Single ulcers on the tongue dorsum: differential diagnosis between paracoccidioidomycosis and squamous cell carcinoma.

BACKGROUND: Paracoccidioidomycosis (PCM) is the leading cause of death among systemic mycoses in Brazil. On the other hand, oral squamous cell carcinoma (OSCC) is the most prevalent malignant neoplasm of the mouth. Both lesions rarely affect the tongue dorsum and may share similar clinical characteristics. This study aimed to retrieve cases of single oral ulcers diagnosed as PCM or OSCC. MATERIAL AND METHODS: A cross-sectional retrospective study was conducted. All patients who had a single ulcer on dorsum of the tongue and confirmed diagnosis of PCM or OSCC were evaluated. RESULTS: A total of 9 patients (5 women and 4 men) were evaluated, 5 patients had OSCCs (mean age = 69,8 years old), and 4 patients PCM (mean age = 51 years old). Most of the lesions were infiltrated and indurated in the palpation exam. Duration ranged from 1 to 12 months (mean time of 5.2 months and 4.7 months for OSCC and PCM, respectively). OSCC was the main clinical diagnosis hypothesis. CONCLUSIONS: Although uncommon, PCM and OSCC should be considered as a diferential diagnosis hypothesis in infiltrated ulcers on the tongue dorsum. Iincisional biopsy is mandatory to confirm the diagnosis and indicate the appropriate treatment.

Investigating luxS gene expression in lactobacilli along lab-scale cocoa fermentations.

Previous metagenomic analyses have suggested that lactobacilli present potential for Quorum Sensing (QS) in cocoa fermentation, and in the present research, laboratory scale fermentations were carried out to monitor the expression of luxS, a universal marker of QS. For that, 96 h-fermentations were studied, as follows: F0 (non inoculated control), F1 (inoculated with yeasts, lactic acid bacteria, and acetic acid bacteria), F2 (inoculated with yeasts and acetic acid bacteria), F3 (inoculated with yeasts only). The parameters evaluated were: plate counting, quantification of key enzymes and analysis of volatile organic compounds associated with key sensory descriptors, using headspace gas chromatography-mass spectrometry (GC-MS). Furthermore, QS was estimated by the quantification of the expression of luxS genes by Reverse Transcriptase Real-Time PCR. The results demonstrated that microbial succession occurred in pilot scale fermentations, but no statistical differences for microbial enumeration and α-diversity index were observed among experiments and control. Moreover, it was not possible to make conclusive correlations of enzymatic profile and fermenting microbiota, likely due to the intrinsic activity of plant hydrolases. Regarding to the expression of luxS genes, in Lactiplantibacillus plantarum they were active along the fermentation, but for Limosilactobacillus fermentum, luxS was expressed only at early and middle phases. Correlation analysis of luxS expression and production of volatile metabolites evidenced a possible negative association of Lp. Plantarum with fermentation quality. In conclusion, these data corroborate former shotgun metagenomic analysis by demonstrating the expression of luxS by lactobacilli in pilot scale cocoa fermentation and evidence Lp. Plantarum is the main lactic acid bacteria related to its expression.

Lymphomas affecting the submandibular glands.

BACKGROUND: Lymphomas affecting the submandibular glands are very uncommon and few reports are currently available in the literature. Therefore, the aim of the current study is to describe the clinical and microscopic features of an original series of lymphomas affecting the submandibular glands. MATERIAL AND METHODS: The pathology files of two institutions were searched for lymphoma cases affecting the submandibular glands. The original hematoxylin and eosin, and immunohistochemical slides were revised by a pathologist for diagnosis confirmation following the revised 4th edition of the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Clinical data regarding age, sex, clinical manifestation, treatment, follow-up and status at last appointment were retrieved from the patients' medical charts. RESULTS: During the period investigated, 16 cases were included in the study. Females predominated (10:6) with a mean age of 57.8 years-old. Tumors usually presented as asymptomatic swellings. MALT lymphoma represented the most common subtype, followed by diffuse large B cell lymphoma and follicular lymphoma. Three patients died, one of them affected by plasmablastic lymphoma, one by DLBCL and one by MALT lymphoma. CONCLUSIONS: Low-grade B cell lymphomas predominate in the submandibular glands, but DLBCL and other subtypes may also be rarely diagnosed in this salivary gland.

