Purpose To evaluate by computerized tomography the long-term volume resorption of autogenous corticocancellous grafted bone harvested from the ilium and used in an alveolar augmentation procedure ...followed by endosseous dental implant placement. Patients and Methods Eleven maxillary grafts (8 positioned horizontally) and 13 mandibular grafts (10 positioned vertically) were placed in 16 patients. Using software programs, pre- and postsurgical computerized tomographic scans were used to compare volumes of grafts over time (up to 6 yr) to determine the annual percentage of remaining bone and the overall percentage of bone resorption that could be expected. Yearly measurements of volumes and percentages of remaining bone were then compared statistically. Results At the 6-year survey for blocks grafted in the mandible, an average resorption rate of 87% was obtained; for maxillary grafts at the same survey, complete resorption of the grafts (mean, 105.5%) was recorded. In general, bone resorption appeared slow, except for that recorded in the first 2 years of healing, the only period in which statistical comparisons among all time points showed significant differences for all variables. Conclusions Volumetric measurements of the grafts and their related percentages of remaining bone attested to a progressive and unavoidable bone resorption of almost all the grafted bone in the maxilla and mandible. Although the present data were from a heterogenous group of defects treated with horizontal and vertical procedures, clinicians, when performing alveolar bone augmentation with an autogenous hip bone, should aim at titanium dental implant osseointegration, not only in the augmented bone but also in the native bone below the graft.
Periodontitis has been associated with an increased risk of and mortality associated with human colorectal cancer (CRC). Current evidence attributes such an association to the direct and indirect ...effects of virulence factors belonging to periodontal pathogens, to inflammatory mediators and to genetic factors. The aims of the study were to assess the existence of a genetic linkage between periodontitis and human CRC, to identify genes considered predominant in such a linkage, thus named leader genes, and to determine pathogenic mechanisms related to the products of leader genes. Genes linking periodontitis and CRC were identified and classified in order of predominance, through an experimental investigation, performed via computer simulation, employing the leader gene approach. Pathogenic mechanisms relating to leader genes were determined through cross-search databases. Of the 83 genes linking periodontitis and CRC, 12 were classified as leader genes and were pathogenically implicated in cell cycle regulation and in the immune-inflammatory response. The current results, obtained via computer simulation and requiring further validation, support the existence of a genetic linkage between periodontitis and CRC. Cell cycle dysregulation and the alteration of the immuno-inflammatory response constitute the pathogenic mechanisms related to the products of leader genes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Uterine leiomyomas are benign tumors in the smooth muscle layer of the uterus. The most common histological type is the “usual leiomyoma”, characterized by overexpression of ECM proteins, whereas the ...“cellular type” has higher cellular content. Our objective is to investigate the involvement of inflammatory and reparative processes in leiomyoma pathobiology. Using a morphological approach, we investigate the presence of inflammatory cells. Next, we determine the localization of the ECM, the presence/absence of fibrotic cells via α-sma and desmin and the immunohistochemical profile of the mesenchymal cells with respect to CD34. Finally, we explore the effect of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-15, GM-CSF and IFN-γ) on pro-fibrotic factor activin A mRNA expression in vitro. Higher numbers of macrophages were found inside and close to leiomyomas as compared to the more distant myometrium. Cellular leiomyomas showed more macrophages and mast cells than the “usual type”. Inside the fibroid tissue, we found cells positive for α-sma, but negative for desmin and a large amount of collagen surrounding the nodule, suggestive of myofibroblasts producing ECM. In the myometrium and leiomyomas of the “usual type”, we identified numerous CD34+ fibroblasts, which are known to give rise to myofibroblasts upon loss of CD34 expression. In leiomyomas of the “cellular type”, stromal fibroblasts were CD34-negative. Finally, we found that TNF-α increased activin A mRNA in myometrial and leiomyoma cells. In conclusion, this study demonstrates the presence of inflammatory cells in uterine leiomyomas, which may contribute to excessive ECM production, tissue remodeling and leiomyoma growth.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Context: Fine-needle aspiration cytology (FNAC) is the gold standard for the differential diagnosis of thyroid nodules but has the limitation of inadequate sampling or indeterminate lesions.
