The Frequency of Risk Factors for Cleft Lip and Palate in Mexico: A Systematic Review.

BACKGROUND: Cleft lip and palate is an anomaly that affects both women and men. It is considered to be among the most frequent congenital abnormalities and is related to modifications in chromosomal DNA and multiple genetic alterations. This anomaly can also be associated with various environmental factors, such as tobacco and alcohol consumption, medication use, and exposure to different environmental and industrial toxic substances. The objective of this study was to document the frequency of risk factors related to cleft lip and palate through a systematic review of Mexican studies. METHODS: In this systematic review, a bibliographic search was conducted following PRISMA guidelines in the databases Scielo, ScienceDirect, PubMed, and EBSCO. Keywords related to cleft lip and palate, epidemiology, and risk factors were used. In all, 3 independent reviewers (J.A.S.L., S.L.V., and N.M.F.) selected and evaluated a total of 17 articles included in this analysis, achieving a coefficient of κ = 0.84. RESULTS: The analysis revealed that the highest frequency of conducted studies was in the State of Mexico. The most common risk factors identified were environmental, pharmacological, consumption habits, and gynecological factors. CONCLUSIONS: Identifying the main risk factors for cleft lip and palate in the Mexican population will enable the implementation of preventive measures aimed at reducing exposure to these factors. Additionally, early intervention can improve the quality of life for individuals affected by this condition.

Association between fluoride intake from drinking water and severity of dental fluorosis in Northern and Western Mexico: systematic review and meta-analysis.

BACKGROUND: Dental fluorosis (DF) is caused by excessive exposure to fluoride during odontogenesis and leads to various changes in the development of tooth enamel. Some regions in Mexico are considered endemic fluorosis zones due to the high fluoride content in drinking water. The objective of this study was to perform a systematic review and meta-analysis to identify the association between the concentration of fluoride in drinking water and the severity of dental fluorosis in northern and western Mexico. METHODS: This protocol was registered in the PROSPERO database (ID: CRD42023401519). The search for information was carried out in the PubMed/Medline, Scopus, SpringerLink, and Google Scholar databases between January 2015 and October 2023. The overall relative risk was calculated using the inverse of variance approach with the random effects method. The RoB 2.0 tool was used to construct risk plots. RESULTS: Eleven articles were analyzed qualitatively, and most of the included studies presented at least one level of DF severity; six articles were analyzed quantitatively, dividing them into two regions. In North region it was observed a higher prevalence of severe TF cases, corresponding to ≥ TF 5 category (4.78) [3.55, 6.42]. In the West region, most of the included studies presented a higher prevalence of less severe cases, corresponding to ≤ TF 4, in comparison with the North region (0.01) [0.00, 0.52], interpreted as a protective effect. CONCLUSION: The concentrations of fluorides in drinking water are reportedly high in these regions and are directly related to the severity of dental fluorosis experienced by the inhabitants. In the Northern region exists a major concentration of fluoride in drinking water compared with the Western region as well as a prevalence of higher severity cases of dental fluorosis.

DNA oxidative damage in oral cancer: 8-hydroxy-2´-deoxyguanosine immunoexpression assessment

Background: The development and establishment of oral squamous cell carcinoma are confined to carcinogenesis, which involves oxidative stress via oxygen-free radical production as a hydroxyl radical (HO•), considered the most important cause of oxidative damage to basic biomolecules since it targets DNA strands. 8-Hydroxy-2´- deoxyguanosine (8-OHdG) is considered a free radical with a promutagenic capacity due to its ability to pair with adenosine instead of cytosine during replication. Material and Methods: We collected 30 paraffin-embedded tissue samples of OSCC from patients treated between 2013 and 2018. We recorded risk habits, disease stage, disease free survival and death with at least 3 years of followup. 8-Hydroxyguanosine was evaluated by immunohistochemistry and subsequently classified as weak-moderate or strong positive expression. Additionally, we noted whether it was expressed in the cytoplasm and/or nucleus. Results: Most of the cases expressed 8-OHdG with a strong intensity (80%). All neoplastic cells were preferentially stained in only the cytoplasm (70.0%), but nuclear positivity was found in 30%, independent of the intensity. Based on the location in the cytoplasm and/or nucleus, tumors >4 cm showed a high frequency (95.5%) of 8-OHdG expression in only the cytoplasm, with a significant difference (p value ≤ 0.001). Additionally, overall survival was affected when immunoexpression was present in the cytoplasm and nucleus because all deaths were in this group were statistically significant (p value = 0.001). Conclusions: All tumors showed DNA oxidative damage, and 8-OHdG was preferentially expressed in the cytoplasm. This finding was associated with tumor size and, when present in the nucleus, might also be related to death. (AU)

