Abstract Associations between the WNT5A rs566926 variant and non-syndromic orofacial cleft (NSOC) have been reported in different populations. Objective This study aimed to investigate the role of the rs566926 single nucleotide polymorphism (SNP) in WNT5A and its interactions with SNPs in BMP4, FGFR1, GREM1, MMP2, and WNT3 in the occurrence of NSOC in a Brazilian population. Methodology A case-control genetic association study was carried out involving participants from four regions of Brazil, totaling 801 patients with non-syndromic cleft lip with or without cleft palate (NSCL±P), 273 patients with cleft palate only (NSCPO), and 881 health volunteers without any congenital condition (control). Applying TaqMan allelic discrimination assays, we evaluated WNT5A rs566926 in an ancestry-structured multiple logistic regression analysis, considering sex and genomic ancestry as covariates. Interactions between rs566926 and variants in genes involved in the WNT5A signaling pathway (BMP4, FGFR1, GREM1, MMP2, and WNT3) were also explored. Results WNT5A rs566926 was significantly associated with an increased risk of NSCL±P, particularly due to a strong association with non-syndromic cleft lip only (NSCLO), in which the C allele increased the risk by 32% (OR: 1.32, 95% CI: 1.04–1.67, p=0.01). According to the proportions of European and African genomic ancestry, the association of rs566926 reached significant levels only in patients with European ancestry. Multiple interactions were detected between WNT5A rs566926 and BMP4 rs2071047, GREM1 rs16969681 and rs16969862, and FGFR1 rs7829058. Conclusion The WNT5A rs566926 polymorphism was associated with NSCL±P, particularly in individuals with NSCLO and high European ancestry. Epistatic interactions involving WNT5A rs566926 and variants in BMP4, GREM1, and FGFR1 may contribute to the risk of NSCL±P in the Brazilian population. WNTA WNT rs rs56692 nonsyndromic non syndromic (NSOC populations SNP (SNP BMP FGFR GREM MMP2 MMP population casecontrol case control Brazil 80 NSCLP , NSCL P (NSCL±P) 27 NSCPO, NSCPO (NSCPO) 88 control. . (control) assays ancestrystructured structured analysis covariates (BMP4 explored NSCLO, (NSCLO) 32 OR (OR 132 1 1.32 95 CI 104167 04 67 1.04–1.67 p=0.01. p001 p p=0.01 0 01 p=0.01) rs2071047 rs1696968 rs16969862 rs7829058 rs5669 8 (NSCL±P 2 (NSCPO (control (BMP (NSCLO 3 13 1.3 9 10416 6 1.04–1.6 p00 p=0.0 rs207104 rs169696 rs1696986 rs782905 rs566 1. 1041 1.04–1. p0 p=0. rs20710 rs16969 rs169698 rs78290 rs56 104 1.04–1 p=0 rs2071 rs1696 rs7829 rs5 10 1.04– p= rs207 rs169 rs782 1.04 rs20 rs16 rs78 1.0 rs2 rs1 rs7

RESUMO Objetivo: Relatar o caso de uma jovem que apresentava um fenótipo grave de displasia mandibuloacral tipo A (MADA) caracterizado por alterações osteolíticas proeminentes e defeitos ectodérmicos, associados a uma rara mutação homozigótica missense no gene LMNA (c.1579C>T). Descrição do caso: Uma menina de seis anos foi avaliada durante hospitalização apresentando os seguintes sinais dismórficos: alopecia subtotal, fácies dismórfica com olhos proeminentes, micrognatia e retrognatia acentuada, nariz pequeno e adunco, dentes apinhados e lábios finos, lipodistrofia generalizada, ombros estreitos e inclinados, rigidez articular e reabsorção óssea nas falanges terminais. Ao exame dermatológico, observou-se pele atrófica, perda da elasticidade cutânea, hiperceratose, calcinose dérmica e manchas hiperpigmentadas e hipocrômicas. Exames radiológicos realizados mostraram ausência de côndilos mandibulares bilaterais, reabsorção da clavícula com massa óssea amorfa local confluindo com as escápulas, articulações do ombro com subluxação e displasia óssea severa, com displasia coxofemoral, osteopenia e calcificações subcutâneas. Comentários: MADA é uma doença autossômica recessiva rara causada por mutações no gene LMNA. Caracteriza-se por deformidades craniofaciais, anomalias esqueléticas, alterações cutâneas, lipodistrofia em determinadas regiões do corpo e envelhecimento precoce. MADA típica é causada pela mutação p.R527H no gene LMNA. No entanto, a análise molecular realizada com células epiteliais orais obtidas da paciente mostrou a mutação rara c.1579C>T, p. R527C no exon 9 do gene LMNA. Esta é a sexta família identificada com essa mutação descrita na literatura. Objetivo (MADA ectodérmicos c.1579C>T. c1579CT cCT c.1579C>T . c 1579C T C (c.1579C>T) dismórficos subtotal acentuada adunco finos generalizada inclinados terminais dermatológico observouse observou se atrófica cutânea hiperceratose hipocrômicas bilaterais escápulas severa coxofemoral subcutâneas Comentários Caracterizase Caracteriza craniofaciais esqueléticas cutâneas precoce pR527H pRH p R527H R H entanto RC literatura CT (c.1579C>T pR RH