Superficial mucoceles in cancer patients: a retrospective series from a Stomatology unit.

BACKGROUND: The aim of this study is to relate all the superficial mucoceles found in a cancer center, described the association with oncological conditions, and discuss its etiology and pathology that we found in the past few years. MATERIAL AND METHODS: Sixteen cases of superficial mucocele were retrieved from the patients' records of the Stomatology Department of the A. C. Camargo Cancer Center, São Paulo, Brazil, and demographic and clinical data were collected from electronic medical records. RESULTS: There were 16 patients, 8 patients were men and 8 women, with ages varying from 26 to 70 years old. Superficial mucoceles were observed in patients submitted to head and neck radiotherapy (n=6), graft versus host disease (n=4), one associated with oral mucositis related to allogenic bone marrow stem cells transplantation (n=1), systemic lupus (n=1), Sjögren's syndrome (n=1), oral lichenoid lesion associated with pembrolizumab (n=1) and no local or systemic inflammatory associated found (n=2). CONCLUSIONS: This study reports a series of superficial mucoceles from a single stomatology unit. Most patients had superficial mucoceles secondary to head and neck radiotherapy and graft versus host diseases. However, two patients (12.5%) had mucoceles related to systemic inflammatory conditions (Sjögren's Syndrome and Systemic Lupus).

Hearing Impairment and Incident Frailty in Later Life: The Health in Men Study (HIMS).

OBJECTIVES: This study is designed to determine if hearing loss is associated with increased risk of frailty in later life. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: We retrieved data of a community sample of men aged 70 years and above living in the metropolitan region of Perth, Western Australia. 3,285 participants who were free of frailty at the beginning of the study were followed for up to 17 years. Data were retrieved from the Health in Men Study (HIMS) and the Western Australian Data Linkage System (WADLS). MEASUREMENTS: Hearing loss was defined by self-report or by diagnosis recorded in the WADLS. Incident frailty was assessed using the Hospital Frailty Risk Score (HFRS). RESULTS: A total of 2,348 (71.5%) men developed frailty during follow up. The adjusted hazard ratio was 1.03 (95% CI: 0.95-1.12). The majority of the participants became frail by age 90 regardless of hearing condition. The time point where half of the group become frail was delayed by 14.4 months for men without hearing loss compared with hearing impaired men. CONCLUSIONS: Hearing loss is not associated with incident frailty in men aged 70 years or older when frailty was measured by HFRS. However, this statistically non-significant result could be due to the low sensitivity of study measures. Also, we found a trend that men with hearing loss were more likely to develop frailty compared with their normal-hearing peers, suggesting a potential association between hearing loss and frailty.

Effects of prenatal hypoxia-ischemia on male rat periaqueductal gray matter: Hyperalgesia, astrogliosis and nitrergic system impairment.

