathogens, and they seem to be partly driven by complementarity among epigenotypes. Our study has two implications: first, we may need to re-evaluate previous within-species diversity studies where some effects could reflect epigenetic diversity; second, we need to incorporate epigenetics into basic ecological research, by quantifying natural epigenetic diversity and testing for its ecological consequences across many different species.

A novel technique, dynamic intraligamentary stabilization creates optimal conditions for primary ACL healing: A preliminary biomechanical study

BACKGROUND Anterior cruciate ligament (ACL) rupture is a common lesion. Current treatment emphasizes arthroscopic ACL reconstruction via a graft, although this approach is associated with potential drawbacks. A new method of dynamic intraligamentary stabilization (DIS) was subjected to biomechanical analysis to determine whether it provides the necessary knee stability for optimal ACL healing. METHODS Six human knees from cadavers were harvested. The patellar tendon, joint capsule and all muscular attachments to the tibia and femur were removed, leaving the collateral and the cruciate ligaments intact. The knees were stabilized and the ACL kinematics analyzed. Anterior-posterior (AP) stability measurements evaluated the knees in the following conditions: (i) intact ACL, (ii) ACL rupture, (iii) ACL rupture with primary stabilization, (iv) primary stabilization after 50 motion cycles, (v) ACL rupture with DIS, and (vi) DIS after 50 motion cycles. RESULTS After primary suture stabilization, average AP laxity was 3.2mm, which increased to an average of 11.26mm after 50 movement cycles. With primary ACL stabilization using DIS, however, average laxity values were consistently lower than those of the intact ligament, increasing from an initial AP laxity of 3.00mm to just 3.2mm after 50 movement cycles. CONCLUSIONS Dynamic intraligamentary stabilization established and maintained close contact between the two ends of the ruptured ACL, thus ensuring optimal conditions for potential healing after primary reconstruction. The present ex vivo findings show that the DIS technique is able to restore AP stability of the knee.

In situ dehydration behavior of veszelyite (Cu,Zn)2Zn(PO4)(OH)3·2H2O: A single-crystal X-ray study

The rare mixed copper-zinc phosphate mineral veszelyite (Cu,Zn)2Zn(PO4)(OH)3·2H2O space group P21/c, a = 7.5096(2), b = 10.2281(2), c = 9.8258(2) Å, β = 103.3040(10)°, V = 734.45(3) Å3 was investigated by in situ temperature-dependent single-crystal X-ray structure refinements. The atomic arrangement of veszelyite consists of an alternation of octahedral and tetrahedral sheets. The Jahn-Teller distorted CuO6 octahedra form sheets with eight-membered rings. The tetrahedral sheet composed of PO4 and ZnO3(OH) tetrahedra shows strong topological similarities to that of cavansite, gismondine, and kipushite.Diffraction data of a sample from Zdravo Vrelo, near Kreševo (Bosnia and Herzegovina) have been measured in steps of 25 up to 225 °C. Hydrogen positions and the hydrogen-bond system were determined experimentally from the structure refinements of data collected up to 125 °C. At 200 °C, the hydrogen-bonding scheme was inferred from bond-valence calculations and donor-acceptor distances. The hydrogen-bond system connects the tetrahedral sheet to the octahedral sheet and also braces the Cu sheet.At 150 °C, the H2O molecule at H2O2 was released and the Cu coordination (Cu1 and Cu2) decreased from originally six- to fivefold. Cu1 has a square planar coordination by four OH groups and an elongate distance to O3, whereas Cu2 has the Jahn-Teller characteristic elongate bond to H2O1. The unit-cell volume decreased 7% from originally 734.45(3) to 686.4(4) Å3 leading to a formula with 1 H2O pfu. The new phase observed above 150 °C is characterized by an increase of the c axis and a shortening of the b axis. The bending of T-O-T angles causes an increasing elliptical shape of the eight-membered rings in the tetrahedral and octahedral sheets. Moreover a rearrangement of the hydrogen-bond system was observed.At 225 °C, the structure degrades to an X-ray amorphous residual due to release of the last H2O molecule at H2O1. The stronger Jahn-Teller distortion of Cu1 relative to Cu2 suggests that Cu1 is fully occupied by Cu, whereas Cu2 bears significant Zn. H2O1 is the fifth ligand of Cu2. Zn at Cu2 is not favorable to adopt planar fourfold coordination. Thus, if the last water molecule is expelled the structure is destabilized.This study contributes to understanding the dehydration mechanism and thermal stability of supergene minerals characterized by Jahn-Teller distorted octahedra with mixed Cu, Zn occupancy.

