Early life stress exacerbates bone resorption and inhibits anxiety-like behaviour induced by apical periodontitis in rats.

AIM: To evaluate the influence of the early life stress (ELS) on the severity of the apical periodontitis (AP) in Wistar rats. METHODOLOGY: Forty male Wistar rats were divided into four groups (n = 10): Control rats; AP-rats with AP; ELS-rats subject to ELS; AP + ELS-rats exposed to ELS and subject to AP. ELS was induced by maternal separation (MS) for a period of 3 h for 21 consecutive days. AP was induced via pulp exposure of the first and second right maxillary molars to the oral environment for 40 days. Three days before euthanasia, all rats underwent behavioural analysis to measure anxiety levels by elevated zero maze. Then, the rats were euthanized and the maxillas were removed to assess the occurrence and severity of AP. The periapical region was evaluated for the intensity of the inflammatory infiltrate and the extent of bone loss. The Mann-Whitney test was performed for nonparametric data, and the Tukey's or Student's t-test was performed for parametric data (p < .05). RESULTS: The intensity of the inflammatory infiltrate was significantly larger in the AP + ELS group when compared with AP group (p < .05). The AP + ELS group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 103.5 ± 29.88, compared with 72.3 ± 22.28 in the AP group (p < .05). Rats with AP displayed higher anxiety-like behaviour in relation to the control group (p < .05). However, exposure to ELS abolished the AP-induced increased anxiety-like 'behaviour' throughout, since that rats from AP + ELS group attended more the open arms than non-stressed rats with AP (p < .05). CONCLUSION: Early life stress is predictive of the severity of AP exacerbating the inflammatory process and increasing periapical bone resorption.

Pleomorphic sarcoma of maxillary sinus: Clinical report of a patient initially diagnosed with denture-induced fibrous hyperplasia.

Undifferentiated pleomorphic sarcoma is a high-grade soft-tissue malignant tumor that is rare in the head and neck region. A 74-year-old woman displayed a large nodular lesion in the maxillary alveolar mucosa, which was initially identified as denture-related fibrous hyperplasia. Although her prosthodontist has adjusted the maxillary complete denture to relieve pressure on the lesion, it increased in size over time. Computed tomography images of the maxillary sinus showed an extensive destructive lesion. A biopsy was performed, and microscopic examination revealed a poorly differentiated malignancy with numerous spindle cells. Immunohistochemistry reactions were negative for CD45, CD30, CD68, CD34, cytokeratin, S100, desmin, and smooth muscle actin. These findings led to the diagnosis of an undifferentiated pleomorphic sarcoma of the maxillary sinus.

Assessment of the knowledge of canalis sinuosus amongst dentists and dental students: An online-based cross-sectional study.

INTRODUCTION: Canalis sinuosus (CS) is a neurovascular canal that corresponds to a small branch of the infraorbital canal. This study aimed at assessing the knowledge and detection performance of CS amongst dentists and dental students. MATERIALS AND METHODS: Four-hundred and five dentists and dental students answered a questionnaire with three parts: 1. Socio-demographical; 2. Clinical cases with cone- beam computed tomography (CBCT) sections showing CS and 3. Previous knowledge about CS. The chi-squared test and Spearman's correlation test were used to compare results as appropriate. p-values below .05 were considered statistically significant. RESULTS: Most participants did not identify CS in any CBCT. There was an association between the number of correct answers and dental specialties. Most individuals had not learned about CS previously. There was an association between past knowledge of CS and gender, highest academic degree, working environment, dental specialty and number of correct answers but not with age or experience in Dentistry. CONCLUSION: This study suggests that most dentists are not aware about CS and do not know how to diagnose it. Previous knowledge about CS positively influenced its identification in CBCT.

Diagnosis and Treatment of Oral Venous Malformation in a Child.

