Capacity of coronal dentin to increase fiberglass post retention: a pull-out test

PURPOSE: To evaluate the capacity of residual dentin in the coronal part of the root canal to increase the retention of serrated fiberglass posts (Extra-glass P-6%). METHODS: 40 freshly-extracted maxillary central incisors were randomly and evenly divided into four test groups (TGs) with no (TG0), one (TG1), two (TG2) and three (TG3) coronal walls, respectively. After shaping, the canals were filled with gutta-percha and prepared to receive fiberglass posts. Coronal wall dentin was etched with 38% phosphoric acid for 60 seconds, rinsed, and dried. Dentin bonding agent (Prime & Bond NT) was applied, and fiberglass posts were luted for 8 mm into the post space using a self-cure composite (ResiLute). All samples were then subjected to tensile forces in a universal testing machine. Data were analyzed with ANOVA and Student t-tests (P< 0.01). RESULTS: The samples with residual coronal dentin showed higher bond strength than the samples without residual crown walls (TG0=100.30N; TG1=201.83N; TG2=263.54N; TG3=278.86N). The differences between the groups were all statistically significant at P< 0.01, except for the difference in tensile strength between TG2 and TG3, which was not statistically significant. Residual crown walls significantly increased the tensile load required to displace the posts.     

Terthiophene-promoted electropolymerization of 3-methylthiophene is heterogeneous electrocatalysis of polyterthiophene. A general electrocatalytic mechanism

The electrochemical oxidative polymerization of 3-methylthiophene (3MT) on platinum electrodes is favoured by the presence of previously deposited polyterthiophene (PTT) films. Cyclic voltammetry CV and single sweep voltammetry SSV were used to investigate the electrocatalytic process. The CV rate of polymer growth and the SSV electrocatalytic current increase linearly with the amount of predeposited PTT. The results rule out the previously invoked electrocatalytic promotion of 3MT polymerization by terthiophene radical cations in solution. SSV analysis with other thiophene-based polymer films (e.g. 3- and 3,4-alkylsubstituted polythiophenes) and with other thiophene-based monomers (e.g. 3,4-ethylenedioxythiophene) has shown that the electrocatalytic effect is of a general nature. The formation of a charge transfer complex between the thiophene-based monomer and the oxidized thiophene-based polymer is invoked to account for the catalytic action. The results account for the previous large and unexplained body of experimental evidence of electrocatalytic effects in the electro oxidative synthesis of conducting polymers.     

Surgical approaches to cavernous haemangiomas of the orbit

Cavernous haemangiomas are the most common orbital masses and the second most common cause of unilateral proptosis after thyroid ophthalmopathy. We retrospectively analysed 19 patients with retrobulbar cavernous haemangiomas, 9 of whom had lateral orbitotomy to remove retrobulbar cavernous haemangiomas located superior (n=4), inferior (n=2) or lateral (n=3) to the optic nerve. Seven patients had lateral orbitotomy together with an anterior medial approach to gain access to retrobulbar cavernous haemangiomas located medially to the optic nerve in the posterior half of the orbit. An anterior approach was used in 3 patient with an anteriorly located cavernous haemangioma. We describe here the planning of surgical treatment based on the site of the lesion.     

Le alterazioni tissutali dell'Articolazione Temporomandibolare a seguito della variazione della dimensione verticale nell'esperimento animale

Zusammenfassung Die Verfasser haben im Tierexperiment die nach Änderung der vertikalen Dimension eingetretenen Gewebsveränderungen am Kiefergelenk untersucht. Bei zwei Macacus-nemestrinus-Affen ist das okklusale Verhältnis in der vertikalen Richtung durch Extraktion der Zähne einer Kieferhälfte bzw. durch Einsetzen einer festsitzenden Prothese mit erhöhtem Okklusalrelief verändert worden. Durch die abgeänderte Kondylendynamik sind im Rahmen des Kiefergelenks Veränderungen hervorgerufen worden, welche an Hand von Schichtaufnahmen sowie makroskopisch und histologisch erörtert wurden.Es zeigt sich im Bereich des Kiefergelenkes des ersten Versuchstieres links und rechts das Bild einer Osteomalazie mit Verdünnung der Knochenbalken und Blutfülle in den Markräumen, eine asbestartige Metamorphose, ein Übergangsgewebe gleich dem Knochen- und Knorpelgewebe und eine Verdickung des Meniskus.Das sogenannte Übergangsgewebe im Kondylus spricht wahrscheinlich für eine Wucherung des skelettbildenden Gewebes als metaplastischen Verknöcherungsvorgang.Im zweiten Versuchstier äußert sich das Bild einer Osteosklerose, die hauptsächlich am rechten Kiefergelenk wahrscheinlich mit dem erhöhten vertikalen Dimensionsverhältnis in Beziehung steht, wobei jedoch die Wichtigkeit des metabolischen Stoffwechsels angesichts des höheren Alters des zweiten Versuchstieres im Vergleich zum ersten jüngeren nicht unterschätzt werden soll.Obwohl diese Schäden das pathogenetische Moment nicht erklären, sind Verfasser der Meinung, daß sie der veränderten Kondylendynamik zuzuschreiben sind als Folge der durch den Verlust der hinteren okklusalen Stütze herabgesetzten vertikalen Dimension.