...Objective: We aimed to verify whether search of thyroid cancer-associated protooncogene mutations in cytological samples may improve the diagnostic accuracy of FNAC.
Study Design: One hundred seventy-four consecutive patients undergoing thyroid surgery were submitted to FNAC (on 235 thyroid nodules) that was used for cytology and molecular analysis of BRAF, RAS, RET, TRK, and PPRγ mutations. At surgery these nodules were sampled to perform the same molecular testing.
Results: Mutations were found in 67 of 235 (28.5%) cytological samples. Of the 67 mutated samples, 23 (34.3%) were mutated by RAS, 33 (49.3%) by BRAF, and 11 (16.4%) by RET/PTC. In 88.2% of the cases, the mutation was confirmed in tissue sample. The presence of mutations at cytology was associated with cancer 91.1% of the times and follicular adenoma 8.9% of the time. BRAF or RET/PTC mutations were always associated with cancer, whereas RAS mutations were mainly associated with cancer (74%) but also follicular adenoma (26%). The diagnostic performance of molecular analysis was superior to that of traditional cytology, with better sensitivity and specificity, and the combination of the two techniques further contributed to improve the total accuracy (93.2%), compared with molecular analysis (90.2%) or traditional cytology (83.0%).
Conclusions: Our findings demonstrate that molecular analysis of cytological specimens is feasible and that its results in combination with cytology improves the diagnostic performance of traditional cytology.
Search of a complete panel of oncogene mutations in cytological specimens of thyroid nodules is feasible and improves the diagnostic performance of traditional cytology.
The glycoprotein CD93 has recently been recognized to play an important role in the regulation of the angiogenic process. Moreover, CD93 is highly expressed in the endothelial cells of tumor blood ...vessel and faintly expressed in the non-proliferating endothelium. Much evidence suggests that CD93 mediates adhesion in the endothelium. Here we identify Multimerin 2 (MMRN2), a pan-endothelial extracellular matrix protein, as a specific ligand for CD93. We found that CD93 and MMRN2 are co-expressed in the blood vessels of various human tumors. Moreover, disruption of the CD93-MMRN2 interaction reduced endothelial cell adhesion and migration, making the interaction of CD93 with MMRN2 an ideal target to block pathological angiogenesis. Model structures and docking studies served to envisage the region of CD93 and MMRN2 involved in the interaction. Site-directed mutagenesis identified different residue hotspots either directly or indirectly involved in the binding. We propose a molecular model in which the coiled-coil domain of MMRN2 is engaged by F238 of CD93. Altogether, these studies identify the key interaction surfaces of the CD93-MMRN2 complex and provide a framework for exploring how to inhibit angiogenesis by hindering the CD93-MMRN2 interaction.
•CD93 and MMRN2 are molecular partners on the EC surface.•CD93 and MMRN2 are co-expressed in the blood vessels of various tumors.•The blockage of the CD93-MMRN2 interaction using a CD93 protein fragment inhibits in vitro angiogenesis.•A molecular model of the CD93-MMRN2 protein complex is described.•An amino acid residue of CD93 is essential for interaction with MMRN2 and for EC migration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
After tooth extraction, the alveolar bone tends to shrink in volume, especially on the vestibular side. The role of myofibroblasts in bone remodeling has not been sufficiently investigated. The aim ...of the present study was to explore the gene expression related to myofibroblasts presence and activity during a 90-day healing period after tooth extraction. The study included 36 rabbits, and a single tooth extraction was performed on each rabbit. The extractive sockets were randomly distributed to natural healing or to scarification of the wound. The sacrifices were staggered in such a manner that animals contributed with sockets representing 2, 7, 15, 30, 60, and 90 days of healing. Nanostring technology was used to evaluate the expression of a wide panel consisting in 148 genes related to the activation, induction, and suppression of myofibroblasts, socket microenvironment, and autophagy. We found that the expression profile of this custom panel was time-related. The post-extractive socket was subjected to significant gene expression changes after 15 days: the genes involved in the induction of myofibroblasts were up-regulated in the first 15-day period and down-regulated during the rest of the follow-up. The study suggested that myofibroblasts play a major role in the immediate 15-day period following tooth extraction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The present retrospective analysis aimed to compare two different single tooth extraction surgical approaches in both premolar and molar areas: less traumatic magneto-electrical versus conventional ...tooth extraction in minimizing the edentulous ridge volume loss.
