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Objectives JDM is a serious autoimmune and complex genetic disease. Another autoimmune genetic disease, type 1 diabetes (T1D), has been observed for significantly increased prevalence in families with JDM, while increased JDM risk has also been observed in T1D cases. This study aimed to study whether these two autoimmune diseases, JDM and T1D, share common genetic susceptibility. Methods From 169 JDM families, 121 unrelated cases with European ancestry (EA) were identified by genome-wide genotyping, principal component analysis and identical-by-descent (IBD) analysis. T1D genetic risk score (GRS) were calculated in these cases and were compared with 361 EA T1D cases and 1943 non-diabetes EA controls. A total of 113 cases of the 121 unrelated European cases were sequenced by whole exome sequencing. Results We observed increased T1D GRS in JDM cases (P = 9.42E-05). Using whole exome sequencing, we uncovered the T1D genes, phospholipase B1, cystic fibrosis transmembrane conductance regulator, tyrosine hydroxylase, CD6 molecule, perforin 1 and dynein axonemal heavy chain 2, potentially associated with JDM by the burden test of rare functional coding variants. Conclusion Novel mechanisms of JDM related to these T1D genes are suggested by this study, which may imply novel therapeutic targets for JDM and warrant further study.

Approximately 20–30% of children presenting with acquired inflammatory demyelinating syndromes (ADS) have multiple sclerosis (MS). Another 30% harbor serum antibodies against myelin oligodendrocyte glycoprotein and are referred to as having MOG-associated disease (MOGAD). While MS and MOGAD can have similar features, differences in response to immune therapies point to distinct underlying immune mechanisms. To assess potentially distinct immune mechanisms underlying MS and MOGAD, we applied proteogenomics to high quality cryopreserved peripheral blood mononuclear cells collected from patients with ADS prior to institution of immune therapy, as well as from healthy controls. CITE-Seq profiling was applied to a total of 92,716 single cells with equal contribution from 24 children (6 healthy donors; 6 with ADS but neither MS or MOGAD; 6 with MOGAD; and 6 with MS, ascertained with long-term follow-up). Analysis revealed a pan-ADS enrichment of atypical (CD11c+) B cells compared to healthy controls. Children with MS were distinguished from children with MOGAD by MS-specific enrichments of checkpoint-molecule (TIGIT and CD137)-expressing CD8 memory T cells, STAT4+ Th1 CD4 memory T cells and CD56dim/CD16+ NK cells. Overall, our study identifies distinct features of circulating cellular immune profiles that may serve to distinguish children with MS and MOGAD, and provides novel insights into early immune mechanisms that may be involved in each of these conditions.

Uterine natural killer cells (uNKs) are critical mediators of pregnancy success, but how aberrancies in uNK survival or differentiation underpin pregnancy complications is unknown. To improve our understanding of normal and abnormal uNK biology, we studied 1) uNKs in uterus transplant (UTx) recipients at high risk for pregnancy complications and 2) uNK survival after exposure to pharmacologic immunosuppression in vitro. To address the first question, we analyzed uNKs isolated from endometrial biopsies of healthy controls (n=3) or UTx recipients (n=5) using scRNA-seq. In healthy controls, CD103-expressing uNK3 cells were the dominant uNK subset (30% of all uNK cells). In contrast, uNK1 cells were the most frequent (30%) in the majority of UTx recipients. This dominance of uNK1 cells in UTx recipients did not appear to arise only from loss of uNK3 cells, as the uNK1 transcriptional signature was abnormally upregulated in immature proliferating uNKs. Next, we used multiparameter flow cytometry to study single-cell suspensions of whole endometrium from deceased organ donors (n=4) that were cultured for one week with or without the calcineurin inhibitor FK506. Although FK506 significantly impaired the survival of CD103+ uNK3 cells in vitro, there was no evidence of uNK1 enhancement. Instead, FK506 appeared to selectively deplete CD39+ cells – a marker currently used to identify human decidual NK1 cells. Altogether, these results demonstrate that the distribution of uNK subsets is often altered in UTx recipients, and that FK506 can impact the survival of specific uNK subsets. Identification of the additional factors which impact uNK differentiation and survival will be necessary to understand the genesis of pregnancy complications. Supported by NIH/NIAID (R01 AI 145905) University of Pennsylvania Institute for Immunology