Prenatal hypoxic-ischemic insult (HI) may lead to a variety of neurological consequences that may persist throughout adulthood. In the most severe cases, HI is known to increase pain sensitivity which profoundly impacts quality of life. Periaqueductal gray matter (PAG) is a relevant region of the descending pain pathway and its function may be modulated by a complex network that includes nitrergic neurons and glial response, among other factors. Astrocytes, central players in pain modulation, are known to respond to HI by inducing hyperplasia, hypertrophy and increasing the number of their processes and the staining of glial fibrillary acidic protein (GFAP). In this work we investigated the effects of prenatal HI on touch and pain sensitivity, besides the distribution of the neuronal isoform of Nitric Oxide Synthase (nNOS) and GFAP in the PAG of young and adult male rats. At 18 days of gestation, rats had their uterine arteries clamped for 45 min (HI group). SHAM-operated animals were also generated (SHAM group). At post-natal day 30 (P30) or 90 (P90), the offspring was submitted to the behavioral tests of Von Frey and formalin or histological processing to perform immunohistochemistry for nNOS and GFAP. Although there was no significant difference between the groups concerning touch sensitivity, we observed an increase in pain sensitivity in HI P30 and HI P90. The number of nNOS + cells was reduced in HI adult animals in dlPAG and vlPAG. GFAP immunostaining was increased in HI P90 in dlPAG and dmPAG. Our results demonstrated for the first time an increase in pain sensitivity as a consequence of prenatal HI in an animal model. It reinforces the relevance of this model to mimic the effects of prenatal HI, as hyperalgesia.

Histomorphological evaluation, cell proliferation and endothelial immunostaining in oral and maxillofacial myofibroblastic lesions.

BACKGROUND: Myofibroblasts (MF) are mesenchymal cells with features of both fibroblasts and smooth muscle cells. Although these are usually reactive cells, they can lead to myofibroblastic tumors that may share clinical and histomorphological characteristics but with different prognosis. The aim of this study is to perform a histomorphological evaluation as well as to compare and evaluate two different cell proliferation immunomarkers and two endothelial markers in a group of oral and maxillofacial myofibroblastic lesions (MFL). MATERIAL AND METHODS: Cross-sectional and retrospective study. Demographic, clinical, histomorphological and immunohistochemical characteristics of 39 cases of MFL were analyzed. Immunohistochemical reactions were performed with the Ki67, MCM2, CD34 and CD105 antibodies. Kruskal-Wallis test and Spearman correlation analysis were used. RESULTS: Four cases of nodular fasciitis (NF), 18 myofibromas (My), 6 desmoplastic fibromas (DF), 7 inflammatory myofibroblastic tumors (IMT) and 4 myofibroblastic sarcomas (MFS) were studied. There were twenty women (51.2%); the median age was 13 [Q1-Q3: 8-24] years and most cases occurred in the mandible (48.7%). A statistically significant difference with MCM2 immunostaining (p=0.0221) was observed between the MFL; furthermore, a correlation between CD34 and CD105 immunostaining in NF (p <0.0001) and IMT (p=0.0408), between MCM2 and CD34 in IMT (p=0.0362) and between MCM2 and CD105 in MFS (p <0001) were found. CONCLUSIONS: MCM2 immunostaining could assess more clearly the cell growth fraction in MFL. The correlation between MCM2 and CD34 in IMT and between MCM2 and CD105 in MFS are indicative of the high activity of these lesions. These results emphasize the importance of the studied immunohistochemistry markers as possible tools for a better characterization of some of the MFL.

Angina bullosa haemorrhagica: A 14-year multi-institutional retrospective study from Brazil and literature review.

BACKGROUND: Angina bullosa haemorrhagica (ABH) is characterized by the recurrent appearance of blood blisters on the oral mucosa, mainly in adults' soft palate. In general, the blisters rupture spontaneously, lacking the necessity for biopsy. We report the clinical features of 23 ABH cases, emphasizing the clinical behavior and the management of these conditions. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. A total of 12,727 clinical records of oral and maxillofacial lesions from four dental services in Brazil were analyzed. Clinical data were collected from the clinical records and evaluated. RESULTS: The series comprised 12 males (52.2%) and 11 females (47.8%), with a mean age of 56.8 ± 14.6 years (ranging: 24-82 years) and a 1.1:1 male-to-female ratio. Most of the lesions affected the soft palate (n = 15, 65.2%). Clinically, the lesions presented mainly as an asymptomatic (n = 17, 73.9%) blood-filled blister that ruptured after a few minutes or hours, leaving an erosion. The masticatory trauma was the most frequent triggering event. No patient had coagulation disorders. A biopsy was performed in only four cases (17.4%). Treatment was symptomatic with a favorable outcome. CONCLUSIONS: ABH is still poorly documented in the literature, and its etiology remains uncertain. ABH mainly affects the soft palate of elderly adults and has a favorable evolution in a few days. The therapeutic approach is often focused only on the relief of symptoms. However, it can share some clinical features with more serious diseases. Therefore, clinicians must recognize these lesions to avoid misdiagnosis.