ABSTRACT Objective: To report the case of a girl presenting a severe phenotype of mandibuloacral dysplasia type A (MADA) characterized by prominent osteolytic changes and ectodermal defects, associated with a rare homozygous LMNA missense mutation (c.1579C>T). Case description: A 6-year-old girl was evaluated during hospitalization exhibiting the following dysmorphic signs: subtotal alopecia, dysmorphic facies with prominent eyes, marked micrognathia and retrognathia, small beaked nose, teeth crowding and thin lips, generalized lipodystrophy, narrow and sloping shoulders, generalized joint stiffness and bone reabsorption in the terminal phalanges. In dermatological examination, atrophic skin, loss of cutaneous elasticity, hyperkeratosis, dermal calcinosis, and hyperpigmented and hypochromic patches were observed. Radiology exams performed showed bilateral absence of the mandibular condyles, clavicle resorption with local amorphous bone mass confluence with the scapulae, shoulder joints with subluxation and severe bone dysplasia, hip dysplasia, osteopenia and subcutaneous calcifications. Comments: MADA is a rare autosomal recessive disease caused by mutations in LMNA gene. It is characterized by craniofacial deformities, skeletal anomalies, skin alterations, lipodystrophy in certain regions of the body and premature ageing. Typical MADA is caused by the p.R527H mutation in the LMNA gene. However, molecular analysis performed from oral epithelial cells obtained from the patient showed the rare mutation c.1579C>T, p. R527C in the exon 9 of LMNA. This is the sixth family identified with this mutation described in the literature. Objective (MADA defects c.1579C>T. c1579CT cCT c.1579C>T . c 1579C T C (c.1579C>T) description 6yearold yearold 6 year old signs alopecia eyes retrognathia nose lips shoulders phalanges examination elasticity hyperkeratosis calcinosis observed condyles scapulae calcifications Comments gene deformities anomalies alterations ageing pR527H pRH p R527H R H However RC literature CT (c.1579C>T pR RH