Connexin 43 expression in tooth germ and benign odontogenic tumors.

OBJECTIVE: The aim of this study was to investigate and compare the immunohistochemical expression of connexin 43 (Cx43) in tooth germs (TGs), ameloblastic fibromas (AFs), ameloblastic fibro-odontomas (AFOs), and conventional ameloblastomas (AMs). STUDY DESIGN: Nine TGs, 12 AFs, 12 AFOs, and 27 AMs were evaluated for Cx43 expression by immunohistochemistry. RESULTS: Most of the TGs expressed Cx43 in the mesenchyme (77.6%) and in the late stages of odontogenesis. Cx43 was more highly expressed (P < .05) in the mesenchymal layer of all groups than in the epithelial layer except for the AFOs. When comparing the expression of Cx43 in the different layers of the analyzed groups, statistically significant differences were observed between AFO vs AM (*P = .0158) in the epithelial layer and between AF vs AFO (P** = .0046) in the mesenchymal layer. CONCLUSIONS: The results obtained in this study showed that Cx43 is a protein with important expression in the mesenchymal layer of the embryonic and odontogenic tissues studied. It could be speculated that Cx43 participates in mineralization events based on the relationship of the expression of this protein between the epithelial and mesenchymal layers of odontogenic tissues.

Starting from scratch: Step-by-step development of diagnostic tests for SARS-CoV-2 detection by RT-LAMP.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Public health strategies to reduce viral transmission are based on widespread diagnostic testing to detect and isolate contagious patients. Several reverse transcription (RT)-PCR tests, along with other SARS-CoV-2 diagnostic assays, are available to attempt to cover the global demand. Loop-mediated isothermal amplification (LAMP) based methods have been established as rapid, accurate, point of care diagnostic tests for viral infections; hence, they represent an excellent alternative for SARS-CoV-2 detection. The aim of this study was to develop and describe molecular detection systems for SARS-CoV-2 based on RT-LAMP. Recombinant DNA polymerase from Bacillus stearothermophilus and thermostable engineered reverse transcriptase from Moloney Murine Leukemia Virus were expressed using a prokaryotic system and purified by fast protein liquid chromatography. These enzymes were used to set up fluorometric real time and colorimetric end-point RT-LAMP assays. Several reaction conditions were optimized such as reaction temperature, Tris-HCl concentration, and pH of the diagnostic tests. The key enzymes for RT-LAMP were purified and their enzymatic activity was determined. Standardized reaction conditions for both RT-LAMP assays were 65°C and a Tris-HCl-free buffer at pH 8.8. Colorimetric end-point RT-LAMP assay was successfully used for viral detection from clinical saliva samples with 100% sensitivity and 100% specificity compared to the results obtained by RT-qPCR based diagnostic protocols with Ct values until 30. The developed RT-LAMP diagnostic tests based on purified recombinant enzymes allowed a sensitive and specific detection of the nucleocapsid gene of SARS-CoV-2.

A Systematic Review and Meta-Analysis of the Relationship Between the Severity of Dental Fluorosis and Fluoride Biomarkers in Endemic Areas.

