Determining primary stability for adhesively stabilized dental implants.

OBJECTIVES To examine factors influencing the primary stability of dental implants when stabilized in over-sized osteotomies using a calcium phosphate-based adhesive cement was the objective. METHODS Using implant removal torque measurements as a surrogate for primary stability, we examined the influence of implant design features (diameter, surface area, and thread design), along with cement gap size and curing time, on the resulting primary implant stability. RESULTS Removal torque values scaled with implant surface area and increasing implant diameters. Cement gap size did not alter the median removal torque values; however, larger gaps were associated with an increased spread of the measured values. Among the removal torque values measured, all were found to be above 32 Ncm which is an insertion torque threshold value commonly recommended for immediate loading protocols. CONCLUSION The adhesive cement show potential for offering primary implant stability for different dental implant designs. In this study, the primary parameters influencing the measured removal torque values were the implant surface area and diameter. As the liquid cement prevents the use of insertion torque, considering the relationship between insertion and removal torque, removal torque can be considered a reliable surrogate for primary implant stability for bench and pre-clinical settings. CLINICAL RELEVANCE At present, the primary stability of dental implants is linked to the quality of the host bone, the drill protocol, and the specific implant design. The adhesive cement might find applications in future clinical settings for enhancing primary stability of implants under circumstances where this cannot be achieved conventionally

Prediction of depression in European general practice attendees: the PREDICT study

Background Prevention of depression must address multiple risk factors. Estimating overall risk across a range of putative risk factors is fundamental to prevention of depression. However, we lack reliable and valid methods of risk estimation. This protocol paper introduces PREDICT, an international research study to address this risk estimation. Methods/design This is a prospective study in which consecutive general practice attendees in six European countries are recruited and followed up after six and 12 months. Prevalence of depression is assessed at baseline and each follow-up point. Consecutive attendees between April 2003 and September 2004 who were aged 18 to 75 were asked to take part. The possibility of a depressive episode was assessed using the Depression Section of the Composite International Diagnostic Interview. A selection of presumed risk factors was based on our previous work and a systematic review of the literature. It was necessary to evaluate the test-retest reliability of a number of risk factor questions that were developed specifically, or adapted, for the PREDICT study. In a separate reliability study conducted between January and November 2003, consecutive general practice attendees in the six participating European countries completed the risk factor items on two occasions, two weeks apart. The overall response rate at entry to the study was 69%. We exceeded our expected recruitment rate, achieving a total of 10,048 people in all. Reliability coefficients were generally good to excellent. Discussion Response rate to follow-up in all countries was uniformly high, which suggests that prediction will be based on almost a full cohort. The results of our reliability analysis are encouraging and suggest that data collected during the course of PREDICT will have a satisfactory level of stability. The development of a multi-factor risk score for depression will lay the foundation for future research on risk reduction in primary care. Our data will also provide the necessary evidence base on which to develop and evaluate interventions to reduce the prevalence of depression

High-resolution late Holocene sedimentary cores record the long history of the city of Cádiz (south-western Spain)

Today, coastal cities worldwide are facing major changes resulting from climate change and anthropogenic forcing, which requires adaptation and mitigation strategies to be established. In this context, sedimentological archives in many Mediterranean cities record a multi-millennial history of environmental dynamics and human adaptation, revealing a long-lasting resilience. Founded by the Phoenicians around 3000 years ago, Cadiz (south-western Spain) is a key example of a coastal resilient city. This urban centre is considered to be one of the first cities of western Europe and has experienced major natural hazards during its long history, such as coastal erosion, storms, and also tsunamis (like the one in 1755 CE following the destructive Lisbon earthquake). In the framework of an international, joint archaeological and geoarchaeological project, three cores have been drilled in a marine palaeochannel that ran through the ancient city of Cadiz. These cores reveal a >= 50m thick Holocene sedimentary sequence. Importantly, most of the deposits date from the 1st millennium BCE to the 1st millennium CE. This exceptional sedimentary archive will allow our scientific team to achieve its research goals, which are (1) to reconstruct the palaeogeographical evolution of this specific coastal area; (2) to trace the intensity of activities of the city of Cadiz based on archaeological data, as well as geochemical and palaeoecological indicators; and (3) to identify and date high-energy event deposits such as storms and tsunami

Histological evaluation of osseointegration between conventional and novel bone-level tapered implants in healed bone-A preclinical study.

