Radiographic Orofacial Findings of Systemic Diseases.

This article discusses the orofacial clinicoradiographic features of systemic diseases that manifest in the orofacial region. The systemic diseases discussed are grouped into the following: autoimmune diseases, endocrine diseases, bone diseases, hematologic diseases, syndromes, and malignancies. The radiographic manifestation ranges from radiolucent bony destruction, increased bone density, calcification, thinning of cortical plate, loss of trabeculation, missing teeth, and supernumerary teeth. It is imperative for clinicians to be cognizant of these findings, as they may be the first manifestation of these systemic diseases.

Cemento-Osseous Dysplasia of the Jaw: Demographic and Clinical Analysis of 191 New Cases.

Cemento-osseous dysplasia (COD) is a form of benign fibro-osseous lesion of the jaw. We sought to evaluate the demographic and clinical presentations of COD by collecting and analyzing the demographic, clinical, radiographic, and pathologic data of COD diagnosed in our institution from 2017 to 2022. Over this six-year period, the records of 191 patients with COD were reviewed. Most patients were African American and female. Eighty-five patients were diagnosed with florid COD (FLCOD), 63 with periapical COD (PCOD), and 43 with focal COD (FCOD). Twenty-eight (14.7%) patients presented symptoms. The most common symptom was pain. All the symptomatic cases of COD that were histopathologically diagnosed were osteomyelitis in the setting of COD. Symptomatic patients were older (mean of 61.3 years) than the asymptomatic patients (mean of 51.2 years). Due to the radiographic appearance of a radiolucency or a mixture of radiolucency and radiopacity, forty-five asymptomatic patients were biopsied. Most of the asymptomatic patients biopsied were patients with FCOD (n = 19, 54.3%), followed by PCOD (n = 16, 25.8%), and FLCOD (n = 10, 15.2%). FLCOD is the most common form of COD to present with symptoms. Due to the significant overlap in clinical and radiographic presentation with other entities, FCOD and PCOD remain a diagnostic challenge to dentists. In conclusion, we analyzed the demographic and clinical features of 191 new cases of COD, which reaffirms that cemento-osseous dysplasia is a condition that primarily affects middle-aged females of African descent and occurs more frequently in the mandible.

Structural conservation of Lassa virus glycoproteins and recognition by neutralizing antibodies.

Lassa fever is an acute hemorrhagic fever caused by the zoonotic Lassa virus (LASV). The LASV glycoprotein complex (GPC) mediates viral entry and is the sole target for neutralizing antibodies. Immunogen design is complicated by the metastable nature of recombinant GPCs and the antigenic differences among phylogenetically distinct LASV lineages. Despite the sequence diversity of the GPC, structures of most lineages are lacking. We present the development and characterization of prefusion-stabilized, trimeric GPCs of LASV lineages II, V, and VII, revealing structural conservation despite sequence diversity. High-resolution structures and biophysical characterization of the GPC in complex with GP1-A-specific antibodies suggest their neutralization mechanisms. Finally, we present the isolation and characterization of a trimer-preferring neutralizing antibody belonging to the GPC-B competition group with an epitope that spans adjacent protomers and includes the fusion peptide. Our work provides molecular detail information on LASV antigenic diversity and will guide efforts to design pan-LASV vaccines.

Herpesvirus-Related Lesions of the Oral Mucosa.

The human herpesvirus (HHV) family is a group of enveloped DNA viruses containing 8 members known to produce oral mucosal lesions. Following initial exposure, which may result in symptomatic primary infection, the viruses establish latency within specific cells/tissues. After reactivation, herpesviruses can cause localized symptomatic or asymptomatic recurrent (secondary) infections or diseases. HHV may have a significant role in the cause of oral mucosal infectious diseases in immunocompromised patients. This article discusses the role of those herpesviruses that can induce oral mucosal lesions, with focus on the clinical features and treatment/management.

MAML2-Rearranged Primary Central Mucoepidermoid Carcinoma of the Mandible as an Incidental Finding: A Case Report and Review of the Literature of Molecularly Confirmed Cases.