Uterine NK cells (uNK) are a distinct immune population which influence pregnancy outcome. While murine studies have suggested that tissue-resident uNKs predominate in virgin endometrium, the origin of uNKs in humans is unknown. To define subsets of uterine NKs in humans and determine their developmental origin, we performed single-cell RNA-sequencing on CD56+ uNKs sorted from endometrial biopsies of 4 healthy controls (HCs) (17,146 cells) and 5 uterus transplant (UTx) recipients (30,351 cells). SNP polymorphisms and HLA alleles were used to identify cells of donor (tissue-resident) or recipient (peripheral) origin in UTx recipients. Developmental trajectories were built with Monocle v.3.0. Ten major clusters were identified in HCs, with 48% of endometrial NK cells (eNKs) occupying 3 clusters (eNK1–3) that shared gene signatures with known human decidual NK cell subsets (dNK1–3). Pseudotime analysis revealed that the eNK1–3 clusters arose from proliferating subsets and were less mature than cytotoxic uNKs expressing ZEB2, TBX21, and FCGR3A (CD16). uNKs from UTx recipients were similarly distributed across the clusters, with a trend towards fewer cells in the FCGR3A-expressing mature subset. Notably, recipient-derived uNKs dominated all uNK subsets within four months post-transplant but became less frequent in UTx recipients >1 year after transplant (95% vs. 72%; early vs. late). The proportion of donor-derived to recipient-derived cells remained constant across subsets in all UTx recipients. In contrast to mouse models, our study suggests that human uNKs derive primarily from blood-borne peripheral immigrants and that environmental factors influence uNK differentiation more than genotype or developmental origin.

The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.

Avaliou-se o efeito da ivermectina sobre o parênquima testicular através da produção espermática diária e da eficiência da espermatogênese em ratos Wistar adultos tratados com diferentes dosagens (200, 400 e 600µg/kg). Pela avaliação histomorfométrica, o parênquima testicular e o processo espermatogênico dos ratos Wistar não sofreram qualquer efeito deletério da aplicação de ivermectina, o que foi confirmado pela manutenção da produção espermática diária por testículo, pelo rendimento intrínseco da espermatogênese (PED/g/t) e pela manutenção da estrutura do parênquima testicular. Com base nos resultados quantitativos e qualitativos da espermatogênese, é possível concluir que a ivermectina não tem efeito tóxico-degenerativo sobre o parênquima testicular de ratos Wistar adultos.

BACKGROUND: Fine needle aspiration cytology (FNAC) is an important technique in the diagnosis of oral and maxillofacial conditions. The purpose of the present paper is to report a case of oral metastasis of breast carcinoma diagnosed by FNAC. CASE: A 45-year-old, black woman was referred for evaluation of symptomatic swelling in the left mandible. The medical history revealed that the patient had undergone extensive surgery to remove a lobular carcinoma. She had finished chemotherapy treatment about 5 months earlier. Due to the main diagnostic considerations of metastatic and inflammatory disease, FNAC was performed. The cytologic picture was consistent with a metastatic glandular neoplasm. CONCLUSION: FNAC is a safe, reliable, cost-effective and easy procedure and sometimes eliminates the need for open biopsy.