AIMS To histologically compare osseointegration and crestal bone healing between newly introduced tapered, self-cutting bone-level test implants and tapered bone-level control implants in sites with fully healed sites. METHODS Sixty-six implants (33 test, 33 control) were placed 1 mm subcrestally in a minipig model and underwent qualitative histologic and quantitative histometric analyses after 3, 6 and 12 weeks of submerged healing. The primary and secondary outcomes were the bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC). Outcomes between the test and control implants were statistically compared. RESULTS The BIC values of the test implants were comparable and non-inferior over the time points studied, except for the 12 weeks time point which showed statistically significantly higher BIC values of the test (88.07 ± 5.35%) compared to the control implants (80.88 ± 7.51%) (p = .010). Similarly comparable and non-inferior were the fBIC values, except for the 6-week outcome, which showed statistically higher values for the test (-546.5 ± 450.80 μm) compared to the control implants (-75.7 ± 100.59 μm). fBIC results for the test implants were qualitatively more stable and consistent between test time points. CONCLUSION Novel self-cutting bone-level test implants demonstrated superior osseointegration and similar bone levels compared to conventional bone-level implants after a healing period of 12 weeks in healed ridges

Thermal exposure of implant osteotomies and its impact on osseointegration—A preclinical in vivo study

Objectives: Thermal and mechanical stresses during osteotomy preparation can impair implant osseointegration. This study investigated implant osseointegration following the measurement of temperature exposure during osteotomy drilling, varying drill design, sequence, and drill wear. Materials and methods: 36 tapered implants were placed in a mandibular minipig model after guided drilling of implant osteotomies using 4 different groups: (1) control drills with a conservative, sequential drilling sequence, (2) control drills using a shortened drill sequence (PF), (3) novel test drill displaying an optimized drill design and surface treatment, PF, and (4) aged test drill, PF. Intraosseous temperatures during drilling were measured using a temperature probe. BIC, fBIC, and tissue reactions were histomorphometrically derived after 2 and 8 weeks of healing. Results: Compared to control drills (1) or (2), test drills (3) resulted in significantly lower maximum temperatures ((35.4 (CI 30.2–40.5)°C vs. (46.5 (CI 41.0–52.0)°C, p =.0021)) and shorter drill times ((4.5 (CI 1.6–7.3)sec vs. 10.3 (7.3–13.4)sec). Lower osteotomy temperature values and shorter drill times corroborated with significantly higher BIC after 2 and 8 weeks healing for the test (3) compared to control groups (2) (2 weeks: (44.9 (CI 34.1–55. 7)% vs. (31.3 (CI 20.5–42.2)%, p = <.0001 and 8 weeks: (73.7 (CI 64.2–83.2)% vs. (66.2 (CI 57.0–75.4)%, p = <.0455). Conclusion: The improved osseointegration of implants placed after osteotomy preparation with novel test drills using a shortened drill sequence compared to standard drills and conventional drill protocols might be attributed to more favorable thermal profiles and less mechanical stress exerted on the bone surrounding the implant osteotomy

Thermal exposure of implant osteotomies and its impact on osseointegration—A preclinical in vivo study

Objectives: Thermal and mechanical stresses during osteotomy preparation can impair implant osseointegration. This study investigated implant osseointegration following the measurement of temperature exposure during osteotomy drilling, varying drill design, sequence, and drill wear. Materials and methods: 36 tapered implants were placed in a mandibular minipig model after guided drilling of implant osteotomies using 4 different groups: (1) control drills with a conservative, sequential drilling sequence, (2) control drills using a shortened drill sequence (PF), (3) novel test drill displaying an optimized drill design and surface treatment, PF, and (4) aged test drill, PF. Intraosseous temperatures during drilling were measured using a temperature probe. BIC, fBIC, and tissue reactions were histomorphometrically derived after 2 and 8 weeks of healing. Results: Compared to control drills (1) or (2), test drills (3) resulted in significantly lower maximum temperatures ((35.4 (CI 30.2–40.5)°C vs. (46.5 (CI 41.0–52.0)°C, p =.0021)) and shorter drill times ((4.5 (CI 1.6–7.3)sec vs. 10.3 (7.3–13.4)sec). Lower osteotomy temperature values and shorter drill times corroborated with significantly higher BIC after 2 and 8 weeks healing for the test (3) compared to control groups (2) (2 weeks: (44.9 (CI 34.1–55. 7)% vs. (31.3 (CI 20.5–42.2)%, p = <.0001 and 8 weeks: (73.7 (CI 64.2–83.2)% vs. (66.2 (CI 57.0–75.4)%, p = <.0455). Conclusion: The improved osseointegration of implants placed after osteotomy preparation with novel test drills using a shortened drill sequence compared to standard drills and conventional drill protocols might be attributed to more favorable thermal profiles and less mechanical stress exerted on the bone surrounding the implant osteotomy

Apoptosis-inducing anti-HER2 agents operate through oligomerization-induced receptor immobilization

Overexpression of the receptor tyrosine kinase HER2 plays a critical role in the development of various tumors. Biparatopic designed ankyrin repeat proteins (bipDARPins) potently induce apoptosis in HER2-addicted breast cancer cell lines. Here, we have investigated how the spatiotemporal receptor organization at the cell surface is modulated by these agents and is distinguished from other molecules, which do not elicit apoptosis. Binding of conventional antibodies is accompanied by moderate reduction of receptor mobility, in agreement with HER2 being dimerized by the bivalent IgG. In contrast, the most potent apoptosis-inducing bipDARPins lead to a dramatic arrest of HER2. Dual-color single-molecule tracking revealed that the HER2 "lockdown" by these bipDARPins is caused by the formation of HER2-DARPin oligomer chains, which are trapped in nanoscopic membrane domains. Our findings establish that efficient neutralization of receptor tyrosine kinase signaling can be achieved through intermolecular bipDARPin crosslinking alone, resulting in inactivated, locked-down bipDARPin-HER2 complexes

