RESUMO Objetivo: Avaliar a associação entre os eventos periparto e o desenvolvimento do transtorno do espectro autista (TEA) em crianças/adolescentes. Métodos: Trata-se de um estudo de caso-controle desenvolvido no norte de Minas Gerais, Brasil. Os critérios de inclusão do grupo caso foram indivíduos com diagnóstico de TEA por laudo médico, confirmado pela Associação Norte Mineira de Apoio ao Autista ou por clínicas especializadas, e as mães que responderam positivamente a: “Seu filho foi diagnosticado com TEA?”. Assim, o grupo caso incluiu 253 mães de crianças/adolescentes com 2–15 anos diagnosticadas com autismo. O critério de inclusão no grupo controle abrangeu 852 indivíduos pertencentes à mesma faixa etária e matriculados nas mesmas escolas que o grupo caso. Um questionário semiestruturado foi aplicado às mães e o modelo de regressão logística múltipla foi adotado para a análise de dados. Para estimar a magnitude das associações, utilizou-se Odds Ratio (OR) bruta e ajustada. Resultados: O TEA foi associado à presença de mecônio no líquido amniótico (ORa 1,67; intervalo de confiança [IC95%] 1,06–2,65) e ao parto cesáreo (ORa 1,65; IC95% 1,17–2,32). A cesárea de emergência aumentou a chance de desenvolvimento do autismo (ORa 2,38; IC95% 1,61–3,51). Crianças/adolescentes com autismo apresentaram maior chance de exposição a dois ou mais eventos desfavoráveis de parto (ORa 1,59; IC95% 1,01–2,51). Conclusões: A presença de mecônio no líquido amniótico, cesárea de emergência e mais de um evento de parto desfavorável são fatores que devem ser considerados nos estudos sobre a etiologia do transtorno autístico.

Abstract Objective: To assess the association between peripartum events and autism spectrum disorder (ASD) development in children and adolescents. Methods: The current research is a case–control study in northern Minas Gerais state, Brazil. The inclusion criteria in the case group included individuals whose medical records reported an autistic disorder diagnosis, individuals had this diagnosis further confirmed by Northern Minas Autistic Support Association and specialized clinics, and their mothers had to answer positively to the question: “Was your child diagnosed with autism spectrum disorder?” in the data collection instrument. Thus, the case group included 253 mothers of children/adolescents of 2–15 years old diagnosed with autism. The inclusion criteria in the control group included 852 individuals belonging to the same age group and enrolled in the same schools as the case group. A semi-structured questionnaire was applied for mothers of children/adolescents, and the multiple logistic regression model was adopted for data analysis. Gross and adjusted Odds Ratios (ORa) were used to estimate the magnitude of the associations. Results: Autistic disorder was associated with the presence of meconium in amniotic fluid (AF) (ORa 1.67; 95% confidence interval [95%CI] 1.06–2.65) and cesarean delivery type (ORa 1.65; 95%CI 1.17–2.32). Emergency cesarean section increased autistic disorder development likelihood (ORa 2.38; 95%CI 1.61–3.51). Children and adolescents with ASD were more likely to have been exposed to two or more unfavorable peripartum events and obstetric complications than control groups (ORa 1.59; 95%CI 1.01–2.51). Conclusions: Meconium stained amniotic fluid, delivery by cesarean, and two or more unfavorable peripartum events are variables that should be considered in studies about ASD etiology.

ABSTRACT: Pazopanib, an antiangiogenic agent, has shown promising results in controlling tumor growth and metastasis in patients with renal cell carcinoma. The use of pazopanib in the management of malignancies has increased over recent years, with more patients at risk of developing medication-related osteonecrosis of the jaw (MRONJ). This paper presents the first case report of MRONJ associated with pazopanib monotherapy. A 59-year-old man was referred to the dental clinic with complaints of dysphagia and dysgeusia. The patient was prescribed pazopanib (400 mg) daily following surgical treatment and chemotherapy for metastatic renal cell carcinoma. He had undergone extraction of the maxillary left second premolar nine weeks previously. Intraoral examination revealed exposed necrotic bone, which was treated effectively with leukocyte and platelet-rich fibrin (LPRF). The patient was followed up for 150 days after dental treatment with no signs of relapse.

