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Background: The initiation of odontogenic tumorigenesis often involves the activation of the MAP-kinase pathway, with a pivotal role played by the BRAF V600E mutation. This study aimed to investigate the frequency of BRAF V600E immunoexpresion in ameloblastomas diagnosed in four Latin American centers and correlate this finding with the histological types and subtypes of the analyzed cases., Material and Methods: A total of 86 samples of ameloblastomas were examined for immunohistochemistry using anti-BRAF V600E antibody. The histopathological features of each case were analyzed., Results: Positivity for anti-BRAF V600E antibody was detected in 65/86 cases (75.6%). BRAF V600E was positive in 38/56 cases (67.9%) of conventional ameloblastomas and in 27/30 cases (90.0%) of unicystic ameloblastomas. A statistically significant difference in BRAF V600E positivity was observed when comparing unicystic ameloblastomas to conventional ameloblastomas (p=0.03). No statistically significant difference in BRAF V600E positivity was observed when comparing histological variants, both for conventional ameloblastomas and unicystic ameloblastomas., Conclusions: This study highlights a high frequency of BRAF V600E immunoreactivity in ameloblastomas among Latin American cases. The prevalence of the BRAF V600E immunoexpresion may suggest the feasibility of utilizing BRAF-targeted therapy for ameloblastomas with this mutation.

Paracoccidioidomycosis (PCM) is a chronic mycosis caused by the saprobic and dimorphic species Paracoccidioides brasiliensis and P. lutzii. This disease is prevalent in Latin American countries. PCM appears as a relevant concern and challenge for the mycologists, since until now there is no a methodology suitable for an efficient and safe diagnosis and species identification. Thus, the present study aimed to validate a methodology for PCM´s diagnosis, using quantitative Polymerase Chain Reaction (qPCR) through target amplification of the gene encoding the recombinant protein Pb27, a common protein to the both species Paracoccidioides brasiliensis and P. lutzii. The experiments were performed in vitro to determine the specificity, efficiency and detection limit of qPCR assay, using specific primers and probe, which sequences were subject to a patent deposited in Brazilian CTIT, under the registration number: BR1020160078830. According to the results the technique showed sensitivity of 94% and specificity of 100%, demonstrating that it will be possible to develop a new fast and safe diagnostic PCM and can be standardized in order to present a low cost, accessible to the patient served by the public health system in Brazil and Latin America., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Paracoccidioidomycosis is a systemic mycosis endemic to Latin America, with Paracoccidioides brasiliensis and P. lutzii being the causal agents of this disorder. Several issues have been raised in the 100 years since its discovery and in this article we discuss features of this fascinating fungal pathogen, including its biology, eco-epidemiology and aspects of its pathogenicity. We also consider some of its virulence determinants, the most recent advances in the study of its metabolic pathways and the molecular and genetic research tools developed for this research. We also review the animal models used to study host-fungal interactions and how the host defence mechanisms against this pathogen work., (Copyright © 2015 John Wiley & Sons, Ltd.)

The epidemiological characteristics of paracoccidioidomycosis were reviewed and updated. The new endemic areas in Brazil were discussed in the section regarding the geographic distribution of the mycosis. Subclinical infection with Paracoccidioides brasiliensis was discussed on the basis of skin test surveys with antigens of the fungus, seroepidemiological studies, and disease cases outside Latin America. Large case series permitted a comparison of the prevalence of the mycosis in different regions, its estimated incidence and risk factors for the development of the disease. Aspects modulating the expression of the clinical forms of paracoccidioidomycosis are also presented. This review also deals with diseases associated with the mycosis, opportunistic paracoccidioidomycosis, lethality, mortality and infection and disease in animals.

Paracoccidioidomycosis is a subacute or chronic systemic mycosis caused by Paracoccidioides brasiliensis, a soil saprophyte and thermally dimorphic fungus. The disease occurs mainly in rural workers in Latin America and is the most frequent endemic systemic mycosis in many countries of South America, where almost 10 million people are believed to be infected. Paracoccidioidomycosis should be regarded as a disease of travelers outside the endemic area. The primary pulmonary infection is subclinical in most cases, and individuals may remain infected throughout life without ever developing clinical signs. A small proportion of patients present with clinical disease. The lungs are frequently involved, and the pulmonary clinical manifestations must be differentiated from many other infectious and noninfectious conditions. Diagnosis should be based on epidemiological, clinical, and microbiological data. Effective treatment regimens are available to control the fungal infection, but most patients develop fibrotic sequelae that may severely hamper respiratory and adrenal function and the patient's well-being., (© Thieme Medical Publishers.)

Although endemic mycoses are a frequent health problem in Latin American countries, clinical and epidemiological data remain scarce and fragmentary. These mycoses have a significant impact on public health, and early diagnosis and appropriate treatment remain important. The target population for endemic disease in Latin America is mostly represented by low-income rural workers with limited access to a public or private health system. Unfortunately, diagnostic tools are not widely available in medical centers in Latin America; consequently, by the time patients are diagnosed with fungal infection, many are already severely ill. Among immunocompromised patients, endemic mycoses usually behave as opportunistic infections causing disseminated rather than localized disease. This paper reviews the epidemiology of the most clinically significant endemic mycoses in Latin America: paracoccidioidomycosis, histoplasmosis, and coccidioidomycosis. The burdens of disease, typically affected populations, and clinical outcomes also are discussed.