The intake of high concentrations of fluoride, mainly through drinking water, diet and fluoridated dentifrices, produces fluorosis, which in its early stages is manifested as dental fluorosis (DF). To recognize exposure to fluoride in endemic areas and to evaluate the risk of developing health impairment, the WHO has established several biomarkers that are used to determine systemic fluorine (F-) exposure. Thus, the aim of this study was to conduct a systematic review and meta-analysis of the relationship between the severity of DF and fluoride biomarkers in endemic areas. The protocol of this study was previously registered as CRD42021244974. A digital search was carried out in PubMed/Medline, SpringerLink, Scopus, Cochrane and Google Scholar by employing the keywords "urine", "nails", "hair", "plasma", "saliva" and "dental fluorosis" for the original studies with content associated with F- for the biomarkers and DF. The mean difference was established as the effect measure for the meta-analysis. Seven studies fulfilled the eligibility criteria, among which five assessed urine and two employed nails as fluoride biomarkers. A positive significant difference was found between the biomarkers and the severity of DF (0.27, p < 0.001) and individually for each biomarker (urine: 0.14, p = 0.001; nails: 0.88, p < 0.05). The F- concentration in urine and nails is correlated with the severity of DF, with the most evident differences between healthy individuals and those with mild severity. Both biomarkers are adequate to assess this relationship in endemic areas of fluoride and DF.

Periodontal Disease in Obese Patients; Interleukin-6 and C-Reactive Protein Study: A Systematic Review.

Periodontal disease (PD) and obesity are characterized by a dysregulated inflammatory state. Both conditions trigger inflammatory and immune responses with an increase in proinflammatory cytokines such as Interleukin 6 (IL-6) and the release of inflammatory mediators such as C-reactive protein (CRP). Individuals with a high body mass index (BMI) present a chronic inflammatory state. The aim of the present study was to perform a systematic review of inflammatory markers (IL-6 and CRP) in obese patients with PD and their possible relationship by analyzing the levels of these markers. A digital literature search was performed in three databases-PubMed, SciElo and Medigraphic-through an advanced search for original articles, employing IL-6 and CRP in obese patients with PD, within a publication period from 2010 to 2021. PRISMA guidelines, the JADAD scale and a qualitative analysis of scientific evidence were performed using the Cochrane collaboration method and the RoB 2 assessment tool. Ten articles were included in this analysis with the variables recorded and associated with subjects with obesity and PD. Of the ten articles included, three analyzed IL-6 and CRP, four analyzed IL-6 and three analyzed CRP. In conclusion, and based on the available evidence, the aforementioned markers of inflammation demonstrate that there is a relationship between PD and obesity.

Ep-CAM (MOC-31) expression in tooth germ and ameloblastoma

Background: Ep-CAM, a transmembrane glycoprotein expressed in most epithelium in normal conditions, hasdiverse roles in these tissues, including in cell adhesion, proliferation, differentiation, cell cycle regu-lation, migration and intracellular signaling. It is also over-expressed in most malignant neoplasia, partic-ipating in theinitiation, progression, and metastatic dissemination of the tumor. The expression and roles of this protein in oralneoplasia, particularly in odontogenic tumors, remain unestablished. The objective of this study consisted in analyzing the expression of this protein in ameloblastoma and tooth germ.Material and Methods: Ep-CAM (MOC-31) expression was evaluated by immunohistochemistry in tooth germs(TG) (n = 16) ameloblastomas (AM) (n = 60) and 2 ameloblastic carcinomas. Sections were visualized in theirtotality with an optical microscope, and positivity observed in cell membrane and cytoplasm was graded according to the following semi-quantitative scale: Neg, "essentially unstained", for negative sections or staining <5% ofcells; + for staining of 5-50% of cells; ++ for staining >50% of cells.Results: Most tooth germs expressed MOC-31 (81.3%), strong staining was observed both in the inner epitheliumof the enamel organ and in the adjacent stellate reticulum. 16.7% of the AM cases showed MOC-31 expression,the immunoexpression expression was diffuse at the cytoplasmic and membrane level. The only two cases ofameloblastic carcinoma included were strong positive to MOC-31. No correlation was observed between proteinexpression and gender, age, clinical variants, or histological subtypes.Conclusions: Overexpression was found in TG and ameloblastic carcinoma compared to AM; further studies withdifferent experimental strategies are suggested to clarify the biological significance of this finding. (AU)

Self-Reported Periodontal Disease and Its Association with SARS-CoV-2 Infection.