This report presents an extremely rare case of MAML2-rearranged primary central mucoepidermoid carcinoma (MEC) of the mandible that was discovered as an incidental finding. Our review of the literature identified 36 cases of MAML2-rearranged intraosseous lesions of the jaw (30 central MECs, 5 odontogenic cysts with mucous prosoplasia, and 1 glandular odontogenic cyst). Given the therapeutic indications for a diagnosis of MEC (a malignant neoplasm), MAML2 rearrangement should be confirmed in suspected cases of central MEC.

Clinicopathologic Study of Sialadenoma Papilliferum of the Minor Salivary Glands: A Series of 8 New Cases With BRAF V600E Mutation-specific Immunohistochemical Analysis.

Introduction. Sialadenoma papilliferum (SP) is a rare benign neoplasm that usually arises in the minor salivary glands. Recently, it was demonstrated that SP shares similar molecular genetic alterations (BRAF V600E or HRAS mutations) with its morphologic analog, syringocystadenoma papilliferum. Methods. We sought to perform clinicopathologic and immunophenotypic (BRAF V600E and SOX10) analyses on 8 new cases of SP. Results. The cases were from 4 males and 4 females, with ages ranging from 28 to 81 years (average: 64 years). The common locations were the hard palate (n = 3) and buccal mucosa (n = 3). Histopathologically, 7 cases were classic and 1 case was oncocytic. BRAF V600E immunohistochemistry (IHC) was positive in all classic SP, involving both the exophytic and endophytic components, but negative in the oncocytic SP. SOX10 was positive in the endophytic ductal cells of the evaluated classic SP but was negative in the oncocytic SP. Conclusions. We report 8 new cases of this rare salivary gland neoplasm, using BRAF V600E and SOX10 IHC to further support the following points: (1) the functional role of BRAF V600E mutation, RAS/mitogen-activated protein kinase signaling pathway in the pathogenesis of classic SP of salivary glands by IHC; (2) the analogous relationship between SP, syringocystadenoma papilliferum, and papillary seromucinous adenocarcinoma with sinonasal papilloma-like surface component (PSASP-like surface); (3) endophytic ductal component in classic SP arises from the intercalated ducts and not the excretory ducts; and (4) oncocytic SP is distinct from classic SP.

Microsecretory Adenocarcinoma of Salivary Glands: An Expanded Series of 24 Cases.

Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases. All cases of MSA were obtained from the authors' files. Immunohistochemistry for S100, SOX10, p63, p40, SMA, calponin, and mammaglobin was performed. Molecular analysis was performed by targeted RNA sequencing, SS18 break apart fluorescence in situ hybridization, and/or reverse transcriptase polymerase chain reaction for MEF2C-SS18 fusion. Clinical follow-up was obtained from medical records. A total of 24 MSA cases were collected, from 13 women and 11 men, ranging from 17 to 83 years (mean 49.5 years). The vast majority (23 of 24) arose in the oral cavity, with the palate (n = 14) and buccal mucosa (n = 6) as the most frequent subsites. Tumors showed consistent histologic features including: (1) microcystic tubules, (2) flattened intercalated duct-like cells, (3) monotonous oval hyperchromatic nuclei, (4) abundant basophilic luminal secretions, (5) fibromyxoid stroma, and (6) circumscribed borders with subtle infiltration. The tumors were very consistently positive for S100 (24 of 24), p63 (24 of 24), and SOX10 (14 of 14) and negative for p40 (0 of 21), calponin (0 of 12) and mammaglobin (0 of 16), while SMA (4 of 20) was variable. MEF2C-SS18 fusion was demonstrated in 21 of 24 cases; in the remaining 3 cases with insufficient RNA, SS18 break apart FISH was positive. Treatment information was available in 17 cases, all of which were managed with surgery only. In 14 cases with follow-up (1-216 months, mean 30), no cases recurred or metastasized. MSA is a distinct salivary gland neoplasm with remarkably consistent clinical, histologic, immunophenotypic, and genetic features that generally behaves in an indolent manner following surgery alone. These observations solidify MSA as a unique, low-grade salivary gland carcinoma that warrants inclusion in the next version of the WHO classification of head and neck tumors.