Osseointegration of a novel injection molded 2-piece ceramic dental implant : a study in minipigs

Objectives: This study compared the osseointegrative potential of a novel injection molded zirconia dental implant (Neodent Zi ceramic implant, test) and a commercially available titanium implant (Neodent Alvim implant, control) in terms of histomorphometrically derived bone-to-implant contact (BIC), first bone-to-implant contact (fBIC), and the ratio of bone area to total area (BATA) around the implant. Materials and methods: A total of 36 implants, 18 per individual test device, were implanted in a split-mouth arrangement in either side of the edentulous and fully healed mandible of 6 minipigs. Histomorphometric analysis of BIC, fBIC, and BATA were performed 8 weeks post implantation and subjected to statistical non-inferiority testing. Surface characteristics of both implant types were compared in terms of contact angle, surface topography, and elemental composition. Results: BIC, fBIC, and coronal BATA values of test and control implants were statistically comparable and non-inferior. BIC values of 77.8 ± 6.9% vs. 80.7 ± 6.9% (p = 0.095) were measured for the test and control groups. fBIC lingual values were − 238 ± 328 μm compared with − 414 ± 511 μm (p = 0.121) while buccal values were − 429 ± 648 μm and − 588 ± 550 μm (p = 0.230) for the test and control devices, respectively. BATA in the apical segment was significantly higher in the test group compared with the control group (67.2 ± 11.8% vs. 59.1 ± 11.4%) (p = 0.0103). Surface topographies of both implant types were comparable. Surface chemical analysis indicated the presence of carbonaceous adsorbates which correlated with a comparable and predominantly hydrophobic character of the implants. Conclusion: The results demonstrate that the investigated zirconia implants, when compared with a commercially available titanium implant, show equivalent and non-inferior bone integration, bone formation, and alveolar bone level maintenance. This qualifies the investigated zirconia implant as a potential candidate for clinical development. Clinical relevance: This study investigated the osseointegration of a novel zirconia 2-piece dental implant prototype intended for clinical development. With the aim of translating this prototype into clinical development preclinical models, procedures and materials within this study have been selected as close to clinical practice and human physiological conditions as possible

A novel fully tapered, self-cutting tissue-level implant: non-inferiority study in minipigs.

OBJECTIVES To assess the osseointegration and crestal bone level maintenance of a novel fully tapered self-cutting tissue-level implant for immediate placement (test) compared to a clinically established tissue-level implant (control) in moderate bone quality. MATERIALS AND METHODS Test and control implants were compared in 3 groups, i.e., small-, medium-, and large-diameter implants in an edentulous mandibular minipig model with moderate bone quality after 12 weeks of healing. Histometrically derived bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC) were subjected to statistical non-inferiority testing. Maximum insertion torque values in artificial bone were assessed for comparison. RESULTS BIC values for the tests and control implants for all 3 diameters were comparable and non-inferior: small diameter (61.30 ± 10.63% vs. 54.46 ± 18.31%) (p=0.99), medium diameter (60.91 ± 14.42 vs. 54.68 ± 9.16) (p=0.55), and large diameter (45.60 ± 14.67 vs. 52.52 ± 14.76) (p=0.31). fBIC values for test implants were higher and non-inferior compared to control implants in all three groups. Test implants further showed distinctly higher maximum insertion torque values compared to control implants. CONCLUSION The investigated novel tissue-level implant is able to achieve high levels of primary and secondary implant stability under simultaneous preservation of crestal bone levels. This qualifies the studied implant as an attractive candidate for immediate placement in bone of limited quality. CLINICAL RELEVANCE This pilot pre-clinical study investigated a novel tissue-level implant for immediate placement. With the aim of translating the studied prototype into clinical application pre-clinical models, procedures and controls have been chosen with the aim of reflecting its future clinical indication and use

Decomposition and dewetting of super-saturated Cu-15 at. % Co solid solution film

International audienceNano-structured copper thin films present numerous applications for miniaturization of electronic devices. Their long term stability is key for reliable functionality. This work explores the thermal stability and solid state dewetting of a Cu-Co solid solution thin film and compares it to pure Cu. As according to the phase diagram Co is practically immiscible in Cu at room temperature, a metastable solid solution of Cu-15 at. % Co was deposited as thin film on a sapphire wafer. The microstructural evolution of the Co super-saturated film at temperatures ranging from 673 to 1073 K was evaluated using X-ray diffraction and high resolution microscopy techniques such as scanning electron and transmission electron microscopy. Interestingly, there is a competition between grain growth and phase separation. Co precipitates at grain boundaries acting as pinning sites preventing rapid grain growth during heat treatment at intermediate annealing temperature. However, grain growth occurs very quickly at higher temperatures, once the elemental phases of Cu and Co are formed. The competition between grain growth and phase separation and their consequence for dewetting are discussed