Introduction: Knowledge of the oral manifestations associated with SARS-CoV-2 infection, the new coronavirus causing the COVID-19 pandemic, was hindered due to the restrictions issued to avoid proximity between people and to stop the rapid spread of the disease, which ultimately results in a hyperinflammatory cytokine storm that can cause death. Because periodontal disease is one of the most frequent inflammatory diseases of the oral cavity, various theories have emerged postulating periodontal disease as a risk factor for developing severe complications associated with COVID-19. This motivated various studies to integrate questions related to periodontal status. For the present work, we used a previously validated self-report, which is a useful tool for facilitating epidemiological studies of periodontal disease on a large scale. Methodology: A blinded case-control study with participants matched 1:1 by mean age (37.7 years), sex, tobacco habits and diseases was conducted. After the diagnostic samples for SARS-CoV-2 detection were taken in an ad hoc location at Guadalajara University, the subjects were interviewed using structured questionnaires to gather demographic, epidemiological and COVID-19 symptom information. The self-reported periodontal disease (Self-RPD) questionnaire included six questions, and subjects who met the criteria with a score ≥ 2 were considered to have periodontal disease. Results: In total, 369 participants were recruited, with 117 participants included in each group. After indicating the subjects who had self-reported periodontal disease, a statistically significant difference (p value ≤ 0.001) was observed, showing that self-reported periodontal disease (n = 95, 85.1%) was higher in SARS-CoV-2-positive individuals than in controls (n = 66, 56.4%), with an OR of 3.3 (1.8-6.0) for SARS-CoV-2 infection in people with self-reported periodontal disease. Cases reported a statistically higher median of symptoms (median = 7.0, Q1= 5.5, Q3 = 10.0) than controls (p value ≤ 0.01), and cases with positive self-RPD had a significantly (p value ≤ 0.05) higher number of symptoms (median = 8.0, Q1 = 6.0, Q3 = 10.0) in comparison with those who did negative self-RPD (median = 6.0, Q1 = 5.0, Q3 = 8.0). Conclusions: According to this study, self-reported periodontal disease could be considered a risk factor for SARS-CoV-2 infection, and these individuals present more symptoms.

Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2.

New vaccine design approaches, platforms, and immunization strategies might foster antiviral mucosal effector and memory responses to reduce asymptomatic infection and transmission in vaccinated individuals. Here, we investigated a combined parenteral and mucosal immunization scheme to induce local and serum antibody responses, employing the epitope-based antigens 3BT and NG19m. These antigens target the important emerging and re-emerging viruses PRRSV-2 and SARS-CoV-2, respectively. We assessed two versions of the 3BT protein, which contains conserved epitopes from the GP5 envelope protein of PRRSV-2: soluble and expressed by the recombinant baculovirus BacDual-3BT. On the other hand, NG19m, comprising the receptor-binding motif of the S protein of SARS-CoV-2, was evaluated as a soluble recombinant protein only. Vietnamese mini-pigs were immunized employing different inoculation routes: subcutaneous, intranasal, or a combination of both (s.c.-i.n.). Animals produced antigen-binding and neut1ralizing antibodies in serum and mucosal fluids, with varying patterns of concentration and activity, depending on the antigen and the immunization schedule. Soluble 3BT was a potent immunogen to elicit binding and neutralizing antibodies in serum, nasal mucus, and vaginal swabs. The vectored immunogen BacDual-3BT induced binding antibodies in serum and mucosae, but PRRSV-2 neutralizing activity was found in nasal mucus exclusively when administered intranasally. NG19m promoted serum and mucosal binding antibodies, which showed differing neutralizing activity. Only serum samples from subcutaneously immunized animals inhibited RBD-ACE2 interaction, while mini-pigs inoculated intranasally or via the combined s.c.-i.n. scheme produced subtle neutralizing humoral responses in the upper and lower respiratory mucosae. Our results show that intranasal immunization, alone or combined with subcutaneous delivery of epitope-based antigens, generates local and systemic binding and neutralizing antibodies. Further investigation is needed to evaluate the capability of the induced responses to prevent infection and reduce transmission.