In the present retrospective control trial, 48 patients who underwent one-tooth extraction, were allocated either to control (28 sites treated with conventional tooth extraction procedures) or test group (20 subjects treated with less traumatic tooth extraction procedures by tooth sectioning and magnetoelectric roots subluxation). Intraoperatively (during tooth extraction surgery just after the subsequent filling of the alveolar socket with the sterile fast re-absorbable gelatin sponge), and then four months later, contours of the sockets were acquired through a laser intra-oral scanner. The digitally superimposed models were converted to dicom (Digital Imaging and Communications in Medicine) format first, then volumetric and area evaluations were performed with a DentaScan tool package. Non-parametric tests were applied with a level of significance set at
< 0.01.
significant reductions of anatomical features were observed four months later in all the groups (
-values < 0.001) with volume losses leading to a final alveolar ridge volume of 0.87 ± 0.34 cm
for atraumatic extractions and 0.66 ± 0.19 cm
for conventional extractions. No significant differences were registered for outcomes related to the basal surface variables. When just molar tooth were considered, the outcomes relating to volume loss between baseline and four months (ΔV) and its percentage (ΔV%) showed a better behavior in the less traumatic procedure (ΔV = -0.30 ± 0.10 cm
and ΔV% = -22.3 ± 8.4%) compared to the conventional extractions (ΔV = -0.59 ± 0.10 cm
and ΔV% = -44.3 ± 5.8%) with
-values < 0.0001.
at four months, the less traumatic tooth extraction procedures by tooth sectioning and magnetoelectric root subluxation seemed to be able to better preserve the volume of the alveolar crest (reduction close to 22% with less traumatic extraction in molar sites) when compared to subjects treated with the conventional tooth extraction techniques.
to develop a clinical approach to evaluating osteointegration around bone implants and try to determining which was the correct time of implant loading in different edentulous indications, that is, ...either properly positioned implants or implants “at risk”, generally referred to as implants having increased probability of failure (namely those for which primary stability had been achieved via a time-consuming surgery).
Several implant-supported rehabilitation strategies, with or without bone augmentation procedures, were performed in the upper and lower arches:•dental implant placed in native bone;•dental implant placed in edentulous alveolar ridge with insufficient bone volume and undergone augmentation with split bone block technique;•dental implant placed in the posterior maxillary area with extreme hyperpneumatized of the maxillary sinus (3 mm or less of residual bone height) and underwent sinus lifting procedure with lateral approach.
From 2 to 5 months following implant placement, the prosthetic restorations were performed.
A resonance frequency analyzer allowed clinicians to measure intraoperative and postoperative implant stability, then the values of the implant stability quotient, ISQ, ranging from 0 to 100, were registered. ISQs were ranked into 3 levels: Green (ISQ ≥ 70), Yellow (60 ≤ ISQ < 70), and Red (ISQ < 60). Groups were subjected to Pearson's χ2 analysis, with YATES correction when necessary, with a significance level of 0.05.
A total of 213 implants had been included. When the distribution of normalized values of ISQ registered for implants inserted in native bone and loaded at 2-3 months (5 Red, 19 Yellow, and 51 Green) was compared to that of native implants loaded after 4-5 months (4 Red, 20 Yellow, and 11 Green), a significative difference was found (p-value = 0.0037). At the time of loading, significance was lost. Significant clinical improvements on the distribution of normalized values of ISQ were apparent for both the implants placed in pristine and those placed in lifted sinuses; no significant differences were registered between the two groups.
At the loading time, implants considered to be at risk behaved similarly to the native sites for which the overall prosthetic workflow took about few; results confirmed that the mandibular implants appeared to have higher stabilities when compared to maxillary implants at both the intraoperative and the postoperative surveys.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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