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Bullous pemphigoid (BP) has been repeatedly reported to occur following exposure to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study analyzes the molecular mimicry between the 180 kDa bullous pemphigoid antigen 2 (BP180) and the SARS-CoV-2 proteome to further our understanding of the molecular link between the BP and the SARS-CoV-2 infection. Results indicate a high degree of molecular mimicry between BP180, SARS-CoV-2, hCoV-229E and hCoV-NL63.

This paper covers genetic and biochemical aspects of mitochondrial bioenergetics dysfunction in hereditary neurological disorders associated with complex I defects. Three types of hereditary complex I dysfunction are dealt with: (i) homozygous mutations in the nuclear genes NDUFS1 and NDUFS4 of complex I, associated with mitochondrial encephalopathy; (ii) a recessive hereditary epileptic neurological disorder associated with enhanced proteolytic degradation of complex I; (iii) homoplasmic mutations in the ND5 and ND6 mitochondrial genes of the complex, cohexistent with mutation in the nuclear PINK1 gene in familial Parkinsonism. The genetic and biochemical data examined highlight different mechanisms by which mitochondrial bioenergetics is altered in these hereditary defects of complex I. This knowledge, besides clarifying molecular aspects of the pathogenesis of hereditary diseases, can also provide hints for understanding the involvement of complex I in sporadic neurological disorders and aging, as well as for developing therapeutical strategies.

The aim of this study was to perform a retrospective analysis of 52 cases of odontoma treated at the Department of Dentistry and Surgery, University of Bari, in the period 1971-2005.The odontogenic tumors were diagnosed as complex or compound odontoma following histological analysis and clinical radiological examination, and applying the 2005 WHO classification. The data analysis was conducted by considering the following factors: gender, age, site of the lesion, association with impacted teeth, aplasia, presence of supernumerary teeth as well as preoperative diagnosis by panoramic and periapical radiographs. Biopsy tissue samples were conventionally processed for histopathologic paraffin embedding and then were observed by optical microscopy and subsequently by confocal laser scanning microscopy (CLSM) in autofluorescence.Thirty specimens (57.6%) were from females and 22 (42.3%) were from males patients. The patients' age ranged from 5 to 75 years. Fifty-one percent of the specimens were excised from the mandible. In the maxilla, the most common location for odontomas was the anterior region. Most odontomas were associated with impacted teeth and only in one case there was an odontoma instead of a permanent tooth.Odontomas are considered hamartomatous malformations whose diagnosis is generally formulated by routinary radiographic examination. The CLSM analysis could help in diagnosis and histopathological analysis showing well-defined follicular area entrapped in hard tissues and pointing out ghost cells, otherwise not identifiable by traditional microscopy.

Traumatic ulcerative granuloma with stromal eosinophilia is an ulcerated oral lesion which pathogenesis is still unclear. Clinically, this disease is characterized by the presence of chronic ulcerative lesions with elevated and indurated borders in the oral mucosa. It usually develops rapidly and persists for several weeks or months, it presents mainly on the tongue but other areas such as gingival, cheek and vestibular mucosa may also be involved. We report three cases showing their clinical, histological and immunohistochemical analysis. In this study the authors underline the importance of a correct differential diagnosis and monitoring of these patients in order to prevent the development of possible serious complications.

International audience; BACKGROUND: A fixed-dose regimen of rivaroxaban, an oral factor Xa inhibitor, has been shown to be as effective as standard anticoagulant therapy for the treatment of deep-vein thrombosis, without the need for laboratory monitoring. This approach may also simplify the treatment of pulmonary embolism. METHODS: In a randomized, open-label, event-driven, noninferiority trial involving 4832 patients who had acute symptomatic pulmonary embolism with or without deep-vein thrombosis, we compared rivaroxaban (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with standard therapy with enoxaparin followed by an adjusted-dose vitamin K antagonist for 3, 6, or 12 months. The primary efficacy outcome was symptomatic recurrent venous thromboembolism. The principal safety outcome was major or clinically relevant nonmajor bleeding. RESULTS: Rivaroxaban was noninferior to standard therapy (noninferiority margin, 2.0; P=0.003) for the primary efficacy outcome, with 50 events in the rivaroxaban group (2.1%) versus 44 events in the standard-therapy group (1.8%) (hazard ratio, 1.12; 95% confidence interval [CI], 0.75 to 1.68). The principal safety outcome occurred in 10.3% of patients in the rivaroxaban group and 11.4% of those in the standard-therapy group (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding was observed in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). Rates of other adverse events were similar in the two groups. CONCLUSIONS: A fixed-dose regimen of rivaroxaban alone was noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and had a potentially improved benefit-risk profile. (Funded by Bayer HealthCare and Janssen Pharmaceuticals; EINSTEIN-PE ClinicalTrials.gov number, NCT00439777.).