Comparative pangenomic analyses and biotechnological potential of cocoa-related Acetobacter senegalensis strains.

Acetobacter senegalensis belongs to the group of acetic acid bacteria (AAB) that present potential biotechnological applications, for production of D-gluconate, cellulose and acetic acid. AAB can overcome heat and acid stresses by using strategies involving the overexpression of heat-shock proteins and enzymes from the complex pyrroquinoline-ADH, besides alcohol dehydrogenases (ADH). Nonetheless, the isolation of A. senegalensis and other AAB from food may be challenging due to presence of viable but non-culturable (VBNC) cells and due to uncertainties about nutritional requirements. To contribute for a better understanding of the ecology of AAB, this paper reports on the pangenome analysis of five strains of A. senegalensis recently isolated from a Brazilian spontaneous cocoa fermentation. The results showed biosynthetic clusters exclusively found in some cocoa-related AAB, such as those related to terpene pathways, which are important for flavour development. Genes related to oxidative stress were conserved in all the genomes, with multiple clusters. Moreover, there were genes coding for ADH and putative ABC transporters distributed in core, shell and cloud genomes, while chaperonin-encoding genes were present only in the core and soft-core genomes. Regarding quorum sensing, a response regulator gene was in the shell genome, and the gene encoding for acyl-homoserine lactone efflux protein was in the soft-core genome. There were quorum quenching-related genes, mainly encoding for lactonases, but also for acylases. Moreover, A. senegalensis did not have determinants of virulence or antibiotic resistance, which are good traits for strains intended to be applied in food fermentation.

HIV-related non-Hodgkin lymphomas affecting the oral cavity: a clinicopathologic study of 11 cases.

BACKGROUND: HIV-related non-Hodgkin lymphomas of the oral cavity are rare lesions with aggressive clinical behaviour. The aim of this study is to describe the clinicopathological features of a series of HIV-related oral non-Hodgkin lymphomas. MATERIAL AND METHODS: Eleven cases of oral lymphomas affecting HIV-positive patients were retrieved from 2012 to 2019. Clinicopathological features regarding age, sex, tumour location, clinical presentation, laboratory findings, disease stage and follow-up were obtained. Histologic, immunohistochemical and in situ hybridization for EBV detection were done for diagnosis confirmation. Overall survival was estimated by Kaplan-Meier curve. RESULTS: Males predominated, with a mean age of 40.3 years-old. Maxilla and mandible were the mostly affected. Plasmablastic lymphoma and diffuse large B-cell lymphoma not otherwise specified (NOS) were the main histological types. Lesions presented as reddish ulcerated swellings, representing the first sign of AIDS in six cases. Stage IV were common (7 cases) and the mean HIV viral load was 10,557 copies/mL, with a mean of 266 CD4+ cells/mm3, 1,278 CD8+ cells/mm3 and a CD4+/CD8+ ratio of 0.26. Eight patients died of the disease (72.7%). Overall survival revealed that 78.2% of the patients died after 21 months of follow-up. CONCLUSIONS: HIV-related oral lymphomas present a poor prognosis usually diagnosed in advanced stages and in our series plasmablastic lymphoma was the most common subtype.

Oral Kaposi sarcoma development is associated with HIV viral load, CD4+ count and CD4+/CD8+ ratio.