Venous malformations (VMs) are congenital disorders that constitute about 40% of all vascular anomalies. These lesions do not regress spontaneously and may increase in size during childhood. The case of a 10-year-old girl with an extensive oral VM is reported. Intraoral examination revealed the presence of purplish nodules in the alveolar mucosa and gingiva from anterior maxilla. Doppler ultrasound showed a well-defined hypoechoic image and increased vascularization with low blood flow for the alveolar mucosa lesion. The patient was submitted to intralesional injections of the ethanolamine oleate/mepivacaine sclerosing solution. After four sessions, there was a significant reduction of the lesions. However, the patient abandoned the treatment and the oral VM grew progressively. After 1 year, sclerotherapy was resumed and performed weekly. After 10 session of sclerotherapy, the oral VM totally regressed. The childhood is a critical period for oral VM growth. Doppler ultrasound and sclerotherapy can be effective for the management of extensive lesions in children.

Benign symmetric lipomatosis in the tongue: an uncommon case.

Symmetric lipomatosis of the tongue (SLT) is rare and characterized by diffuse growth and unencapsulated lipomas. An 87-year-old man was referred for evaluation of tongue lesions. Intraoral findings showed soft yellowish nodules with a smooth shiny surface diffusely on the lateral border of the tongue, bilaterally. Our clinical diagnosis was multiple tongue lipomas and an incisional biopsy was done. Histopathological examination revealed unencapsulated lobules of mature adipocytes with slight variation in the size and shape, confirming the diagnosis of lipoma. The final diagnosis was SLT. On follow-up at 6 months, the tongue findings were unchanged and no new lesions were observed.

Childhood trauma is predictive for clinical staging, alcohol consumption, and emotional symptoms in patients with head and neck cancer.

BACKGROUND: Traumatic events in childhood have been associated with the occurrence of anxiety and depression in adulthood. This relation has been investigated in patients with breast cancer; however, it has been little explored in patients with other types of cancer. The objective of this study was to evaluate the occurrence of childhood trauma in patients with head and neck cancer and its association with clinicopathological variables and anxiety and depression levels. METHODS: The study included 110 patients with head and neck squamous cell carcinoma (HNSCC) before they started cancer treatment. Clinicopathological and biobehavioral data were collected from patients' medical records. Anxiety and depression levels were assessed with the Beck Anxiety Inventory and the Beck Depression Inventory, respectively. The Childhood Trauma Questionnaire was used to evaluate the occurrence of traumatic events in childhood. RESULTS: One hundred five patients (95.5%) experienced at least 1 type of childhood trauma. Emotional neglect was the most reported childhood trauma (43.8%), and multiple regression revealed that it was an independent variable for advanced clinical staging (ß = 2.15, P = .048) and higher alcohol consumption (ß = 2.32, P = .031). Patients with HNSCC who experienced more traumatic events in childhood had an almost 12 times greater chance of increased depression levels during the pretreatment period (ß = 11.89; P = .0002). The occurrence of physical child neglect was a predictive factor for increased anxiety levels (ß = 4.17, P = 0.029). CONCLUSIONS: Traumatic events in childhood are predictive for advanced clinical staging, alcohol consumption, and emotional symptoms in patients with HNSCC, and they should be considered in clinical and psychological intervention strategies during cancer treatment. Cancer 2018;000:000-000. © 2018 American Cancer Society.

Extra-Gingival Pyogenic Granuloma Displacing Teeth.

Pyogenic granuloma is a common cause of growth of soft tissue in the oral cavity, especially in the gingiva. It is mainly associated with local and chronic irritants besides hormonal changes during pregnancy. Here, the authors present an unusual patient of an extra-gingival pyogenic granuloma with large dimensions and displacing teeth arising in a male patient. This is an interesting patient to be reported due to its exacerbated and atypical clinical features.

LARGE2-dependent glycosylation confers laminin-binding ability on proteoglycans.