Higiene oral deficiente como factor de riesgo de cáncer oral / Poor oral hygiene as a risk factor for oral cancer

Introducción: Los principales factores de riesgo con los que se asocia el carcinoma oral de células escamosas son el hábito de tabaco y alcohol. La inflamación también es un factor de riesgo importante en el desarrollo del cáncer, ésta posiblemente inducida por el acúmulo de bacterias que se refleja en la placa bacteriana (biofilm microbiano) y posterior cálculo dental debido a una higiene oral deficiente. Objetivo: Asociar la higiene oral deficiente como factor de riesgo del carcinoma oral de células escamosas. Material y métodos: Estudio de casos y controles en el que se utilizó el índice de higiene oral simplificado para biofilm y cálculo como instrumento de medida. Se registraron los hábitos de tabaco y alcohol. El riesgo fue estimado obteniendo Odds Ratio y la significancia estadística fue tomada con base a χ2. Resultados: La higiene oral deficiente con altos niveles de placa bacteriana fue identificada como factor de riesgo de carcinoma oral de células escamosas, los factores de riesgo conocidos (tabaco y alcohol) fueron también identificados en nuestra población; sin embargo, el riesgo fue menor en contraste con la higiene oral deficiente. Conclusión: La higiene oral deficiente es un factor de riesgo significativo que contribuye a la presencia de cáncer oral y puede ser mayor en comparación con el consumo de tabaco y alcohol.

Comparison of orosomucoid-1 immunoexpression and angiogenesis between oral squamous cell carcinoma cases with different histological grades.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignancy in this region, and thus, further elucidation of its tumoral mechanisms is important. One of the main roles of the acute-phase protein orosomucoid-1 (ORM1) is the promotion of angiogenesis, which is key for tumor nutrition and growth. AIM: Our aim was to evaluate the immunohistochemical expression of ORM1 and the angiogenic activity indicated by microvascular density (MVD) in OSCC samples according to histological grade. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections from 45 OSCC cases were submitted to immunohistochemistry: 25 were well-differentiated OSCC, 18 were moderately differentiated OSCC and 2 were poorly differentiated OSCC. ORM1 staining was evaluated by a semiquantitative method, and CD34-positive blood vessels were quantified to calculate the MVD. The results were statically analyzed. RESULTS: All cases exhibited immunoexpression of ORM1 and CD34. However, no significant differences were found between the expression of both markers among the histological grades. In addition, the presence of ORM1 in inflammatory cells and in the extracellular matrix was detected in most cases. CONCLUSION: These results suggest that the induction of angiogenesis is not the main role of ORM1 in OSCC and may be associated with the regulation of the immune/inflammatory response or the transport of protumoral molecules, such as sialyl-Lewis X or phorbol esters, which requires confirmation in future studies.

The Tissue Architecture of Oral Squamous Cell Carcinoma Visualized by Staining Patterns of Wheat Germ Agglutinin and Structural Proteins Using Confocal Microscopy.

OBJECTIVES: Tissue architecture and cell morphology suffer profound alterations during oral cancer and are important markers for its progression and outcome. For precise visualization of tissue architecture in oral cancer, we used confocal microscopy to examine the staining pattern of wheat germ agglutinin, a lectin that binds membrane glycoproteins, and the staining patterns of structural proteins. MATERIALS AND METHODS: Paraffin sections of oral squamous cell carcinoma were stained with fluorescently labeled wheat germ agglutinin and with antibodies against structural proteins, which were revealed by immunohistochemistry with tyramide signal amplification. RESULTS: Membrane localization of wheat germ agglutinin was markedly decreased in the basal layers and in regions of tumor invasion, accompanied by cytoplasmic redistribution of E-cadherin, ß-actin and syndecan-1. Wheat germ agglutinin staining clearly identified tumor clusters within the surrounding stroma, and tumor cells with elongated morphology. CONCLUSIONS: Our results suggest that the wheat germ agglutinin staining pattern is indicative of the degree of cell cohesion in oral squamous cell carcinoma, which decreases in basal layers and invasive tumor clusters with more migratory morphologies. Wheat germ agglutinin staining in combination with confocal microscopy could constitute, therefore, a valuable tool for the study of tissue architecture in oral cancer.