---

---

Herrn Prof. Dr. Dr. G. Korkhaus zum 70. Geburtstag gewidmet

---

Con 23 Figure

---

Vortrag gehalten zum VII. Nationalkongreß der S.I.O.C.M.F. in Padua vom 28. bis 30. Mai 1964.     

Understanding the frustration arising from the competition between function,misfolding, and aggregation in a globular protein

Folding and function may impose different requirements on the amino acid sequences of proteins, thus potentially giving rise to conflict. Such a conflict, or frustration, can result in the formation of partially misfolded intermediates that can compromise folding and promote aggregation. We investigate this phenomenon by studying frataxin, a protein whose normal function is to facilitate the formation of iron–sulfur clusters but whose mutations are associated with Friedreich’s ataxia. To characterize the folding pathway of this protein we carry out a Φ-value analysis and use the resulting structural information to determine the structure of the folding transition state, which we then validate by a second round of rationally designed mutagenesis. The analysis of the transition-state structure reveals that the regions involved in the folding process are highly aggregation-prone. By contrast, the regions that are functionally important are partially misfolded in the transition state but highly resistant to aggregation. Taken together, these results indicate that in frataxin the competition between folding and function creates the possibility of misfolding, and that to prevent aggregation the amino acid sequence of this protein is optimized to be highly resistant to aggregation in the regions involved in misfolding.Frustration is a general condition that arises in the presence of conflicting requirements. A system is frustrated when it is impossible to fully minimize its energy by optimizing simultaneously all of the possible interactions among its components (1). Although complex systems tend in general to exhibit frustration because of the large number and heterogeneity of their components, protein molecules are remarkable in that their folding process involves interactions that express a minimal level of frustration. According to the so-called principle of minimal frustration, the energy of proteins decreases as they explore conformations increasingly similar in structure to the native state (2). Consequently, the free energy landscape of proteins is characterized by the presence of a well-defined global minimum and very few other local minima, which are typically intermediate states along the folding pathway. This organization of conformational space normally ensures rapid and reliable folding (2–6).Proteins, however, have evolved not only to fold, but also to function. Because the evolutionary constraints that select for a given function may be in conflict with the folding process, it is possible that local frustration patterns may localize in specific regions of proteins, in particular in their active sites. Indeed, a statistical survey of different proteins has shown that frustrated interactions tend to cluster at binding sites and that such frustration decreases upon complex formation (7). Because frustration is associated with the presence of local minima in the free energy landscape, it is important to understand how proteins have evolved to minimize the possible effects associated with these local minima, which are likely to contain misfolded elements and thus to potentially give rise to aggregation.To address this question we studied frataxin, a mitochondrial protein that binds both Fe²⁺ and Fe³⁺ ions and forms a ternary complex with the two main components of the iron–sulfur cluster biogenesis machinery (8–11). This protein offers good opportunities for investigating the relationships between folding, misfolding, and disease. Indeed, its dysfunction is related to a neurodegenerative disease called Friedreich’s ataxia (12). Frataxin is also capable of binding different divalent and trivalent cations, whose recognition sites have been mapped (13). Furthermore, frataxin is involved in donating iron to ferrochelatease via direct interaction through an extended binding site involving some of the residues implicated in metal binding (14).We have previously shown that frataxin folds via a complex mechanism, which we described through a broad free energy barrier (15). This feature, which has been associated with frustration (16), allows the experimental characterization of both the early and late events of folding (16–19). In this work we explored the mechanistic details of the folding reaction of frataxin at residue-level resolution. This result was achieved by characterizing the structures of both the early and late events of folding using Φ-value analysis (20) and restrained molecular dynamics simulations (21). By analyzing the structures of the different states along the folding process we found an unexpected number of nonnative interactions that slow down folding and superpose with the highly frustrated regions, as detected by the frustratometer server (22). The nonnative regions, which display peculiar Φ values, either negative or greater than unity, were predicted on the basis of the transition state structures determined from the Φ values, and subsequently confirmed by a second round of amino acid substitutions rationally designed to probe misfolded regions along the folding pathway.The characterization of the folding pathway of frataxin and of its misfolded elements enables us to discuss the competition between folding and function and its consequences for misfolding and aggregation.     