El fibrolipoma es una neoplasia de origen mesenquimal, rara en la cavidad oral, representando el 1% de todos los tumores benignos orales. Es una variante histológica del lipoma simple, que normalmente se manifiesta a nivel de la mucosa oral, suelo de la boca, lengua y labios. La etiología suele ser traumática cuando afecta localizaciones extraorales, mientras se considera idiopática al manifestarse a nivel bucal. En este artículo se presenta un raro caso de fibrolipoma de mejilla, y se discuten los aspectos diagnósticos, histo-patológicos y de tratamiento de acuerdo a la literatura. Lipomas are common soft tissue mesenchymal neoplasms, rare in the oral cavity, representing 1% of all benign oral tumors. Fibrolipoma is a histological variant of the classic lipoma which normally affects buccal mucosa, floor of the mouth, tongue and lips. In this article is presented a rare case of fibrolipoma of the cheek and are discussed all the aspects of diagnosis, histology and surgical treatment, according to literature data.

El síndrome de Rendu-Osler-Weber, también conocido como Telangiectasia Hemorrágica Hereditaria, es un desorden vascular cuya prevalencia se estima que afecta a uno de cada 5-8.000 individuos. Se trata de una alteración vascular displásica multisistémica de carácter autosómico dominante, asociada a dos genes, HHT1 y HHT2, que determinan mutaciones en el gen endoglina (ENG), localizado en el cromosoma 9, y por mutaciones en el gen ALK1, localizado en el cromosoma 12. El 95% de los afectados presentan epitaxis recurrentes, con edad media de comienzo a los 12 años e incremento progresivo del sangrado nasal en frecuencia y severidad. Generalmente se presenta asociado a malformaciones arteriovenosas pulmonares y/o múltiples telangiectasias en sistema gastrointestinal, manos, cara, cavidad oral y afectación de otras vísceras. El diagnóstico inicial de HHT continúa basándose en la presencia de signos clínicos compatibles junto con la historia familiar. Para el diagnóstico molecular es necesario secuenciar las regiones codificantes completas de los genes ALK1 y ENG. El test genético no es positivo en el 100% de los pacientes con diagnóstico clínico de HHT, siendo posible no encontrar en un mismo grupo familiar la mutación común. Se revisa la literatura y se presentan dos casos con manifestaciones orales en lengua y labio inferior, sin otras lesiones sistémicas asociadas, tratada en nuestro departamento por problemas odontológicos. Rendu-Osler-Weber syndrome, also known as __Hereditary Hemorrhagic Telangiectasia (HHT), is a vascular disorder with a prevalence estimated in one in 5-8.000 individuals. It is a dominant autosomic transmission determining multisystemic vascular dysplasia, which has been mapped to two genes, HHT1 and HHT2, determined by mutations of the endoglin (ENG) gene, localized to the chromosome 9, and by mutations of the activin receptorlike kinase 1 (ALK1) gene, localized on the chromosome 12. The 95% of affected present recurrent epistaxis, with a mean age of first event at about 12 years, generally the nosebleed frequency and severity increase with age and usually it is associated with pulmonary AVM and/or multiple telangiectases of gastrointestinal apparatus, of the hands, face, and oral cavity and others visceral involvement. The first diagnosis of HHT is still based on the presence of clinical signs and family history; for the molecular diagnosis of HHT is necessary sequencing the entire coding regions of the ALK1 and ENG genes. The genetic test is positive not in the 100% of all patients with clinical diagnosis of HHT, but it is also possible not find in the same family group the common mutation. We review the litterature and report 2 cases with oral manifestation, on the tongue and on the inferior lip, without others systemic HHT lesions, treated in our Department for general odontoiatric problems.