RESUMEN: Pazopanib, un agente antiangiogénico, ha mostrado resultados prometedores en el control del crecimiento tumoral y las metástasis en pacientes con carcinoma de células renales. El uso de pazopanib en el tratamiento de las neoplasias malignas ha aumentado en los últimos años, con más pacientes en riesgo de desarrollar osteonecrosis de la mandíbula relacionada con la medicación (MRONJ). Este artículo presenta el primer reporte de caso de MRONJ asociado con la monoterapia con pazopanib. Un hombre de 59 años fue remitido a la clínica dental con quejas de disfagia y disgeusia. Al paciente se le prescribió pazopanib (400 mg) al día tras tratamiento quirúrgico y quimioterapia por carcinoma metastásico de células renales. Había sido sometido a extracción del segundo premolar superior izquierdo nueve semanas antes. El examen intraoral reveló hueso necrótico expuesto, que fue tratado eficazmente con leucocitos y fibrina rica en plaquetas (LPRF). El paciente fue seguido durante 150 días después del tratamiento dental sin signos de recidiva.

Abstract Objective Neutrophils are key effector cells of the innate immune system. They recognize antigens through membrane receptors, which are expressed during their maturation and activation. Neutrophils express FcγRII (CD32), FcγRIII (CD16), and FcγRI (CD64) after being activated by different factors such as cytokines and bacterial products. These receptors are involved with phagocytosis of IgG-opsonized microbes and enhance defense mechanisms. Based on that, our study seeks to compare the expression of FcγRII, FcγRIII, FcγRI, and CD11b on neutrophils from elderly and young subjects and their expression after in vitro activation with cytokines and LPS. Methodology Neutrophils were isolated from human peripheral blood and from mice bone marrow by density gradient. After isolation, FCγRs expression was immediately analyzed by flow cytometry or after in vitro stimulation. Results In freshly isolated cells, the percentage of FcγRIIIb+ and CD11b+ neutrophils were higher in samples from young individuals; FcγRIIIa expression was more prominent on aged neutrophils; FcγRIA expression was similar in all samples analyzed. Exposure to CXCL8 and LPS resulted in a higher percentage of FcγRIa+ neutrophils on elderly individuals’ samples but lower when compared with neutrophils from young donors. We observed that LPS caused an increase in FcγRIIa expression on aging human neutrophils. In contrast, FcγRIIIb expression in response to CXCL8 and LPS stimulation was not altered in the four groups. CD11b expression was lower in neutrophils from elderly individuals even in response to LPS and CXCL8. In mice, we observed differences only regarding CD11b expression, which was increased on aged neutrophils. LPS exposure caused an increase in all FcγRs. Conclusions Our results suggest that, in humans, the overall pattern of FcγR expression and integrin CD11b are altered during aging and immunosenescence might contribute to age-related infection.

RESUMO Objetivo: Investigar a associação entre o transtorno do espectro autista (TEA) e as coocorrências de transtornos psiquiátricos entre familiares de crianças/adolescentes do norte de Minas Gerais, Brasil. Métodos: Realizou-se um estudo de caso-controle constituído por 248 indivíduos com o TEA (casos) e 886 neurotípicos (controles). Foi aplicado um questionário semiestruturado e adotou-se o modelo de regressão logística múltipla na análise dos dados. Para estimar a magnitude das associações, utilizou-se a razão de chances (odds ratio – OR) bruta e ajustada. Resultados: Observou-se associação positiva e significativa entre o TEA e a presença de familiares com: qualquer transtorno psiquiátrico (OR: 3,68; intervalo de confiança de 95% [IC95%]: 2,68-5,05), com TEA (OR: 3,37; IC95%: 2,09-5,43), com transtorno do déficit de atenção e hiperatividade (TDAH) (OR: 2,19; IC95%: 1,41-3,39) e com epilepsia (OR: 1,91; IC95%: 1,20-2,98). Conclusão: Este estudo sugere que crianças/adolescentes com TEA têm maior chance de ter história familiar de desordens psiquiátricas, especialmente TEA, TDAH e epilepsia. Esses achados podem ter importantes implicações tanto para a Psiquiatria Clínica quanto para a Saúde Pública, uma vez que podem ser usados para formar um perfil clínico de pessoas com transtorno psiquiátrico que correm risco de ter familiar com TEA.