BACKGROUND: Kaposi's sarcoma (KS) is an uncommon, multifocal and angioproliferative lesion, which demonstrates a poor prognosis. The aim of the present research was to explore the association of HIV viral load, CD4+ and CD8+ counts and the CD4+/CD8+ ratio on the risk of oral Kaposi's sarcoma (KS) development. MATERIAL AND METHODS: A total of 62 patients were retrieved from March 2008 to October 2020 from the files of two oral pathology centres. Clinical, laboratory and follow-up data were retrieved from their medical files. Poisson regression was used to explore the role of history of immunosuppression and its association with oral KS development. A P-value <0.05 was considered significant. RESULTS: Sixty-two patients were included in the present study (32 with oral KS and 30 with no presentation of lesions anywhere on the body). Patients with oral KS presented a mean age of 32.6 years, and male patients were more affected. The hard palate (15 cases; 46.8%) was the main anatomical site affected. The lesions were mostly presented as swellings (13 cases; 40.6%) and nodules (12 cases; 37.5%). Systemic manifestations were also observed, including candidiasis (4 cases; 12.5%), bacterial infection (3 cases; 9.3%), tuberculosis (3 cases; 9.3%), herpes simplex (3 cases; 9.3%) and pneumonia (3 cases; 9.3%). A significant correlation was observed between HIV viral load, CD4+ count and the CD4+/CD8+ ratio with oral KS development. CONCLUSIONS: HIV viral load, CD4+ count and the CD4+/CD8+ ratio are associated with oral KS development.

Metagenome-Assembled Genomes Contribute to Unraveling of the Microbiome of Cocoa Fermentation.

Metagenomic studies about cocoa fermentation have mainly reported on the analysis of short reads for determination of operational taxonomic units. However, it is also important to determine metagenome-assembled genomes (MAGs), which are genomes deriving from the assembly of metagenomics. For this research, all the cocoa metagenomes from public databases were downloaded, resulting in five data sets: one from Ghana and four from Brazil. In addition, in silico approaches were used to describe putative phenotypes and the metabolic potential of MAGs. A total of 17 high-quality MAGs were recovered from these microbiomes, as follows: (i) for fungi, Yamadazyma tenuis (n = 1); (ii) lactic acid bacteria, Limosilactobacillus fermentum (n = 5), Liquorilactobacillus cacaonum (n = 1), Liquorilactobacillus nagelli (n = 1), Leuconostoc pseudomesenteroides (n = 1), and Lactiplantibacillus plantarum subsp. plantarum (n = 1); (iii) acetic acid bacteria, Acetobacter senegalensis (n = 2) and Kozakia baliensis (n = 1); and (iv) Bacillus subtilis (n = 1), Brevundimonas sp. (n = 2), and Pseudomonas sp. (n = 1). Medium-quality MAGs were also recovered from cocoa microbiomes, including some that, to our knowledge, were not previously detected in this environment (Liquorilactobacillus vini, Komagataeibacter saccharivorans, and Komagataeibacter maltaceti) and others previously described (Fructobacillus pseudoficulneus and Acetobacter pasteurianus). Taken together, the MAGs were useful for providing an additional description of the microbiome of cocoa fermentation, revealing previously overlooked microorganisms, with prediction of key phenotypes and biochemical pathways. IMPORTANCE The production of chocolate starts with the harvesting of cocoa fruits and the spontaneous fermentation of the seeds in a microbial succession that depends on yeasts, lactic acid bacteria, and acetic acid bacteria in order to eliminate bitter and astringent compounds present in the raw material, which will be further roasted and grinded to originate the cocoa powder that will enter the food processing industry. The microbiota of cocoa fermentation is not completely known, and yet it advanced from culture-based studies to the advent of next-generation DNA sequencing, with the generation of a myriad of data that need bioinformatic approaches to be properly analyzed. Although the majority of metagenomic studies have been based on short reads (operational taxonomic units), it is also important to analyze entire genomes to determine more precisely possible ecological roles of different species. Metagenome-assembled genomes (MAGs) are very useful for this purpose; here, MAGs from cocoa fermentation microbiomes are described, and the possible implications of their phenotypic and metabolic potentials are discussed.

