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Aim: This study aims to examine the composition of lining and masticatory mucosa at the pre- and post-soft tissue augmentation procedures with a volume-stable cross-linking collagen matrix (VCMX) in humans., Materials and Methods: In 12 patients, single implant sites were augmented with a VCMX. Biopsies were obtained including masticatory (MM) and lining (LM) mucosa before augmentation and at 12 weeks post-augmentation procedures. Rete pegs density (RPD), length (RPL), and blood vessel density (BVD) were histomorphometrically analyzed at both time points. Picrosirius red staining under polarized light microscopy was used to evaluate collagen fiber organization. The effects of time and tissue type were evaluated by ANOVA with repeated measures., Results: Both MM and LM areas demonstrated an increase in mean RPL following augmentation, 382.6 µm ± 95.1 vs. 290.5 µm ± 79.3 and 335.6 µm ± 94.2 vs. 292.9 µm ± 77.0, respectively (p < .05). There was a significant difference in the numbers of RP per 1 mm length (RPD) between the MM (9.2 ± 1.7) and LM (6.1 ± 2.8) mucosa but not between the pre- and post-VCMX augmentation time points. The mean BVD in the LM was greater than in the MM (5.5 ± 2.4 and 6.3 ± 2.4 vs. 3.4 ± 3.3 and 3.7 ± 1.8, respectively, p < .05) but not between time points. The collagen fiber arrangements pre- and post-augmentation were not significantly different., Conclusion: Augmentation with VCMX did not alter the composition of lining and masticatory mucosa at implant sites., Clinical Relevance: A thick soft tissue phenotype around the implant neck is an important factor to maintain peri-implant health. A non-autogenous cross-linking collagen matrix is proposed as an alternate graft substitute in soft tissue augmentation procedures in order to improve implant soft tissue phenotype., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: The aim of the present study was to assess macroscopically the time-related dimensional pattern of excisional palatal mucoperiosteal wound closure in rats, concomitantly with microscopic analysis of the density of inflammatory infiltrate and myofibroblasts., Materials and Methods: Excisional palatal wounds, 4.2 mm in diameter, were made in twenty-one 2-month-old male Wistar rats. The total area and anteroposterior/laterolateral dimensions of the wounds were measured macroscopically at 1, 2, and 3 weeks post-operatively. In addition, histomorphometry was used for assessment of the intensity of inflammation and density of myofibroblasts in the wound area., Results: A significant decrease was found in the total area and anteroposterior but not the laterolateral dimension of the wounds during the 2nd week. These changes were less prominent in the 3rd week. Three weeks post-operatively, the density of inflammatory infiltrate remained high in the central part of the wound concomitant with a significant increase in the number of myofibroblasts., Conclusions: We concluded that the second week was the most significant in wound closure, with wound contraction first occurring in an anteroposterior plane followed by the laterolateral plane. The increased inflammatory reaction and changes in the density of myofibroblasts may explain the macroscopic decrease in wound dimensions in a time-related manner., Clinical Relevance: These findings emphasize the importance of the amount of soft tissue left at surgery, and suggest that the most appropriate time for the use of healing promoters would be the second post-operative week.

Purpose: To determine the Fourier-transform infrared (FTIR) spectra of salivary exosomes from oral cancer (OC) patients and healthy individuals (HI) and to assess its diagnostic potential using computational-aided models., Methods: Whole saliva samples were collected from 21 OC patients and 13 HI. Exosomes were pelleted using differential centrifugation (12,000g, 120,000g). The mid-infrared (IR) absorbance spectra (900-5000 cm - 1 range) were measured using MIR8025 Oriel Fourier-transform IR equipped with a PIKE MIRacle ZnSe attenuated total reflectance attachment. Machine learning techniques, utilized to build discrimination models for the absorbance data of OC and HI, included the principal component analysis-linear discriminant analysis (PCA-LDA) and support vector machine (SVM) classification. Sensitivity, specificity and the area under the receiver operating characteristic curve were calculated., Results: IR spectra of OC were consistently different from HI at 1072 cm - 1 (nucleic acids), 2924 cm - 1 and 2854 cm - 1 (membranous lipids), and 1543 cm - 1 (transmembrane proteins). The PCA-LDA discrimination model correctly classified the samples with a sensitivity of 100%, specificity of 89% and accuracy of 95%, and the SVM showed a training accuracy of 100% and a cross-validation accuracy of 89%., Conclusion: We showed the specific IR spectral signature for OC salivary exosomes, which was accurately differentiated from HI exosomes based on detecting subtle changes in the conformations of proteins, lipids and nucleic acids using optimized artificial neural networks with small data sets. This non-invasive method should be further investigated for diagnosis of oral cancer at its very early stages or in oral lesions with potential for malignant transformation.

Objectives: Lipoid proteinosis (LP) is a rare autosomal recessive disorder characterized by deposits of hyaline material within skin and mucous membranes of the upper aerodigestive tract, especially the vocal cords. We aimed to investigate possible associations between oral LP (oLP) manifestations and demographic data and extra-oral lesions., Material and Methods: Cases of oLP were collected following a systematic search of Medline's PubMed and Google Scholar (1948-2014). We added four new cases. Demographic data, consanguineous marriage status, oral lesion site(s), and related symptoms were analyzed for potential associations., Results: A total of 137 patients with oLP lesions were analyzed. Parental consanguinity status was known for 52 patients, and the parents were not related in 38 (73%) of them. The tongue was the most commonly affected oral site (68%), and it was associated with significantly more affected family members (P = 0.002). The palate and gingiva were the least involved sites (25 and 6%, respectively): the former had a tendency to be affected in younger patients and the latter in older ones. Patients with palatal and labial lesions had significantly less skin scarring (P < 0.001 and P = 0.002, respectively)., Conclusions: Extra-oral manifestations are easily recognizable and they can lead to early and accurate diagnosis of LP. In spite of early voice manifestations, diagnosis of LP might be obvious only later in life and usually sought due to presence of oral lesions., Clinical Relevance: The diagnosis of oLP with obscure extra-oral signs is challenging, with dental surgeons playing a key role in its establishment.