ABSTRACT Objective: To investigate the association between ASD and cooccurrences of psychiatric disorders among relatives of children/adolescents from northern Minas Gerais, Brazil. Methods: A case-control study was performed, consisting of 248 individuals with ASD (cases) and 886 neurotypical controls. A semi-structured questionnaire and the multiple logistic regression model were adopted in the data analysis. To estimate the magnitude of associations, the crude and adjusted odds ratio (OR) was used. Results: There was a positive and significant association between ASD and the presence of relatives with: any psychiatric disorder (OR: 3.68; 95% confidence interval [95%CI]: 2.68-5.05), with ASD (OR: 3,37; 95%CI: 2.09-5.43), with ADHD (OR: 2.19; 95%CI: 1.41-3.39) and epilepsy (OR: 1.91; 95%CI: 1.20-2.98). Conclusion: This study suggests that children/adolescents with ASD have a higher chance of family history of psychiatric disorders, especially ASD, ADHD and epilepsy. These findings may have important implications for both Clinical Psychiatry and Public Health, as they can be used to form a clinical profile of people with psychiatric disorders who are at risk of having a family member with ASD.

Abstract Research on cancer stem cells (CSCs) has greatly increased in the field of medicine and pathology; however, some conceptual misunderstandings are still present among the public as well as within the general scientific community that is not yet familiar with the subject. The very first problem is the misinterpretation of CSCs as a synonym of their normal counterparts, the well-known stem cells (SCs). Particularly in Dentistry, another common mistake is the misinterpretation of oral CSCs as normal tooth-derived SCs. The present review aims to clarify important concepts related to normal SCs and CSCs, as well as discuss the relevance of CSCs to the development, metastasis and therapy resistance of oral squamous cell carcinoma.

Abstract Elderly denture wearers are commonly affected by Candida-associated denture stomatitis (DS), an inflammatory process of the oral mucosa strongly associated with Candida spp and other microorganisms, as well as local and systemic factors. The impaired immune response against pathogens is among the inherent host factors that have been also associated with the pathogenesis of DS. Mononuclear phagocytes respond to the pathogens through phagocytosis followed by the production of several substances inside the phagosomes, among them are the reactive nitrogen species (RNS). A failure in these mechanisms may contribute to the DS development. Objective The aim of this study was to investigate the influence of aging on the internalization and the production of nitric oxide (NO) by peritoneal adherent cells (PAC), in response to Candida albicans (C. albicans). Material and methods PAC obtained from young and aged mice were challenged with dead or viable C. albicans by using predetermined proportions (cells:yeast) for 30 and 120 minutes. Phagocytosis was analyzed by acridine orange dye, and NO production by the Griess reaction. Results C. albicans phagocytosis by PAC from aged mice was similar to that of young mice, although the cells from older mice cells present more internalized fungi compared with matched control. In addition, a tendency towards impaired NO production by peritoneal mononuclear phagocytes from aged mice was observed. Conclusions PAC from aged mice may capture and store many fungi, which in turn may mean that these cells are effectively unable to eliminate fungi, probably due to impaired NO production. Therefore, considering the important role of C. albicans overgrowth in the pathogenesis of DS and the aspects observed in this study, aging may favor the onset and severity of local candidosis such as DS and its systemic forms.

Abstract Lipomas are very common benign slow-growing soft tissue neoplasms composed of mature adipose tissue mostly diagnosed in the fifth decade of life. These tumors rarely present in the oral cavity, representing less than approximately 5% of all benign mouth tumors. They are usually less than 2cm in size and etiology remains unclear. We report a young male patient presenting with a giant lipoma in the buccal mucosa. Histopathology revealed a large area of mature fat cells consistent with conventional lipoma and an area of the mucosal lining of the lesion suggestive of morsicatio buccarum. In the present article, we emphasize the clinicopathological features and differential diagnosis of the disease.

Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05). Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis. Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

Asymptomatic mouth floor enlargements may be observed in edentulous patients. These masses, which protrude from the mouth floor, may complicate the fitting of dentures and require surgery. Whether this "entity" may be considered an anatomical variation of the mouth floor or represent specific alterations in the sublingual gland is not known. Objective: The aim of this work is to investigate the morphological and morphometric aspects of the sublingual glands of edentulous patients with mouth floor enlargements and compare the glands of these patients with the sublingual glands of human cadavers. Material and Methods: Microscopic evaluation was performed on human sublingual glands from edentulous patients with mouth floor enlargements (n=20) and edentulous cadavers (n=20). The patients and cadavers were of similar ages. The data were compared using Mann-Whitney U, Fisher's exact and Student's t tests (p<0.05). Results: Acinar atrophy, duct-like structures, mononuclear infiltrates, replacement of parenchyma with fibrous/adipose tissue, mucous extravasation and oncocytosis were similar between the groups (p>0.05). Only the variables "autolysis" and "congested blood vessels" presented statistical difference between groups (p=0.014; p=0.043). The morphometric study revealed that the volume densities of acini, ducts, stroma and adipose tissue were similar between the groups (p>0.05). CONCLUSION: The microscopic characteristics of the sublingual glands in mouth floor enlargements in edentulous patients correspond to characteristics associated with the normal aging process. The glands are not pathological and represent an age-related alteration that occurs with or without the presence of the mouth floor enlargements.

The calcifying epithelial odontogenic tumour is a rare benign odontogenic neoplasm that accounts for approximately 1% of all odontogenic tumours. They are mainly located in the premolar/molar mandibular region, and are associated with an unerupted molar tooth. We present a literature review of the clinical, radiographic, pathological findings and treatment options of the calcifying epithelial odontogenic tumour, as well as describing the case of an calcifying epithelial odontogenic tumour associated with an impacted right mandibular in a 32-year-old male patient, who was treated conservatively, without no sign of recurrence of the lesion after five years.

El tumor epitelial odontogénico calcificante corresponde a menos de 1% de todos los tumores odontogénicos de origen ectodérmica, afectando principalmente la región posterior de la mandíbula, relacionada muchas veces a un diente molar retenido. En este artículo son realizadas las consideraciones en relación a las características clínicas, radiográficas, histopatológicas y sobre las modalidades de tratamiento del tumor epitelial odontogénico calcificante por medio de una revisión de literatura, siendo relatado la asociación de un tumor de este tipo a un canino inferior retenido, en un paciente de género masculino, de 32 años de edad, tratado de forma conservadora y en el cual no se observó recurrencia de la lesión después de 5 años de acompañamiento.

Pleomorphic adenoma (PA), the most common salivary gland tumor, accounts for 54 to 65% of all salivary gland neoplasias and 80% of the benign salivary gland tumors. It most frequently affects the parotid gland, followed by the submandibular and the minor salivary glands. Microscopically, mucous, sebaceous, oncocytic and squamous metaplasia, sometimes with the formation of keratin pearls, may be present, but the latter rarely results in the formation of extensive keratin-flled cysts lined by squamous epithelium. Extensive squamous metaplasia can be mistaken for malignancy, including mucoepidermoid carcinoma and squamous cell carcinoma. Here, we present an unusual case of PA with extensive squamous metaplasia and keratin cyst formations in a minor salivary gland, and discuss its microscopic features, including the immunohistochemical characteristics, and differential diagnosis of this uncommon presentation.