Down syndrome (DS) is an autosomal disorder associated with mental and physical involvement. The typical craniofacial phenotype and the dental anomalies in DS subjects have been widely described, but a systematic report on the manifestations affecting the oral mucosae in children with DS is still lacking. This systematic review aimed to establish the prevalence of oral mucosal manifestations in children/young adults with DS. Pubmed, Web of Science, and Scopus were investigated in September 2020. Documents in English on DS children/young adults (up to 25 years) reporting oral mucosal findings were considered. Study quality was assessed with ROBIN-I. Of the 150 references retrieved, 14 studies were considered eligible. The risk of bias ranged from low to unclear. Fissured tongue appeared to increase with age and was more prevalent in DS children than in the general population. Lip fissures and cheilitis were heterogeneously reported. Candida spp. carriage with and without active candidiasis was more frequent in DS children/young adults than in controls. C. albicans was the most prevalent species. Few other oral mucosal conditions have been reported sporadically. The heterogeneity of the works revealed the need for more appropriate oral examination to intercept the oral manifestations of oral mucosa and prevent recurrent candidiasis.

Fibro-osseous lesions (FOL) represent a heterogeneous group of lesions that exhibit a variety of clinic-pathological features. Recently, based on the new World Health Organization classification system, these lesions were reclassified as follows: (1) fibrous dysplasia (FD), (2) osseous dysplasia, and (3) ossifying fibroma. Nevertheless, the nosologic placement of FOL may be problematic because of substantial overlap in the histopathological findings. In this study, we analyzed 10 cases of FD by both optical and confocal laser scanning microscopy, a research technique based on the laser light microscopic analysis of stained biological samples that allows improved tissue imaging and bidimensional pictures with high resolution at the cellular level to provide a better understanding of the diagnosis of this disease. Fibro-osseous lesions (FOL) represent a heterogeneous group of lesions that exhibit a variety of clinic-pathological features. Recently, based on the new World Health Organization classification system, these lesions were reclassified as follows: (1) fibrous dysplasia (FD), (2) osseous dysplasia, and (3) ossifying fibroma. Nevertheless, the nosologic placement of FOL may be problematic because of substantial overlap in the histopathological findings. In this study, we analyzed 10 cases of FD by both optical and confocal laser scanning microscopy, a research technique based on the laser light microscopic analysis of stained biological samples that allows improved tissue imaging and bidimensional pictures with high resolution at the cellular level to provide a better understanding of the diagnosis of this disease.

Lichen planus is an inflammatory mucocutaneous disorder. Skin, oral and genital mucosal surfaces, scalp, and nails can be affected. Its development is chronic, with a possible malignant degeneration. Spontaneous remission is rare. Although the etiology of oral lichen planus is still unclear, there is evidence that it is a complex immunologic disease mediated by cytotoxic cells directed against basilar keratinocytes and resulting in vacuolar degeneration and lysis of basal cells. In long-standing, atrophic and erosive forms, the treatment is usually aimed at relieving pain and may include immunosuppressive agents, especially corticosteroid, topical cyclosporin, or tacrolimus, topical and systemic retinoids. However, the use of these drugs may be accompanied by several side effects. For this reason clinicians, currently, have focused their attention to new biological agents which provide selective immunological results with less side effects than generic immunosupressants.

Liesegang rings are concentric noncellular lamellar structures, occasionally found in inflammatory tissues. They have been confused with various parasites, algas, calcification, and psammoma bodies. The authors examined Liesegang rings from oral inflammatory cysts by both optical and confocal laser scanning microscopy, and perfomed a three-dimensional reconstruction. These investigations indicate that Liesegang rings are composed of multiple birefringent concentric rings, resulting from a progressive deposition of organic substances, with an unclear pathogenesis.

Pulse granuloma is a rare benign entity considered to be a foreign-body reaction to vegetables particles. It occurs most frequently in the oral cavity of edentulous patients wearing a complete mobile denture, associated with impacted lower third molar or in postextractive alveolar sockets. The authors analyzed 2 cases by both optical and confocal laser scanning microscopy, a research technique based on laser light microscopic analysis of biological samples stained for fluorescence observation. CLSM allowed improved tissue imaging, bidimensional pictures with better resolution at cellular level, and, in particular, the possibility of a three-dimensional image reconstruction. In conclusion, this study reports the fine definition of pulse granuloma at microscopic level by CLSM and the results warrant the use of this technique for further analyses.