Both LARGE1 (formerly LARGE) and its paralog LARGE2 are bifunctional glycosyltransferases with xylosy- and glucuronyltransferase activities, and are capable of synthesizing polymers composed of a repeating disaccharide [-3Xylα1,3GlcAß1-]. Post-translational modification of the O-mannosyl glycan of α-dystroglycan (α-DG) with the polysaccharide is essential for it to act as a receptor for ligands in the extracellular matrix (ECM), and both LARGE paralogs contribute to the modification in vivo. LARGE1 and LARGE2 have different tissue distribution profiles and enzymatic properties; however, the functional difference of the homologs remains to be determined, and α-DG is the only known substrate for the modification by LARGE1 or LARGE2. Here we show that LARGE2 can modify proteoglycans (PGs) with the laminin-binding glycan. We found that overexpression of LARGE2, but not LARGE1, mediates the functional modification on the surface of DG-/-, Pomt1-/- and Fktn-/- embryonic stem cells. We identified a heparan sulfate-PG glypican-4 as a substrate for the LARGE2-dependent modification by affinity purification and subsequent mass spectrometric analysis. Furthermore, we showed that LARGE2 could modify several additional PGs with the laminin-binding glycan, most likely within the glycosaminoglycan (GAG)-protein linkage region. Our results indicate that LARGE2 can modify PGs with the GAG-like polysaccharide composed of xylose and glucuronic acid to confer laminin binding. Thus, LARGE2 may play a differential role in stabilizing the basement membrane and modifying its functions by augmenting the interactions between laminin globular domain-containing ECM proteins and PGs.

Lip Cancer: A Clinicopathological Study and Treatment Outcomes in a 25-Year Experience.

PURPOSE: There are few clinical studies focusing on treatment outcomes of lip cancer. This study investigated the clinicopathologic variables of a large sample of patients with lip squamous cell carcinoma (LSCC) treated in a reference head and neck cancer center for the past 25 years and analyzed the influence of these variables on treatment outcomes. MATERIALS AND METHODS: This retrospective cohort study reviewed the clinical records of patients with LSCC. Epidemiologic data were age, gender, ethnicity, type of occupation, tobacco smoking, alcohol consumption, comorbid conditions, and family cancer history. Clinicopathologic features included the lip location of the tumor, TNM classification, clinical staging, histopathologic grade, surgical margin analysis, and treatment modality. Local recurrence, second primary tumor, and survival were the outcome variables. Statistical analysis was performed by χ(2) test, Fisher exact test, and binary logistic regression analysis. Survival analysis was assessed through the Kaplan-Meier curve. Level of statistical significance was set at a P value less than .05 for all tests. RESULTS: In total, 144 patients with LSCC were studied. There were 117 men (81.25%) and 27 women (18.75%) with a mean age of 60.21 years. One hundred thirty-four patients (93.05%) were considered of white ethnicity, and in 57 cases (39.58%), the patients reported an occupation that was related to long-term solar exposure. Most cancers had initial clinical staging of 1 or 2 (84.02%). Microscopically, lesions were predominantly well (43.05%) and moderately (40.96%) differentiated tumors. Clinical staging was related to a specific higher survival rate (P = .0049). One hundred twelve cases (77.78%) underwent surgical treatment and only 6 patients (4.80%) had local recurrence, which was directly associated with compromised surgical margins (P = .0320). CONCLUSION: A high success rate in LSCC treatment was observed in this study. Compromised surgical margin was associated with tumor recurrence and is a critical event in lip cancer treatment.

Pemphigus Vulgaris: How to Perform an Oral Biopsy Properly?

Oral biopsy of vesiculobullous diseases such as pemphigus vulgaris often raises questions due to some particularities involving this procedure. The adequate selection of the area to be biopsied defines if the final diagnosis will be reached, being the Achiles heel of the proper management of the patient. Here, the authors report a case of a woman who sought for treatment of generalized oral blisters and ulcers that caused severe pain. She had undergone a previous biopsy by other professionals that was inconclusive. The authors' team diagnosed the patient with pemphigus vulgaris and treated her properly. The authors provide a brief discussion about the adequate oral site to be chosen when dealing with vesiculobullous diseases once it still remains a source of doubts for the dental surgeons.