Tn2009, a Tn916-like element containing mef(E) in Streptococcus pneumoniae

The association between the macrolide efflux gene mef(E) and the tet(M) gene was studied in two clinical strains of Streptococcus pneumoniae that belonged to serotypes 19F and 6A, respectively, and that were resistant to both tetracycline and erythromycin. The mef(E)-carrying element mega (macrolide efflux genetic assembly; 5,511 bp) was found to be inserted into a Tn916-like genetic element present in the chromosomes of the two pneumococcal strains. In both strains, mega was integrated at the same site, an open reading frame identical to orf6 of Tn916. The new composite element, Tn2009, was about 23.5 kb and, with the exception of the tet(M)-coding sequence, appeared to be identical in both strains. By sequencing of the junction fragments of Tn2009 at the site of insertion into the chromosome, it was possible to show that (i) the insertion site was identical in the two clinical strains and (ii) the integration of Tn2009 caused a 9.5 kb-deletion in the pneumococcal chromosome. It was not possible to detect the conjugal transfer of Tn2009 to a recipient pneumococcal strain; however, transfer of the whole element by transformation was shown to occur. It is possible to hypothesize that Tn2009 relies on transformation for its spread among clinical strains of S. pneumoniae.     

The mef(E)-carrying genetic element (mega) of Streptococcus pneumoniae: insertion sites and association with other genetic elements

The structure of the macrolide efflux genetic assembly (mega) element, its genomic locations, and its association with other resistance determinants and genetic elements were investigated in 16 Streptococcus pneumoniae isolates carrying mef(E), of which 1 isolate also carried tet(M) and 4 isolates also carried tet(M) and erm(B). All isolates carried a mega element of similar size and structure that included the operon mef(E)-msr(D) encoding the efflux transport system. Among tetracycline-susceptible isolates, six different integration sites were identified, five of which were recognized inside open reading frames present in the R6 genome. In the five isolates also carrying tet(M), mega was inserted in different genetic contexts. In one isolate, it was part of previously described Tn916-like element Tn2009. In another isolate, mega was inserted in a transposon similar to Tn2009 that also included an erm(B) element. This new composite transposon was designated Tn2010. Neither Tn2009 nor Tn2010 could be transferred by conjugation to pneumococcal or enterococcal recipients. In the three isolates in which mega was not physically linked with tet(M), this gene was associated with erm(B) in transposon Tn3872, a Tn916-like element. Homologies between the chromosomal insertions of these composite transposons and sequences of multidrug-resistant pneumococcal genomes in the databases indicate the presence of preferential sites for the integration of composite Tn916-like elements carrying multiple resistance determinants in S. pneumoniae.     

Automatic measurement and visualization of focal femoral cartilage thickness in stress-based regions of interest using three-dimensional knee models

Purpose

Thinning of cartilage is a common manifestation of osteoarthritis. This study addresses the need of measuring the focal femoral cartilage thickness at the weight- bearing regions of the knee by developing a reproducible and automatic method from MR images.

Methods

3D models derived from semiautomatic MR image segmentations were used in this study. Two different methods were examined for identifying the mechanical loading of the knee articulation. The first was based on a generic weight-bearing regions definition, derived from gait characteristics and cadaver studies. The second used a physically based simulation to identify the patient-specific stress distribution of the femoral cartilage, taking into account the forces and movements of the knee. For this purpose, four different scenarios were defined in our 3D finite element (FE) simulations. The radial method was used to calculate the cartilage thickness in stress-based regions of interest, and a study was performed to validate the accuracy and suitability of the radial thickness measurements.

Results

Detailed focal maps using our simulation data and regional measurements of cartilage thickness are given. We present the outcome of the different simulation scenarios and discuss how the internal/external rotations of the knee alter the overall stress distribution and affect the shape and size of the calculated weight-bearing areas. The use of FE simulations allows for a patient-specific calculation of the focal cartilage thickness.

Conclusion

It is important to assess the quantification of focal knee cartilage morphology to monitor the progression of joint diseases or related treatments. When this assessment is based on MR images, accurate and robust tools are required. In this paper, we presented a set of techniques and methodologies in order to accomplish this goal and move toward personalized medicine.