Paracoccidioidomycosis, one of the most important endemic and systemic mycoses in Latin America, presents several clinical pictures. Epidemiological studies indicate a striking rarity of disease (but not infection) in females, but only during the reproductive years. This suggested a hormonal interaction between female hormones and the etiologic dimorphic fungus Paracoccidioides brasiliensis. Many fungi have been shown to use hormonal (pheromonal) fungal molecules for intercellular communication, and there are increasing numbers of examples of interactions between mammalian hormones and fungi, including the specific binding of mammalian hormones by fungal proteins, and suggestions of mammalian hormonal modulation of fungal behavior. This suggests an evolutionary conservation of hormonal receptor systems. We recount studies showing the specific hormonal binding of mammalian estrogen to proteins in P. brasiliensis and an action of estrogen to specifically block the transition from the saprophytic form to the invasive form of the fungus in vitro. This block has been demonstrated to occur in vivo in animal studies. These unique observations are consistent with an estrogen-fungus receptor-mediated effect on pathogenesis. The fungal genes responsive to estrogen action are under study.

Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin America. Recently, the existence of three genetically isolated groups in P. brasiliensis was demonstrated, enabling comparative studies of molecular evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for putative virulence factors were analyzed to determine whether they were under positive selection. Our maximum likelihood-based approach yielded evidence for selection in 12 genes that are involved in different cellular processes. An in-depth analysis of four of these genes showed them to be either antigenic or involved in pathogenesis. Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection. The other three genes (fks, cdc42 and p27) show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection. Our results are consistent with the more general observations that selective constraints are variable across the genome, and that even in the genes under positive selection, only a few sites are altered. We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

Paracoccidioides brasiliensis is a dimorphic and thermo-regulated fungus which is the causative agent of paracoccidioidomycosis, an endemic disease widespread in Latin America that affects 10 million individuals. Pathogenicity is assumed to be a consequence of the dimorphic transition from mycelium to yeast cells during human infection. This review shows the results of the P. brasiliensis transcriptome project which generated 6,022 assembled groups from mycelium and yeast phases. Computer analysis using the tools of bioinformatics revealed several aspects from the transcriptome of this pathogen such as: general and differential metabolism in mycelium and yeast cells; cell cycle, DNA replication, repair and recombination; RNA biogenesis apparatus; translation and protein fate machineries; cell wall; hydrolytic enzymes; proteases; GPI-anchored proteins; molecular chaperones; insights into drug resistance and transporters; oxidative stress response and virulence. The present analysis has provided a more comprehensive view of some specific features considered relevant for the understanding of basic and applied knowledge of P. brasiliensis.

Paracoccidioides brasiliensis is an amenable model to study the molecular and biochemical events that lead to morphological transition in fungi, because temperature seems to be the only factor regulating this process. It is the causative agent of paracoccidioidomycosis, a systemic mycosis that affects humans and that is geographically confined to Latin America, where it constitutes one of the most prevalent deep mycoses. With the help of molecular tools, events leading to the morphological transition have been traced to genes that control cell wall glucan and chitin syntheses, and other metabolic processes such as production of heat shock proteins and ornithine decarboxylase activity. Molecular diagnosis and epidemiology of paracoccidioidomycosis are also the focus of intensive research, with several primers being proposed as specific probes for clinical and field uses. Although P. brasiliensis is refractory to cytogenetic analysis, electrophoretic methods have allowed an approximation of its genomic organization and ploidy. Finally, the recognition of P. brasiliensis as an anamorph in the phylum Ascomycota, order Onygenales, family Onygenaceae, has been accomplished by means of molecular tools. This phylogenetic placement has revised the taxonomic position of this fungus, which was traditionally included within now-abandoned higher anamorph taxa, the phylum Deuteromycota and the class Hyphomycetes.

Randomly amplified polymorphic DNA (RAPD) analysis of 33 Paracoccidioides brasiliensis strains from Argentina, Brazil, Colombia, Peru, and Venezuela produced reproducible amplification products which were sufficiently polymorphic to allow differentiation of the strains. Types generated with five primers (OPG 03, OPG 05, OPG 14, OPG 16, and OPG 18) resulted in a high discriminatory index (0.956). The discriminatory index was slightly reduced (0.940) when only two primers (OPG 3 and OPG 14) were used. A dendrogram based on these results showed a high degree of similarity among the strains, and genetic differences were expressed in clusters related to geographical regions but not to pathological features of the disease. With a few exceptions, strains were sorted into five groups by geographical origin as follows: group I, Venezuelan strains; group II, Brazilian strains; group III, Peruvian strains; group IV, Colombian strains; and group V, Argentinian strains. The group containing the most disparate strains was group V (discriminatory index, 0.633); the discriminatory index for the other four groups was 0.824. The use of primer OPG 18 by itself was sufficient to discriminate species specificity, and the use of primer OPG 14 by itself was sufficient to discriminate among the geographical locations of the strains in the sample. This method may be helpful for epidemiological studies of P. brasiliensis.

Fungal infections remain a frequent health problem in Latin American countries. Although these diseases exhibit an extraordinary heterogeneity, they have certain features in common. Most patients belong to low socioeconomic groups and live in rural areas. This article presents a general view of the most prevalent subcutaneous mycoses, with emphasis on epidemiology, clinical manifestations, laboratory diagnosis, and treatment options in the developing countries of Latin America.