A falha primária de erupção é caracterizada pelo não irrompimento de um dente sem que haja impedimento mecânico ou que o dente esteja em posição anormal ou devido à causas sistêmicas. É um fenômeno raro e não foi associado com alterações do folículo dentário. Este relato descreve um caso de falha primária de erupção de um primeiro molar inferior direito permanente, localizado na base da mandíbula, que apresenta achados clínicos, radiográficos e microscópicos compatíveis com cisto folicular. O folículo pericoronário deste molar apresentou aspectos microscópicos de inflamação. Assim como os tecidos pericoronários dos dentes não irrompidos, a longo prazo, os folículos pericoronários dos dentes com falha primária de irrompimento têm o potencial para desenvolver cistos odontogênicos. Esta lesão provavelmente surgiu em associação com uma bolsa periodontal na mesial do segundo molar adjacente, caracterizando um cisto folicular inflamatório atípico. Este caso apresenta características etiológicas, radiográficas e microscópicas comuns nos cistos foliculares inflamatórios associados a dentes decíduos infectados, com exceção das infecções que alcançam o folículo. São discutidas ainda as controvérsias relativas à terminologia deste cisto.

Primary failure of eruption represents a cessation of tooth eruption before emergence not due to a physical barrier or abnormal position and has no systemic cause. This failure of tooth eruption is rare phenomenon and it has not been associated with alterations of dental follicle. This case report describes a permanent right first molar with primary failure of eruption at the inferior border of the mandible presenting microscopic, clinical and radiographic findings compatible with follicular cystic lesion. The follicular tissues of this molar showed microscopic aspects of inflammation. Thus, pericoronal tissues surrounding long-term unerupted teeth with primary failure of eruption has potential to develop into odontogenic cysts. The lesion presented herein probably arose in association with a periodontal pocket mesial to the adjacent second molar, representing an atypical inflammatory follicular cyst. This case shares etiological, radiological and microscopic features with the usual form of the inflammatory follicular cyst associated with infected primary teeth, except for the infection pathways reaching the tooth follicle. The controversies regarding the terminology for this cyst are discussed.

A paracoccidioidomicose é uma doença granulomatosa crônica que induz resposta inflamatória e imune específica. A participação do óxido nítrico (NO), produto da enzima óxido nítrico sintase induzível (iNOS), como uma importante molécula fungicida contra o fungo Paracoccidioides brasiliensis tem sido demonstrada. Com o objetivo de melhor caracterizar as lesões orais da paracoccidioidomicose (OP), propusemos estudo imunohistoquímico das células iNOS+ e das células CD45RO+, CD3+, CD8+, CD20+, CD68+ e mastócitos. As amostras foram distribuídas em grupos de acordo com o número de fungos viáveis por mm². Nossos resultados demonstraram leve imunomarcação para iNOS nas células gigantes multinucleadas (MNGC) e na maioria das células mononucleares (MN), e a proporção de células MN/MNGC iNOS+ na OP foi comparável a do grupo Controle (tecido bucal clinicamente saudável). Adicionalmente, nossa análise revelou similaridade no número de células CD4+ entre o Controle e o grupo de OP com elevado número de fungos. Estes achados sugerem que a baixa expressão de iNOS e a diminuição de células CD4+ na OP podem representar possíveis mecanismos que permitiram a multiplicação local do fungo e a manutenção das lesões bucais ativas.

Paracoccidioidomycosis is a chronic granulomatous disease that induces a specific inflammatory and immune response. The participation of nitric oxide (NO), a product of the inducible nitric oxide synthase enzyme (iNOS), as an important fungicidal molecule against Paracoccidioides brasiliensis has been demonstrated. In order to further characterize the Oral Paracoccidioidomycosis (OP), we undertook an immunohistochemical study of iNOS+, CD45RO+, CD3+, CD8+, CD20+, CD68+ cells and mast cells. The samples were distributed in groups according to the number of viable fungi per mm². Our results showed weak immunolabeling for iNOS in the multinucleated giant cells (MNGC) and in most of the mononuclear (MN) cells, and the proportion of iNOS+ MN/MNGC cells in the OP were comparable to Control (clinically healthy oral tissues). Additionally, our analysis revealed a similarity in the number of CD4+ cells between the Control and the OP groups with higher numbers of fungi. These findings suggest that a low expression of iNOS and a decrease in the CD4+ T cells in OP may represent possible mechanisms that permit the local fungal multiplication and maintenance of active oral lesions.