Epithelial-Mesenchymal Transition Associated with Head and Neck Squamous Cell Carcinomas: A Review.

Head and neck squamous cell carcinomas (HNSCCs) are aggressive, recurrent, and metastatic neoplasms with a high occurrence around the world and can lead to death when not treated appropriately. Several molecules and signaling pathways are involved in the malignant conversion process. Epithelial-mesenchymal transition (EMT) has been described in HNSCCs, a major type of aggressive carcinoma. EMT describes the development of epithelial cells into mesenchymal cells, which depends on several molecular interactions and signaling pathways that facilitate mesenchymal conversion. This is related to interactions with the microenvironment of the tumor, hypoxia, growth factors, matrix metalloproteinases, and the presence of viral infections. In this review, we focus on the main molecules related to EMT, their interactions with the tumor microenvironment, plasticity phenomena, epigenetic regulation, hypoxia, inflammation, their relationship with immune cells, and the inhibition of EMT in the context of HNSCCs.

Perilipin 1 and adipophilin immunoexpression suggests the presence of lipid droplets in tooth germ, ameloblastoma, and ameloblastic carcinoma.

BACKGROUND: Increased lipogenesis and lipid droplet accumulation are observed in diverse tumors, and these processes are associated with poor prognosis in several tumors, representing potential therapeutic targets. The presence of lipid droplets in odontogenic tissues and/or tumors is unknown. METHODS: Immunohistochemistry for perilipin 1 and adipophilin was performed in 12 human tooth germs (TG), 27 conventional ameloblastoma (AM), and 8 ameloblastic carcinoma (AC) samples. Cytoplasmic staining was analyzed using an immunoreactive score (IRS), and the results were compared for the TG, AM, and AC samples by Kruskal-Wallis test followed by Dunn's post-test and confirmed by Mann-Whitney U test. RESULTS: Perilipin 1 was negative in 91.7% of the TG samples, positive in 48.2% of the AM samples, and positive in 87.5% of the AC samples. Adipophilin was positive in 100% of the TG samples, 92.6% of the AM samples, and 100% of the AC samples. The perilipin 1 and adipophilin IRS revealed statistically significant differences between the TG, AM, and AC samples (p = .007 and p = .018, respectively). The perilipin 1 levels among the TG and AC samples were statically significant (**p = .0085), as well as the adipophilin levels when TG and AM samples were compared (**p < .0029). CONCLUSIONS: Adipophilin exhibits significant activity in human tooth development. The immunoexpression of perilipin 1 and adipophilin in the AM and AC samples suggests the presence of lipid droplets, providing further evidence of metabolic alterations in these tumors. Additional studies with larger samples and alternative techniques are necessary to confirm these findings.

Expression of caveolin-1 in tooth germ, ameloblastoma and ameloblastic carcinoma / Expresión de caveolina-1 en germen dental ameloblastoma y carcinoma ameloblástico