Objective The confocal laser scanning microscope represents an effective tool for studying biological samples stained for fluorescence observation. In this study we have used the confocal microscope to analyze ghost cells in calcifying cystic odontogenic tumors. Study design Specimens from 15 calcifying cystic odontogenic tumor cases were stained with hematoxylin and eosin, and scanned by a confocal laser scanning microscope to generate optically sectioned images. Results All of the analyzed samples presented autofluorescent cells that were identified as ghost cells. The degree of autofluorescence intensity was variable and may be a result of the presence of hard keratin. Conclusion The confocal laser scanning microscope may be of help in analyzing and defining the nature and extent of keratinization processes in calcifying cystic odontogenic tumor ghost cells.

PURPOSE:: Cellular populations of gingival crevicular fluid cytological analysis of integrated implants sites have been investigated by using sulcular cytological brushing, as a means of providing an objective and reproducible technique for monitoring periimplant tissue health. MATERIALS AND METHODS:: A total of 60 patients with osteointegrated implants bearing at least for 2 years were divided in 2 groups, A and B. Group A consisted of 30 subjects who presented scarce oral hygiene. In Group B, 30 subjects with a good oral hygiene were included. RESULTS:: Comparative analysis of the data obtained by sulcular microbrushing of the 2 groups put into evidence significative differences in the expression of the microbiological and the cytological parameters. CONCLUSION:: Clinical monitoring of parodontal and periimplant tissues makes use of several diagnostic tests ranging from clinical and radiological tests to biological assays. However, none of these techniques allows to evaluate periimplant tissue cytological status. This preliminary study suggested sulcular microbrushing might be a useful tool in the early diagnosis and in the micrological monitoring of peri-implantitis.

The so-called calcifying odontogenic cyst (COC) represents a heterogeneous group of lesions that exhibit a variety of clinico-pathologic features. It is an uncommon lesion and represents less than 2% of all odontogenic cysts and tumors. Recently, these lesions have been reclassified as calcifying cystic odontogenic tumors (CCOT), according to the new World Health Organization (WHO) classification. CCOT are frequently found in association with, or containing areas histologically identical to, various types of odontogenic tumors, such as complex/compound odontomas. This work analyzed clinical and histological data deriving from 13 patients affected by CCOT associated with odontomas. Moreover, a confocal laser scanning microscope (CLSM) analysis was undertaken to further a better understanding of the nature of this peculiar lesion.

Summary In order to define a practical method for a quantitative–qualitative analysis of dental hard tissue cells, we have studied cementocytes of human teeth using Confocal Laser Scanning Microscopy (CLSM), a research technique based on laser light microscopic analysis of biological samples stained for fluorescence observation. One thousand and eight hundred cementocyte images were analyzed. CLSM allowed improved tissue imaging, bi-dimensional pictures with better resolution at cellular level and, in particular, the possibility of a three-dimensional image reconstruction, thus providing a dynamic view of the cell under different situations. CLSM allowed a careful morphological observation and dimensional analysis of cementocytes at cellular resolution: cementocyte dimensional parameters like cell body without cell processes, cell dimensions with cell processes, and the number of cellular processes could be obtained. In conclusion, this study reports the fine definition of cementocytes at microscopic level by CSLM and the results warrant the use of this technique for further comparative analyses between normal and pathological cementocyte cells, e.g. cementum neoplasia and periodontal disease which still await a clear analytical description at cellular level.

Confocal laser scanning microscopy (CLSM) represents a recent acquisition in the study of biological samples stained for fluorescence observation. Particularly, this technique allows a bidimensional investigation of tissues and cells with the possibility to elaborate a three-dimensional model. The aim of this study is the use of this technique, as a complementary and not substitutive application of the histological examination, for the morphological and histopathological analysis in a case of mixed complex-composed odontoma. The analyzed specimen has been surgically removed in the superior frontal region in a 12 year-old boy and submitted to conventional histopathological analysis. The specimen, hematoxylin-eosin stained, has been subsequently submitted to confocal laser scanning microscopic analysis in autofluorescence by using a Nikons C1 system. This analysis has underlined not visible aspects in traditional optical microscopy, such as the mineralization of hard tissues and the morpho-structural organization of the cellular component. The presence of enamel and dentin may be observed in the different phases of odontogenesis with clear fluorescence gradients determined by the different mineralization degrees. Thus, the odontogenetic components appear strongly autofluorescent in the classical follicular configuration. Three-dimensional reconstruction is made possible by the acquisition of serial bidimensional images that are subsequently analysed by using a specific software device. This study shows the confocal laser scanning microscopy versatility in the analysis of odontogenic neoplasms with production of mineralized tissues.