Oral squamous cell carcinoma misdiagnosed as a denture-related traumatic ulcer: A clinical report.

A 65-year-old woman presented with an ulcerated lesion in the alveolar ridge mucosa, which appeared after new dentures had been inserted. Despite many treatment attempts, the lesion did not recede, even with the interruption of denture wearing. A biopsy was performed, and histopathologic examination revealed an ulcerated, invasive, poorly differentiated oral squamous cell carcinoma. The time from the patient's first contact with the prosthodontist because of the lesion until the appropriate diagnosis was established was approximately 6 months. This clinical report documents a significant delay in the oral squamous cell carcinoma diagnosis and treatment because of a clinical misdiagnosis of a traumatic ulcer resulting from complete dentures. Prosthodontists should be aware of the importance of early diagnosis of oral cancer among elderly prosthesis wearers.

Lollipop-induced oral lichenoid reaction in a child.

BACKGROUND: Oral lichenoid reactions (OLRs) have been rarely reported in pediatric patients. CASE REPORT: This article reports an unusual case of a 15-year-old girl who had white plaques in tongue and buccal mucosa oral which initially were diagnosed as oral lichen planus (OLP). At first, the patient and her family denied systemic or local medication use. Biopsy was performed, and histopathological aspects were suggestive of OLP. Despite the attempt of treatment with topical corticoid, the lesions did not recede. Patient's behavior and medical history were again investigated and revealed that she had been using almost daily in her school an artificially colored and flavored lollipop. One week after removing lollipop use behavior, the oral lesions showed complete resolution and OLR diagnosis was defined. CONCLUSION: The present case denotes that OLR should be considered in the differential diagnosis of oral white plates in children and artificially colored sweets can be its causal agent.

Loss of LARGE2 disrupts functional glycosylation of α-dystroglycan in prostate cancer.

Dystroglycan (DG) is a cell surface receptor for extracellular matrix proteins and is involved in cell polarity, matrix organization, and mechanical stability of tissues. Previous studies documented loss of DG protein expression and glycosylation in a variety of cancer types, but the underlying mechanisms and the functional consequences with respect to cancer progression remain unclear. Here, we show that the level of expression of the ßDG subunit as well as the glycosylation status of the αDG subunit inversely correlate with the Gleason scores of prostate cancers; furthermore, we show that the functional glycosylation of αDG is substantially reduced in prostate cancer metastases. Additionally, we demonstrate that LARGE2 (GYLTL1B), a gene not previously implicated in cancer, regulates functional αDG glycosylation in prostate cancer cell lines; knockdown of LARGE2 resulted in hypoglycosylation of αDG and loss of its ability to bind laminin-111 while overexpression restored ligand binding and diminished growth and migration of an aggressive prostate cancer cell line. Finally, our analysis of LARGE2 expression in human cancer specimens reveals that LARGE2 is significantly down-regulated in the context of prostate cancer, and that its reduction correlates with disease progression. Our results describe a novel molecular mechanism to account for the commonly observed hypoglycosylation of αDG in prostate cancer.

A dystroglycan mutation associated with limb-girdle muscular dystrophy.

Dystroglycan, which serves as a major extracellular matrix receptor in muscle and the central nervous system, requires extensive O-glycosylation to function. We identified a dystroglycan missense mutation (Thr192→Met) in a woman with limb-girdle muscular dystrophy and cognitive impairment. A mouse model harboring this mutation recapitulates the immunohistochemical and neuromuscular abnormalities observed in the patient. In vitro and in vivo studies showed that the mutation impairs the receptor function of dystroglycan in skeletal muscle and brain by inhibiting the post-translational modification, mediated by the glycosyltransferase LARGE, of the phosphorylated O-mannosyl glycans on α-dystroglycan that is required for high-affinity binding to laminin.

IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma.