Abstract Objectives This study aimed to assess the prevalence of oral lesions in patients living with HIV infection and their association with CD4 count, viral load, and antiretroviral therapy in patients with HIV. Methods A cross-sectional study was conducted on a sample of 161 patients attending the… All the patients were examined for their oral lesions, current CD4 counts, type, and duration of the therapy. Data analyses were carried out using Chi-Square, Student T/Mann-Whitney, and logistic regression tests. Results Oral lesions were observed in 58.39% of patients with HIV. Periodontal disease with 78 (48.45%) or without mobility 79 (49.07%) was observed more frequently, followed by hyperpigmentation of oral mucosa 23 (14.29%), Linear Gingival Erythema (LGE) 15 (9.32%), candidiasis pseudomembranous 14 (8.70%). Oral Hairy Leukoplakia (OHL) was observed only in 3 (1.86%). A relationship between periodontal disease with dental mobility and smoking was found (p = 0.04), as well duration of treatment (p = 1.53e-3) and age (p = 0.02). Hyperpigmentation was related to race (p = 0.01) and smoking (p = 1.30e-6). CD4 count, CD4:CD8 ratio, viral load, or type of treatment were not associated with oral lesions. Logistic regression showed that the duration of treatment has a protective effect on the periodontal disease with dental mobility (OR = 0.28 [−2.27 to −0.25]; p-value = 0.03), independent of age or smoking. To hyperpigmentation, the best model included smoking (OR = 8.47 [1.18-3.10], p = 1.31e-5), without race or type and duration of treatment. Conclusion Among HIV patients undergoing antiretroviral treatment, oral lesions can be observed, predominantly periodontal disease. Pseudomembranous candidiasis and oral hairy leukoplakia were also observed. No relationship was found between associated oral manifestations in HIV patients and the start of the treatment, TCD4+ and TCD8+ cell count, TCD4:TCD8 ratio, or viral load. The data indicate that there is a protective effect of duration of treatment with relation to periodontal disease with mobility and that hyperpigmentation seems to be more related to smoking than type and duration of treatment. Level of evidence Level 3 (OCEBM Levels of Evidence Working Group*. "The Oxford 2011 Levels of Evidence"). CD count load crosssectional cross sectional 16 counts ChiSquare, ChiSquare Chi Square, Square Chi-Square T/MannWhitney, TMannWhitney T/Mann Whitney, T Mann Whitney T/Mann-Whitney tests 5839 58 39 58.39 7 48.45% 4845 48 45 (48.45% 49.07% 4907 49 07 (49.07% frequently 2 14.29%, 1429 14.29% , 29 (14.29%) LGE (LGE 1 9.32%, 932 9.32% 9 32 (9.32%) 8.70%. 870 8.70% . 8 70 (8.70%) OHL (OHL 1.86%. 186 1.86% 86 (1.86%) 0.04, 004 0.04 0 04 0.04) 1.53e3 153e3 e 1.53e 53e 1.53e-3 0.02. 002 0.02 02 0.02) 0.01 001 01 1.30e6. 130e6 1.30e 6 30e 1.30e-6) CD4CD8 CDCD CD8 CD4:CD ratio OR 028 28 0.2 −2.27 227 27 [−2.2 −0.25 025 25 −0.25] pvalue value 0.03, 003 0.03 03 0.03) 847 47 8.4 1.183.10, 118310 1.18 3.10 18 10 [1.18-3.10] 1.31e5, 131e5 1.31e 5 31e 1.31e-5) TCD4 TCD TCD8 TCD4TCD8 TCDTCD TCD4:TCD OCEBM Group Group* 201 Evidence. Evidence") MannWhitney T/MannWhitney TMann 583 58.3 48.45 484 4 (48.45 49.07 490 (49.07 142 14.29 (14.29% 93 9.32 (9.32% 87 8.70 (8.70% 1.86 (1.86% 00 0.0 53e3 153e 1.53e- 30e6 1.30e6 130e 1.30e-6 CD4CD 0. −2.2 22 [−2. −0.2 84 8. 183 1.183.10 11831 118 1.1 310 3.1 [1.18-3.10 31e5 1.31e5 131e 1.31e-5 TCD4TCD 20 Evidence" 58. 48.4 (48.4 49.0 (49.0 14.2 (14.29 9.3 (9.32 8.7 (8.70 1.8 (1.86 1.30e- −2. [−2 −0. 1.183.1 1183 11 1. 31 3. [1.18-3.1 1.31e- 48. (48. 49. (49. 14. (14.2 9. (9.3 (8.7 (1.8 −2 [− −0 1.183. [1.18-3. (48 (49 (14. (9. (8. (1. − [ 1.183 [1.18-3 (4 (14 (9 (8 (1 [1.18- ( [1.18 [1.1 [1. [1