Purpose: Oral cancer (OC) patients are at high risk to develop recurrent disease or secondary primary cancers with no available biomarkers to detect these events until a visible lesion is readily present and diagnosed by biopsy. Exosomes secreted by cancer cells are involved in tumor growth, invasion and metastasis. We aimed to determine morphological and molecular differences between oral fluid (OF)-derived exosomes of OC patients and those isolated from healthy individuals (HI)., Methods: OF from OC patients (n = 36) and HI (n = 25) was initially assessed by nanoparticle tracking analysis (NTA). Following ultracentrifugation, exosomal pellets of OC patients and HI were morphologically examined by transmission electron microscopy and atomic force microscopy (AFM). Enzyme-linked immunosorbent assay (ELISA) and western blotting (WB) were used to analyze the expression of exosomal markers--CD9, CD81 and CD63., Results: NTA showed that OC samples of OF had a significantly higher concentration of nanoparticles/ml (p = 0.01) and modal nanoparticle size (p = 0.002) compared to HI. The difference in size was structurally highlighted by AFM three-dimensional images applied on exosomal pellets. ELISA and WB showed differential expression of exosomal markers in OC exosomes compared to HI: lower expression of CD81 and CD9 in contrast to a higher expression of CD63 (~53 kDa)., Conclusions: OF-derived exosomes from OC patients differ both morphologically and molecularly from exosomes present in HI. This study is a baseline that provides a starting point for finding exosomal biomarkers for early detection of malignant changes in high-risk patients without overt clinical signs/lesions.

Objectives: We sought to investigate the expression of cells with immunosuppressive/protumorigenic phenotypes in oral lichen planus (OLP), such as M2-tumor-associated macrophages (TAM2), myeloid-derived suppressive cells (MDSCs), and regulatory T cells (Tregs) in association with clinical parameters., Materials and Methods: Cases of hyperkeratotic (HK)-OLP (n = 23) and erosive (E)-OLP (n = 26) were immunohistochemically stained to determine the percentages of CD163-TAM2, CD80-MDSCs, and FOXP3-Tregs of proinflammatory CD121a-Th17, CD4 and CD8 lymphocytes, and of cells positive for nuclear factor kappa B (NF-κB) and transforming growth factor beta. Clinical parameters included symptoms, treatment approach, treatment response, and others., Results: The inflammatory infiltrate in HK-OLP and E-OLP contained immunosuppressive cells; however, their pattern of expression was compatible with a proinflammatory response [membranous CD163-TAM2 staining (not extracellular), CD80+ lymphocytes (not macrophages), and a few Tregs]. The presence of CD4+, CD8+, and CD121a+ T lymphocytes was extensive. TAM2 were more frequent in E-OLP than in HK-OLP (P = 0.017). A higher frequency of CD80+ lymphocytes was associated with partial to no response to treatment (P = 0.028). Nuclear expression of NF-κB in the inflammatory cells was absent., Conclusions: The pattern of expression of the immunosuppressive cells, together with numerous CD4+, CD8+, and Th17-CD121a+ lymphocytes, suggest an extensive proinflammatory response rather than an immunosuppressive/protumorigenic response., Clinical Relevance: The frequency of selective types of inflammatory cells calls for individual profile analyses of inflammatory infiltrates and individually adjusted treatment.

Purpose: To apply the Brandwein-Gensler et al.'s histopathologic risk score (RS) system and to evaluate its impact on locoregional recurrence and overall survival in a series of cases of oral tongue cancer, along with variables of patient age and margin status., Methods: Sections of the resection specimens (N = 50) were submitted to a RS assignment of three components: the worst pattern of invasion, lymphocytic infiltration and perineural invasion. Risk scores of 0-2 were classified as low-to-intermediate and RSs > or = 3 were classified as high with respect to recurrence and survival. Margins were considered as "clean" if the tumor was > or = 5 mm away from them, otherwise they were defined as "positive". Patients < or = 60 years were considered "young" and those >60 years "old". Kaplan-Meier survival analysis with univariate and Cox multivariate regression model with stepwise forward selection tests were used., Results: Univariate analysis showed that locoregional recurrence was negatively influenced by high RSs (P = 0.011), "young" age (P = 0.027) and positive margins (P = 0.027). Multivariate analysis revealed that the risk of recurrence was increased by high RSs (hazard ratio 11.14; P = 0.022) and "young" age (hazard ratio 3.41; P = 0.022). "Young" patients with high RSs had a higher frequency of recurrence rate compared to "young" patients with low-to-intermediate scores (P = 0.008) and "old" patients with low-to-intermediate and high RSs (P = 0.012 and P = 0.011, respectively)., Conclusions: The histopathologic RS can serve to identify a subgroup of patients <60 years who have a high recurrence rate of oral tongue cancer, irrespective of the margin status.