Promises of cyclotron-produced 44Sc as a diagnostic match for trivalent β--emitters: in vitro and in vivo study of a 44Sc-DOTA-folate conjugate

In recent years, implementation of 68Ga-radiometalated peptides for PET imaging of cancer has attracted the attention of clinicians. Herein, we propose the use of 44Sc (half-life = 3.97 h, average β+ energy [Eβ+av] = 632 keV) as a valuable alternative to 68Ga (half-life = 68 min, Eβ+av = 830 keV) for imaging and dosimetry before 177Lu-based radionuclide therapy. The aim of the study was the preclinical evaluation of a folate conjugate labeled with cyclotron-produced 44Sc and its in vitro and in vivo comparison with the 177Lu-labeled pendant. Methods: 44Sc was produced via the 44Ca(p,n)44Sc nuclear reaction at a cyclotron (17.6 ± 1.8 MeV, 50 μA, 30 min) using an enriched 44Ca target (10 mg 44CaCO3, 97.00%). Separation from the target material was performed by a semiautomated process using extraction chromatography and cation exchange chromatography. Radiolabeling of a DOTA-folate conjugate (cm09) was performed at 95°C within 10 min. The stability of 44Sc-cm09 was tested in human plasma. 44Sc-cm09 was investigated in vitro using folate receptor–positive KB tumor cells and in vivo by PET/CT imaging of tumor-bearing mice Results: Under the given irradiation conditions, 44Sc was obtained in a maximum yield of 350 MBq at high radionuclide purity (>99%). Semiautomated isolation of 44Sc from 44Ca targets allowed formulation of up to 300 MBq of 44Sc in a volume of 200–400 μL of ammonium acetate/HCl solution (1 M, pH 3.5–4.0) within 10 min. Radiolabeling of cm09 was achieved with a radiochemical yield of greater than 96% at a specific activity of 5.2 MBq/nmol. In vitro, 44Sc-cm09 was stable in human plasma over the whole time of investigation and showed folate receptor–specific binding to KB tumor cells. PET/CT images of mice injected with 44Sc-cm09 allowed excellent visualization of tumor xenografts. Comparison of cm09 labeled with 44Sc and 177Lu revealed almost identical pharmacokinetics. Conclusion: This study presents a high-yield production and efficient separation method of 44Sc at a quality suitable for radiolabeling of DOTA-functionalized biomolecules. An in vivo proof-of-concept study using a DOTA-folate conjugate demonstrated the excellent features of 44Sc for PET imaging. Thus, 44Sc is a valid alternative to 68Ga for imaging and dosimetry before 177Lu-radionuclide tumor therapy.

Surface charge of polymer coated SPIONs influences the serum protein adsorption, colloidal stability and subsequent cell interaction in vitro

It is known that the nanoparticle-cell interaction strongly depends on the physicochemical properties of the investigated particles. In addition, medium density and viscosity influence the colloidal behaviour of nanoparticles. Here, we show how nanoparticle-protein interactions are related to the particular physicochemical characteristics of the particles, such as their colloidal stability, and how this significantly influences the subsequent nanoparticle-cell interaction in vitro. Therefore, different surface charged superparamagnetic iron oxide nanoparticles were synthesized and characterized. Similar adsorbed protein profiles were identified following incubation in supplemented cell culture media, although cellular uptake varied significantly between the different particles. However, positively charged nanoparticles displayed a significantly lower colloidal stability than neutral and negatively charged particles while showing higher non-sedimentation driven cell-internalization in vitro without any significant cytotoxic effects. The results of this study strongly indicate therefore that an understanding of the aggregation state of NPs in biological fluids is crucial in regards to their biological interaction(s).

Denaturation and unfolding of human anaphylatoxin C3a: an unusually low covalent stability of its native disulfide bonds.

The complement C3a anaphylatoxin is a major molecular mediator of innate immunity. It is a potent activator of mast cells, basophils and eosinophils and causes smooth muscle contraction. Structurally, C3a is a relatively small protein (77 amino acids) comprising a N-terminal domain connected by 3 native disulfide bonds and a helical C-terminal segment. The structural stability of C3a has been investigated here using three different methods: Disulfide scrambling; Differential CD spectroscopy; and Reductive unfolding. Two uncommon features regarding the stability of C3a and the structure of denatured C3a have been observed in this study. (a) There is an unusual disconnection between the conformational stability of C3a and the covalent stability of its three native disulfide bonds that is not seen with other disulfide proteins. As measured by both methods of disulfide scrambling and differential CD spectroscopy, the native C3a exhibits a global conformational stability that is comparable to numerous proteins with similar size and disulfide content, all with mid-point denaturation of [GdmCl](1/2) at 3.4-5M. These proteins include hirudin, tick anticoagulant protein and leech carboxypeptidase inhibitor. However, the native disulfide bonds of C3a is 150-1000 fold less stable than those proteins as evaluated by the method of reductive unfolding. The 3 native disulfide bonds of C3a can be collectively and quantitatively reduced with as low as 1mM of dithiothreitol within 5 min. The fragility of the native disulfide bonds of C3a has not yet been observed with other native disulfide proteins. (b) Using the method of disulfide scrambling, denatured C3a was shown to consist of diverse isomers adopting varied extent of unfolding. Among them, the most extensively unfolded isomer of denatured C3a is found to assume beads-form disulfide pattern, comprising Cys(36)-Cys(49) and two disulfide bonds formed by two pair of consecutive cysteines, Cys(22)-Cys(23) and Cys(56)-Cys(57), a unique disulfide structure of polypeptide that has not been documented previously.