Abstract Hypertrichosis and dental anomalies may occur alone or in combination in the spectrum of many syndromes. To identify genetic entities characterized by hypertrichosis and dental anomalies, a search was performed in the Mendelian Inheritance in Man database with the terms “hypertrichosis” or “hirsutism” and “tooth” or “dental abnormalities.” Nondependent androgen metabolism disturbances were classified as hypertrichosis. Genetic entities with hypertrichosis and dental anomalies were included in the study. Additional searches were performed in the PubMed and Orphanet databases, when necessary, in order to include data from scientific articles. An integrative analysis of the genes associated with the identified syndromes was conducted using STRING to characterize biological processes, pathways, and interactive networks. The p-values were subjected to the false discovery rate for the correction of multiple tests. Thirty-nine syndromes were identified, and dental agenesis was the most frequent dental anomaly present in 41.02% (n = 16) of the syndromes. Causative genes were identified in 33 out of 39 genetic syndromes. Among them, 39 genes were identified, and 38 were analyzed by STRING, which showed 148 biological processes and three pathways that were statistically significant. The most significant biological processes were the disassembly of the nucleosome (GO:0006337, p = 1.09e-06), chromosomal organization (GO:0051276, p = 1.09e-06) and remodeling of the chromatin (GO: 0006338, p = 7.86e-06), and the pathways were hepatocellular carcinoma (hsa05225, p = 5.77e-05), thermogenesis (hsa04714, p = 0.00019), and cell cycle (hsa04110, p = 0.0433). Our results showed that the identification of hypertrichosis and dental anomalies may raise the suspicion of one of the thirty-nine syndromes with both phenotypes. “hypertrichosis hirsutism “hirsutism tooth “tooth abnormalities. abnormalities study databases necessary articles networks pvalues values tests Thirtynine Thirty nine 4102 41 02 41.02 n 16 3 them 14 GO0006337, GO0006337 GO 0006337, 0006337 (GO:0006337 1.09e06, 109e06 e 1.09e 06 , 1 09e GO0051276, GO0051276 0051276, 0051276 (GO:0051276 1.09e06 1.09e-06 (GO 0006338 7.86e06, 786e06 7.86e 7 86e 7.86e-06) hsa05225, hsa05225 hsa (hsa05225 5.77e05, 577e05 5.77e 05 5 77e 5.77e-05) hsa04714, hsa04714 (hsa04714 0.00019, 000019 0.00019 0 00019 0.00019) hsa04110, hsa04110 (hsa04110 0.0433. 00433 0.0433 . 0433 0.0433) thirtynine thirty phenotypes 410 4 41.0 GO000633 000633 (GO:000633 09e06 109e0 109e GO005127 005127 (GO:005127 1.09e0 1.09e-0 86e06 7.86e06 786e0 786e 7.86e-06 hsa0522 (hsa0522 77e05 5.77e05 577e0 577e 5.77e-05 hsa0471 (hsa0471 00001 0.0001 0001 hsa0411 (hsa0411 0043 0.043 043 41. GO00063 00063 (GO:00063 09e0 GO00512 00512 (GO:00512 1.09e- 86e0 7.86e0 7.86e-0 hsa052 (hsa052 77e0 5.77e0 5.77e-0 hsa047 (hsa047 0000 0.000 000 hsa041 (hsa041 004 0.04 04 GO0006 0006 (GO:0006 GO0051 0051 (GO:0051 7.86e- hsa05 (hsa05 5.77e- hsa04 (hsa04 0.00 00 0.0 GO000 (GO:000 GO005 005 (GO:005 hsa0 (hsa0 0. GO00 (GO:00 (hsa GO0 (GO:0

ABSTRACT Objective To evaluate the effect of the COVID-19 impacts on the activities of researchers in the field of Oral Medicine (OM) and Oral Pathology (OP). To assess the research activities and training of human resources by Brazilian productivity fellows in research (BPFR) in OM and OP in the COVID-19 Era. Material and Methods Thirty-six BPFR in OM and OP areas, funded by National Council for Scientific and Technological Development (CNPq), received a virtual structured questionnaire by e-mail, on the Google Forms (Google®) platform, with questions regarding research activities and training of human resources (supervision of undergraduate and postgraduate students), during the COVID-19 pandemic. From the thirty-six BPFR in OM and OP, twenty-seven (75.0%) answered the questionnaire. Results Most of them were males (n=20; 74.1%) and were distributed in four Brazilian regions and ten states of the federation, including the Federal District. Twenty-four (88.9%) BPFR reported having suspended clinical activities, while sixteen (59.3%) answered that histopathology practices are suspended. Twenty-five (92.6%) BPFR mentioned difficulties in conducting research projects and 55.5% stated having no difficulties in the supervision of undergraduates, master’s and PhD students. Conclusion The current scenario may significantly impact the diagnosis of oral diseases in Brazil. Moreover, a decrease in the scientific production of BPFR in OM and OP in the coming years is also considered.

Abstract: Kawasaki disease (KD) is a vasculitis with predilection for coronary arteries. Due to a lack of reliable confirmatory laboratory tests, the diagnosis of KD is based on a characteristic pattern of clinical findings that appear in a typical temporal sequence. The diagnostic criteria have been periodically modified and the American Heart Association has proposed the most recent guidelines for its diagnosis. However, patients may have incomplete or atypical forms of KD and diagnosis can often be difficult. Because oropharyngeal manifestations are a common and important feature for diagnosing KD and recent studies have hypothesized a possible association between KD and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in this review we highlight the importance of dentists in the diagnosis of KD and its potential association with SARS-CoV-2.

Abstract This study aimed to analyze the 100 most-cited papers in the field of oral medicine and pathology over time, identifying the areas of more intense research. Papers in journals of oral medicine and pathology were identified using the Web of Science database. The specified research period was between 1900 and 2019. Descriptive statistics was used to analyze the data. Pearson’s correlation analysis was used to explore the relationships among Web of Science citations, Dimensions citations, and Altmetric Attention Score. The number of citations of an article in the top 100 most-cited papers published in 1953 or later ranged from 541 to 3623. The papers were published in 47 different journals. The New England Journal of Medicine, American Cancer Society, and Nature Genetics published the most papers. Authors from 18 different countries published papers on head and neck cancer, craniofacial congenital anomalies, and osteonecrosis. Most of the papers were laboratory and descriptive studies. A correlation analysis showed a strong correlation only between Web of Science and Dimensions citations. In sum, although non-specific journals for pathology and oral medicine published the majority of the 100 most-cited papers, this biometric citation study show that head and neck cancer was the issue with the most citations. Together, these results make an important scientific contribution by providing a historical perspective on the research carried out.