Total Energy Expenditure and Functional Status in Older Adults: A Doubly Labelled Water Study.

OBJECTIVES: Higher total energy expenditure in free living conditions, regardless of any activity, has been strongly associated with a lower risk of mortality in healthy older adults. Also, a good performance in physical and functional tests is a marker of good functional prognosis. However, it is not yet clear what is the association between total energy expenditure and the performance in physical and functional tests. The objective of this study was to verify the association between the total energy expenditure of older adults measured by doubly labelled water and the performance in functional tests. DESIGN: Cross-sectional study. SETTINGS AND PARTICIPANTS: Fifty-six older people were recruited from health services linked to the participating institutions. MEASUREMENTS: Socio-demographic, anthropometric and clinical characteristics were assessed through the application of a structured questionnaire. Body composition was evaluated by isotopic dilution of deuterium oxide and functional status was assessed by the gait speed test, 6-minute walk test and handgrip strength. Total energy expenditure (GET) was assessed using the doubly labelled water method and the physical activity profile was verified using an activity monitor based on accelerometery. RESULTS: The results showed that the highest total energy expenditure correlated with the best performance in the gait speed tests (r = 0.266; p = 0.047), 6-minute walk test (r = 0.424; p = 0.001) and maximum handgrip strength (r = 0.478; p = 0.000). Multivariate regression analysis in a model adjusted for sex and fat-free mass revealed an association between total energy expenditure and the 6-minute walk test (ß = 1.790; t = 2.080; p = 0.044) and the number of sedentary events ( ß = 6.389; t = 2.147; p = 0.038). CONCLUSION: The results of this study suggest that, in clinical practice, older individuals with lower gait speed, worse performance in the 6-minute walk test and lower handgrip strength, may have lower total energy expenditure, being the stimulus for its increase important for the prevention of possible problems related to low energy expenditure.

Perineurioma versus meningioma. A multi-institutional immunohistochemical and ultrastructural studY.

The differential diagnosis between perineurioma (PN) and meningioma (MEN) can be difficult by histology and immunohistochemistry (IHC) because the perineurium and arachnoid have the same embryological origin. However, there are no comparative studies determining conclusive parameters for the differential diagnosis. The aim of this study is to compare IHC of PN and MEN and their ultra-structural characteristics to elucidate which are the useful data that allow differentiate both entities. Thirty-five MEN were analyzed, and 15 PN, (11 skin and soft tissues and four oral cavity). IHC for epithelial membrane antigen (EMA), Claudin-1, GLUT-1, somatostatin-2 receptor (SSTR-2), and progesterone receptor (RP) was performed. Ultrastructural studies were performed on 8 MEN and 15 PN. Only in PN Claudin-1 was positive in 9/11 (90%) cases and GLUT-1 in 7/11 (63%) cases. In MEN, the progesterone receptor was expressed in 21/35 (60%) cases and no case expressed Claudin-1 and GLUT-1; EMA was expressed in all MEN cases and 93% of PN. SSTR-2 was expressed weakly in six cases of MEN (17%), and it was not considered useful for differential diagnosis. On ultrastructure, PN showed thin and parallel processes, some caveolae, and lacked cell junctions. The cellular processes were surrounded by a collagenous stroma in 94% of the cases. MEN were characterized by curved cytoplasmic cell processes showing desmosomes in 75% of cases. Ultrastructural findings aid in the differential diagnosis between PN and MEN, especially if molecular studies are not available.

Primary melanoma of the oral cavity: A multi-institutional retrospective analysis in Brazil.