BACKGROUND: Cancer pain severely limits function and significantly reduces quality of life. Subtypes of sensory neurons involved in cancer pain and proliferation are not clear. METHODS: We produced a cancer model by inoculating human oral squamous cell carcinoma (SCC) cells into the hind paw of athymic mice. We quantified mechanical and thermal nociception using the paw withdrawal assays. Neurotoxins isolectin B4-saporin (IB4-SAP), or capsaicin was injected intrathecally to selectively ablate IB4(+) neurons or TRPV1(+) neurons, respectively. JNJ-17203212, a TRPV1 antagonist, was also injected intrathecally. TRPV1 protein expression in the spinal cord was quantified with western blot. Paw volume was measured by a plethysmometer and was used as an index for tumor size. Ki-67 immunostaining in mouse paw sections was performed to evaluate cancer proliferation in situ. RESULTS: We showed that mice with SCC exhibited both mechanical and thermal hypersensitivity. Selective ablation of IB4(+) neurons by IB4-SAP decreased mechanical allodynia in mice with SCC. Selective ablation of TRPV1(+) neurons by intrathecal capsaicin injection, or TRPV1 antagonism by JNJ-17203212 in the IB4-SAP treated mice completely reversed SCC-induced thermal hyperalgesia, without affecting mechanical allodynia. Furthermore, TRPV1 protein expression was increased in the spinal cord of SCC mice compared to normal mice. Neither removal of IB4(+) or TRPV1(+) neurons affected SCC proliferation. CONCLUSIONS: We show in a mouse model that IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Bilateral intra-lymph node Warthin's tumor as a potential diagnostic pitfall mimicking metastatic carcinoma.

Warthin's tumor (WT) is a benign and frequent salivary gland tumor primarily affecting the parotid gland. In some cases, this tumor can involve the extra parotid region and affect cervical lymph nodes. Fine-needle aspiration can be the first step in the diagnostic approach to lymphadenopathy; however, specimens from intra-nodal WT can present a potential pitfall, leading to a misdiagnosis of metastasis. Here, we report an unusual case of a patient with bilateral WT in parotid lymph nodes misdiagnosed as metastases. In addition, we highlight the cytopathological aspects of WT to alert cytopathologists about this challenging diagnosis.

Expression of ß1- and ß2-adrenergic receptors in oral squamous cell carcinoma and their association with psychological and clinical factors.

BACKGROUND: Psychological stressors have been related to tumor progression through the activation of beta-adrenergic receptors (ß-AR) in several types of cancer. PURPOSE: This study aimed to investigate the expressions of ß1- and ß2-AR and their association with psychological and clinicopathological variables in patients with oral squamous cell carcinoma. METHODS: Tumor samples from 99 patients diagnosed with OSCC were subjected to immunohistochemical reaction to detect the expression of ß1-AR and ß2-AR. Anxiety and depression symptoms were assessed using the Beck Anxiety Inventory and Beck Depression Inventory (BDI), respectively. The Brunel Mood Scale was used for measuring affective mood states. RESULTS: Univariate analyzes revealed that higher expression of ß1-AR was associated with increased alcohol consumption (p = 0.032), higher education (p = 0.042), worse sleep quality (p = 0.044) and increased levels of pain related to the primary tumor (p < 0.001). Higher expression of ß2-AR was related with regional metastasis (p = 0.014), increased levels of pain related to the primary tumor (p = 0.044), anxiety (p < 0.001) and depressive (p = 0.010) symptoms and higher mood scores of angry (p = 0.010) and fatigue (p = 0.010). Multivariate analysis identified that patients with advanced clinical stage had lower ß1-AR expression (OR=0.145, 95% CI=0.025-0.828, p = 0.003). Higher anxiety symptoms and higher mood fatigue are independent factors for increased ß2-AR expression (OR=4256, 95% CI=1439-12606, p = 0.009; OR=3816, 95% CI=1258-11,573, p = 0.018, respectively). CONCLUSION: This study reveal that anxiety, fatigue symptoms, and clinical staging are associated with tumor expression of beta-adrenergic receptors in patients with oral cancer.