Resumo Objetivos: investigar a prevalência de anomalias dentárias na dentição decídua completa de crianças com FL/PNS. Métodos: este estudo incluiu 75 crianças com FL/PNS e 286 controles saudáveis. Em ambos os grupos as crianças tinham dentição decídua com idade variando de 4 a 6 anos. Exame clínico, radiografias panorâmicas e periapicais foram realizadas e anomalias dentárias de número e forma foram consideradas. Resultados: houve maior prevalência de anomalias dentárias no grupo caso, comparado ao grupo controle. Ao todo 42 anomalias dentárias foram identificadas, 25,33% no grupo caso e 8,04% no grupo controle (p<0,001). Houve maior frequência de anomalias dentárias na FL/PNS (47,36%), seguida da fissura labial não sindrômica (31,57%) e da fissura palatina não sindrômica (21,05%). A ocorrência de agenesia (p= 0,005) e geminação (p=0,029) foram maiores no grupo caso. Conclusão: a ocorrência de agenesia e geminação dentária foram mais frequentes no grupo caso e pode contribuir para a definição de subfenótipos de fissuras orais.

Abstract Objectives: to investigate the prevalence of dental anomalies in complete deciduous dentition of children with NSCL/P. Methods: this study included 75 children with NSCL/P and 286 healthy control. In both groups the children had deciduous dentition with ages varying from 4 to 6 years. Clinical examination, panoramic and periapical radiographies were performed and dental anomalies of number and shape were considered. Results: there was a higher prevalence of dental anomalies in the case group, compared to the control group. In all, 42 dental anomalies were identified, 25.33% in the case group and 8.04% in control group (p<0.001). Therewas a higher frequency of dental anomalies in NSCL/P (47.36%), followed by non-syndromic cleft lip (31.57%) and non-syndromic cleft palate (21.05%). The occurrence of agenesis (p= 0.005) and twinning (p = 0.029) were higher in the case group. Conclusions: the occurrence of agenesis and dental twinning was more frequent in the case group and may contribute to the definition of oral cleft subphenotype.

BACKGROUND Oxidative stress is responsible for generating DNA lesions and the 8-oxoguanine (8-oxoG) is the most commonly lesion found in DNA damage. When this base is incorporated during DNA replication, it could generate double-strand DNA breaks and cellular death. MutT enzyme hydrolyzes the 8-oxoG from the nucleotide pool, preventing its incorporation during DNA replication. OBJECTIVES To investigate the importance of 8-oxoG in Leishmania infantum and L. braziliensis, in this study we analysed the impact of heterologous expression of Escherichia coli MutT (EcMutT) enzyme in drug-resistance phenotype and defense against oxidative stress. METHODS Comparative analysis of L. braziliensis and L. infantum H2O2 tolerance and cell cycle profile were performed. Lines of L. braziliensis and L. infantum expressing EcMutT were generated and evaluated using susceptibility tests to H2O2 and SbIII, cell cycle analysis, γH2A western blotting, and BrdU native detection assay. FINDINGS Comparative analysis of tolerance to oxidative stress generated by H2O2 showed that L. infantum is more tolerant to exogenous H2O2 than L. braziliensis. In addition, cell cycle analysis showed that L. infantum, after treatment with H2O2, remains in G1 phase, returning to its normal growth rate after 72 h. In contrast, after treatment with H2O2, L. braziliensis parasites continue to move to the next stages of the cell cycle. Expression of the E. coli MutT gene in L. braziliensis and L. infantum does not interfere in parasite growth or in susceptibility to SbIII. Interestingly, we observed that L. braziliensis EcMutT-expressing clones were more tolerant to H2O2 treatment, presented lower activation of γH2A, a biomarker of genotoxic stress, and lower replication stress than its parental non-transfected parasites. In contrast, the EcMutT is not involved in protection against oxidative stress generated by H2O2 in L. infantum. MAIN CONCLUSIONS Our results showed that 8-oxoG clearance in L. braziliensis is important to avoid misincorporation during DNA replication after oxidative stress generated by H2O2.