BACKGROUND: Melanoma is an aggressive malignant tumor, rarely observed in the oral cavity. The aim of this study was to describe the clinicopathologic features of a series of oral melanomas. MATERIAL AND METHODS: A retrospective descriptive study was performed. A total of 15,482 biopsy records from two oral and maxillofacial pathology services in Brazil were analyzed. All cases of oral melanomas were reviewed, and clinical, demographic, histopathological data, treatment, and follow-up status were collected. In addition, immunohistochemistry stains (pan-cytokeratin AE1/AE3, vimentin, α-SMA, CD45, S-100 protein, HMB-45, Melan A, and Ki-67) were performed. RESULTS: The series comprised of 5 males (71.4%) and 2 females (28.6%), with a mean age of 58.0 ± 9.2 years (range: 45-69 years) and a 2.5:1 male-to-female ratio. The gingiva (n = 3, 42.8%) and hard palate (n = 2, 28.6%) were the most common affected sites, presenting clinically as ulcerated swellings with a brown to black color. Cervical lymph node metastasis was detected in three patients during the first examination. Microscopically, 6 cases (85.7%) were melanotic, and one (14.3%) was amelanotic. Most cases (n = 4, 57.1%) presented a predominance of epithelioid cells. S-100 and HMB-45 were positive in all cases (n = 7, 100.0%). In contrast, only 4 cases (57.1%) were positive for Melan-A. The proliferative index with Ki-67 was high, with labeling index ranging from 70.0% to more than 90% of positive cells. Five patients died from complications of the tumors after a mean follow-up period of 7.8 months. CONCLUSIONS: Melanoma is an aggressive malignant tumor that rarely occurs in the oral cavity. It occurs mainly in adult and elderly patients and often is diagnosed in advanced stages. The current findings were similar to previous studies and reflected the characteristics of the services from where lesions were retrieved.

Sex Hormone Depletion Augments Glucocorticoid Induction of Tau Hyperphosphorylation in Male Rat Brain.

Steroid hormones secreted by the gonads (sex steroids) and adrenal glands (glucocorticoids, GC) are known to influence brain structure and function. While levels of sex steroids wane in late adulthood, corticosteroid levels tend to rise in many individuals due to age-related impairments in their feedback on central mechanisms regulating adrenal function. These fluctuations in sex and adrenal steroid secretion may be relevant to age-related neurodegenerative disorders such as Alzheimer's disease (AD) in which hyperphosphorylation of Tau protein is a key pathological event. We here report that both, long-term GC deprivation (by adrenalectomy) and exogenous GC administration with natural or synthetic glucocorticoid receptor ligands (corticosterone and dexamethasone, respectively) induce Tau hyperphosphorylation in the hippocampus and frontocortical regions at epitopes associated with disruption of cytoskeletal and synaptic function. Interestingly, we observed that the changes in Tau induced by manipulation of the GC milieu of male rats were exacerbated by testosterone depletion (by orchiectomy). While this finding supports previous suggestions of a neuroprotective role of male sex hormones, this is the first study to address interactions between adrenal and sex steroids on Tau hyperphosphorylation and accumulation that are known to endanger neuronal function and plasticity. These results are particularly important for understanding the mechanisms that can precipitate AD because, besides being modulated by age, GC are elevated by stress, a phenomenon now established as a trigger of deficits in neural plasticity and survival, cognitive behaviour and AD-like Tau pathology.

Malignant transformation of oral leukoplakia: a multicentric retrospective study in Brazilian population.

BACKGROUND: Among the oral potentially malignant disorders, leukoplakia stands out as the most prevalent. The purpose of this study was to analyse the clinical-pathological features of oral leukoplakia in groups of patients from three major pathology centers in two different regions of Brazil, in order to determine which factors would be associated to the clinical risk of malignant transformation. MATERIAL AND METHODS: A total of 148 patients was analyzed, and data regarding gender, age, site, classification of the clinical subtype, harmful habits such as use of tobacco and alcohol, time of evolution and presence of dysplasia were collected. The association between risk factors and malignant transformation was investigated using the chi-square test and Fischer's exact test for correlation of variables. A significance level of 5% (p≤0.05) was used. RESULTS: The mean age of the patients was 60 years, and 56% were female. Most of the lesions (34,5%) were located in the lateral and ventral regions of the tongue. Of the 148 patients, ninety had clinical follow-up. Malignant transformation occurred in 13 patients (8.8%), with an average of 44 months of follow up. CONCLUSIONS: Non-smoker, nonhomogeneous clinical presentation, location at the tongue, and the presence of high degree of dysplasia were statistically relevant factors associated with a higher risk of transformation transformation.