RNAi-mediated gene knockdown and in vivo diuresis assay in adult female Aedes aegypti mosquitoes.

This video protocol demonstrates an effective technique to knockdown a particular gene in an insect and conduct a novel bioassay to measure excretion rate. This method can be used to obtain a better understanding of the process of diuresis in insects and is especially useful in the study of diuresis in blood-feeding arthropods that are able to take up huge amounts of liquid in a single blood meal. This RNAi-mediated gene knockdown combined with an in vivo diuresis assay was developed by the Hansen lab to study the effects of RNAi-mediated knockdown of aquaporin genes on Aedes aegypti mosquito diuresis. The protocol is setup in two parts: the first demonstration illustrates how to construct a simple mosquito injection device and how to prepare and inject dsRNA into the thorax of mosquitoes for RNAi-mediated gene knockdown. The second demonstration illustrates how to determine excretion rates in mosquitoes using an in vivo bioassay.

SLC7 amino acid transporters of the yellow fever mosquito Aedes aegypti and their role in fat body TOR signaling and reproduction.

BACKGROUND: An important function of the fat body in adult female mosquitoes is the conversion of blood meal derived amino acids (AA) into massive amounts of yolk protein precursors. A highly efficient transport mechanism for AAs across the plasma membrane of the fat body trophocytes is essential in order to deliver building blocks for the rapid synthesis of large amounts of these proteins. This mechanism consists in part of AA transporter proteins from the solute carrier family. These transporters have dual function; they function as transporters and participate in the nutrient signal transduction pathway that is activated in the fat body after a blood meal. In this study we focused on the solute carrier 7 family (SLC7), a family of AA transporters present in all metazoans that includes members with strong substrate specificity for cationic AAs. METHODOLOGY/PRINCIPAL FINDINGS: We identified 11 putative SLC7 transporters in the genome sequence of Aedes aegypti. Phylogenetic analysis puts five of these in the cationic AA transporter subfamily (CAT) and six in the heterodimeric AA transporter (HAT) subfamily. All 11 A. aegypti SLC7 genes are expressed in adult females. Expression profiles are dynamic after a blood meal. We knocked down six fat body-expressed SLC7 transporters using RNAi and found that these 'knockdowns' reduced AA-induced TOR signaling. We also determined the effect these knockdowns had on the number of eggs deposited following a blood meal. CONCLUSIONS/SIGNIFICANCE: Our analysis stresses the importance of SLC7 transporters in TOR signaling pathway and mosquito reproduction.

AaCAT1 of the yellow fever mosquito, Aedes aegypti: a novel histidine-specific amino acid transporter from the SLC7 family.

Insect yolk protein precursor gene expression is regulated by nutritional and endocrine signals. A surge of amino acids in the hemolymph of blood-fed female mosquitoes activates a nutrient signaling system in the fat bodies, which subsequently derepresses yolk protein precursor genes and makes them responsive to activation by steroid hormones. Orphan transporters of the SLC7 family were identified as essential upstream components of the nutrient signaling system in the fat body of fruit flies and the yellow fever mosquito, Aedes aegypti. However, the transport function of these proteins was unknown. We report expression and functional characterization of AaCAT1, cloned from the fat body of A. aegypti. Expression of AaCAT1 transcript and protein undergoes dynamic changes during postembryonic development of the mosquito. Transcript expression was especially high in the third and fourth larval stages; however, the AaCAT1 protein was detected only in pupa and adult stages. Functional expression and analysis of AaCAT1 in Xenopus oocytes revealed that it acts as a sodium-independent cationic amino acid transporter, with unique selectivity to L-histidine at neutral pH (K(0.5)(L-His) = 0.34 ± 0.07 mM, pH 7.2). Acidification to pH 6.2 dramatically increases AaCAT1-specific His(+)-induced current. RNAi-mediated silencing of AaCAT1 reduces egg yield of subsequent ovipositions. Our data show that AaCAT1 has notable differences in its transport mechanism when compared with related mammalian cationic amino acid transporters. It may execute histidine-specific transport and signaling in mosquito tissues.