Background: The caveolin-1 protein (structural component of membrane caveolae) plays important roles in sev-eral biological functions, such as endocytosis, cell adhesion, and cell signaling. However, this protein has been as-sociated with mechanisms of tumorigenesis in several neoplasms. The expression patterns and roles of caveolin-1in the oral epithelium and in embryonic and odontogenic tumor tissues are still unclear.Material and Methods: The expression of caveolin-1 was evaluated in samples of the normal gingival epithelium(n=7), human tooth germ (TG) (n=12), ameloblastoma (AM) (n=83), and ameloblastic carcinoma (AC) (n=9) byimmunohistochemistry. Additionally, AM samples were analyzed by qRT-PCR and Western blot.Results: Most TG (91.7%), AM (73.5%) and AC (100%) samples showed diverse patterns of immunohistochemicalpositivity for caveolin-1, while only one gingival sample was positive. The transcript levels of cav-1 were signifi-cantly upregulated by 14.9-fold in AM tissue (P = 0.0014) compared to those in normal gingival epithelial tissue,as shown by qRT-PCR. Presence of caveolin-1 protein was confirmed by Western blot analysis. The caveolin-1immunoexpression patterns throughout the stages of TG show its importance during odontogenesis.Conclusions: The overexpression of caveolin-1 in AM and AC compared to its expression in normal gingivalepithelium (adult tissue) suggests a possible role of caveolin-1 in protumoral events, but due to the similar immu-noexpression observed in AM and AC, caveolin-1 may not necessarily participate in the malignant transformationprocess. However, future studies are needed to clarify and confirm these hypotheses.(AU)

Recent Biomarkers for Monitoring the Systemic Fluoride Levels in Exposed Populations: A Systematic Review.

Fluorides are compounds that can be found in the minerals of soil with volcanic rocks. Different populations are exposed to high levels of fluorides through drinking water that, due to their chronic intake, cause several types of damage to health. Nails and hair, denominated as recent biomarkers, have been employed for monitoring systemic fluoride from long-term exposure to fluorides. The aim of this study was to perform a systematic review of the use of recent biomarkers for monitoring systemic fluoride levels in exposed populations and verify their validity in the measurement of the fluorine (F-) concentration within the body. A digital search was performed in the databases PubMed/Medline, Springer Link, Cochrane, and Scopus of original articles that employed recent biomarkers for monitoring systemic F-. Seventeen articles were included in this analysis; the recorded variables were the F- amount in each assessed biomarker, source of exposure, and total daily fluoride intake (TDFI). TDFI was associated with F- in nails and hair, as well as the exposure through drinking water. In conclusion, recent biomarkers are adequate for monitoring the systemic fluoride levels by evaluating the chronic/subchronic exposure through different sources, mainly drinking water, considering nails better than hair for this purpose.

Primordial odontogenic tumor: A systematic review

BACKGROUND: The primordial odontogenic tumor (POT) is a recently described benign entity with histopathological and immunohistochemical features suggesting its origin during early odontogenesis. AIM: To integrate the available data published on POT into a comprehensive analysis to better define its clinicopathological and molecular features. MATERIAL AND METHODS: An electronic systematic review was performed up to September 2019 in multiple databases. RESULTS: A total of 13 publications were included, representing 16 reported cases and 3 molecular studies. The mean age of the affected patients was 11.6 years (range 2-19), with a slight predominance in males (56.25%). The posterior mandible was the main location (87.5%), with only two cases affecting the posterior maxilla. All cases appeared as a radiolucent lesion in close relationship to an unerupted tooth. Recurrences have not been reported to date. Microscopically, POT comprises fibromyxoid tissue with variable cellularity surrounded by a cuboidal to columnar odontogenic epithelium but without unequivocal dental hard tissue formation. A delicate fibrous capsule surrounds (at least partially) the tumor. The epithelial component shows immunohistochemical positivity for am-elogenin, CK19, and CK14, and variable expression of Glut-1, Galectin-3 and Caveolin-1, Vimentin, p-53, PITX2, Bcl-2, Bax and Survivin; the mesenchymal tissue is positive for Vimentin, CD90, p-53, PITX2, Bcl-2, Bax, and Survivin, and the subepithelial region exhibits the strong expression of Syndecan-1 and CD34. The Ki-67 index is low (<5%). The negative or weak expression of dentinogenesis-associated genes could explain the inhibition of dentin and subsequent enamel formation in this neoplasm. CONCLUSION: POT is an entity with a well-defined clinicopathological, immunohistochemical and molecular profile that must be properly diagnosed and differentiated from other odontogenic lesions and treated consequently

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