Comparison of the whole slide imaging and conventional light microscopy in the grading of oral epithelial dysplasia: a multi-institutional study.

BACKGROUND: Whole Slide Imaging (WSI) is an alternative method to light microscopy (LM). However, few studies have compared the diagnostic agreement between WSI and LM, especially to grade oral epithelial dysplasia (OED). The purpose of this study was to evaluate the variability in grading OED by the World Health Organization grading system, using WSI and conventional LM, and to investigate whether the access to clinical information, and psychologic or physical states of the pathologists could interfere with the diagnosis. MATERIAL AND METHODS: eleven experienced pathologists from seven Brazilian universities independently evaluated twenty-five OED cases. The analyses were performed in duplicate for each method, with an interval of at least 30 days, and the time consumed in each analysis was measured. Physical and psychologic states were evaluated by blood pressure levels, heart rate and two questionnaires: State-Trait Anxiety Inventory and Perceived Stress Scale. Clinical information was provided after the second evaluation using WSI and the pathologist could change their diagnostic decision or not. RESULTS: LM showed a higher inter-examiner agreement (k=0.53) than WSI (k=0.45) and a smaller time consumed by the pathologists (mean of 65.53 seconds compared to 91.02 seconds in WSI). In the first analysis using conventional microscopy, there was a positive correlation between kappa values and anxiety (r=0.47, p=0.02), and stress (r=0.64, p<0.01), and an inverse correlation with heart rate (r=-0.48, p=0.02). In the digital analysis, there was also a positive correlation between kappa values and anxiety (r=0.75, p<0.001). After clinical information was given, there was a slight change in 11.3% of the cases, and a great discrepancy in 1.1% of the cases, mainly increasing the OED grade. CONCLUSIONS: both microscopy systems had similar results, although LM had slightly higher kappa values, and WSI was more time consuming.

Oral pigmented lesions: a retrospective analysis from Brazil.

BACKGROUND: Pigmented lesions are uncommon in the oral mucosa, and studies investigating the incidence and types of these lesions are desired to improve the diagnostic knowledge of clinicians. The aim of this study was to analyze the distribution of oral pigmented lesions in a Brazilian population. MATERIAL AND METHODS: A retrospective descriptive cross-sectional study was performed. Oral pigmented lesions were retrieved from the files of two oral and maxillofacial pathology services from Brazil over a 45-year period (1974-2019). The clinical data and the diagnoses of each case were retrieved and included in a Microsoft Excel® database. RESULTS: From 77.074 lesions diagnosed in this period, 761 (0.99%) represented pigmented lesions of the oral mucosa, including 351 (46.1%) melanocytic and 410 (53.9%) non-melanocytic lesions, with a higher incidence in females (73.2%) between the fourth and seventh decades of life. Amalgam tattoo (53.6%) represented the most common lesion, followed by melanotic macule (18.3%) and racial pigmentation (10.8%). Other pigmented lesions included nevus (9.9%), post-inflammatory pigmentation (3%), melanoma (2.1%), melanoacanthoma (1.4%), smoker's melanosis (0.4%), drug-induced pigmentation (0.3%), and melanotic neuroectodermal tumor of infancy (0.1%). The buccal mucosa was the most commonly affected site (25.2%), followed by the alveolar ridge (14.5%), and gingiva (11.8%). CONCLUSIONS: The current findings were similar to previous studies with minor differences due methodology and characteristics of the services from where lesions were retrieved. The knowledge of these data may contribute to a better understanding of oral pigmented lesions and assist clinicians to better recognize and manage them.