Submitted by Mario BC (mario@bc.ufrpe.br) on 2018-05-03T15:03:06Z No. of bitstreams: 1 Fernanda Mafra Caju.pdf: 1734506 bytes, checksum: 2a98e11a55cf05a64d5657f7e0a37ca6 (MD5) Made available in DSpace on 2018-05-03T15:03:06Z (GMT). No. of bitstreams: 1 Fernanda Mafra Caju.pdf: 1734506 bytes, checksum: 2a98e11a55cf05a64d5657f7e0a37ca6 (MD5) Previous issue date: 2012-07-31 Tadalafil is a 5(PDE5) fosfodiesterases inhibitor type that was created for tratament of erectile dysfunction in men, however, until nowadays, the information is conflicting regarding the side effects of these inhibitors on testicular function.To study the effects of tafalafil on testicular function it was performed an in-vivo study, where it was used 15 male and adult Swiss Webster mice (Mus musculus). The animals were divided in control group (n=8) and treated group (n=7). The animals in treated group received 25mg/kg of tadalafil, daily for 30 days by intraperitoneal via (IP) while, control group animals received the same sterile vehicle by the same way. At the end of the experiment, the animals were heparinized, anesthetized with ketamine and xylazine and euthanized by deep anesthesia. Liver, spleen, kidney, prostate, seminal vesicles, testes and epididymides were collected and weighed to be compared between groups, testicular fragments were fixed with Glutaraldehyde in sodium phosphate buffer, 0.01 M and pH 7.4. The testicular fragments were routinely processed for embedding in plastic resin based on glycol methacrylate and analized by hystomorphometry and electronic microscopy. Plasmatic testosterone was determined by ELISA test after the cardiac puncture and obtaining of total blood. According with the results, the tadalafil dosage and period utilized does not produced negative effects on the testicular parenchyma, just at the electronic microscopy that was showed a higher activity of Leydig cells on the treated group when compared to the control group, which was observed degenerated mitochondria due, probably, the hiperstimulation. Furthermore, there was a trend towards a 23% increase in sperm production in treated animals and 12% in serum testosterone. Therefore, the results showed that tadalafil does not interfere negatively in testicular function when used for 30 days of 25mg/Kg dose every 24 hours. Tadalafil é um inibidor de fosfodiesterases (PDE) do tipo 5 (PDE5) que foi formulado para tratamento de disfunção erétil, contudo, até o presente momento, as informações são conflitantes quanto aos efeitos colaterais destes inibidores sobre a função testicular. Para estudar os efeitos do tadalafil sobre a função testicular, foi realizado estudo in vivo, utilizando 15 camundongos Swiss Webster (Mus musculus), machos, adultos. Os animais foram divididos em grupo controle (n=8) e grupo tratado (n=7). Os animais do grupo tratado receberam 25mg/kg de tadalafil diariamente durante 30 dias, pela via intraperitoneal (IP) enquanto os animais do grupo controle receberam solução para injeção estéril pela mesma via. Ao final do período experimental, os animais foram heparinizados, anestesiados com Xilazina e Ketamina e submetidos à eutanásia por aprofundamento anestésico. Fígado, baço, rins, próstata, vesícula seminal, epidídimos e testículos foram coletados e pesados para comparação entre grupos, fragmentos de testículo foram fixados com glutaraldeído em tampão fosfato de sódio, 0,01M e pH 7,4. Os fragmentos testiculares foram processados rotineiramente para inclusão em resina plástica à base de glicol metacrilato e analisados através de Histomorfometria e Microscopia Eletrônica. A testosterona plasmática foi determinada através de teste de ELISA após punção cardíaca e obtenção de sangue total. De acordo com os resultados, o tadalafil na dosagem e período utilizados, não produziu efeitos deletérios sobre o parênquima testicular, apenas na microscopia eletrônica demonstrou-se uma maior atividade das células de Leydig no grupo tratado quando comparado ao grupo controle, onde observou-se mitocôndrias degeneradas por provável hiper estimulação. Além disso, constatou-se tendência de aumento de 23% na produção espermática nos animais tratados e 12% na testosterona sérica. Portanto, os resultados demonstraram que o tadalafil não interfere negativamente sobre na função testicular quando utilizado por 30 dias em dose única de 25mg/Kg a cada 24 horas.

Aim The aim of this study was to evaluate the association of very low and low birth weight (VLBW and LBW) with maternal periodontitis. Material and Methods Overall, 1206 women were examined at post-partum and two alternative criteria for periodontitis definition were used: (1) four or more teeth with at least one site with probing depth (PD) ≥4 mm and clinical attachment loss (CAL) ≥3 mm; and (2) at least one site with PD and CAL ≥4 mm. For each definition, two multivariate analyses were performed: (1) linear regression for birth weight; (2) ordinal logistic regression for birth weight, categorized as adequate (n = 1046), LBW (n = 145) and VLBW (n = 15). Results Linear regression showed that maternal periodontitis was associated with a decrease in mean birth weight (periodontitis definition 1: p = 0.027; periodontitis definition 2: p = 0.003). Ordinal logistic regression showed that maternal periodontitis was associated with LBW and VLBW [odds ratio (OR) = 2.0; 95% confidence interval (CI) 1.39–2.90, when considering periodontitis definition 2]; and with LBW (OR = 1.65; 95% CI 1.15–2.36, when considering periodontitis definition 1). Conclusion Maternal periodontitis was associated with a decrease in mean birth weight, as well as with LBW and VLBW.

The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity. The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1) during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.

Association studies between maternal periodontitis and an elevated risk for preeclampsia have shown conflicting results. The aims of the present case-control study were: 1) to evaluate the association between maternal periodontitis and preeclampsia before and after matching, assessing confounding and interaction; and 2) to evaluate the influence of the extent and severity of periodontal parameters, bleeding on probing (BOP), probing depth (PD), and clinical attachment loss (CAL), in association with preeclampsia.Initially, 1,206 Brazilian women were included and divided into a control group (1,042 non-preeclamptic women who gave birth to infants with adequate gestational age and birth weight) and a case group (164 preeclamptic women). Further, 125 preeclamptic women were matched according to age, chronic hypertension, and primiparity to 375 non-preeclamptic women randomly selected from the control group. Maternal periodontitis was defined as PDor =4 mm and CALor =3 mm at the same site in at least four teeth. The effect of variables of interest and confounding were assessed by univariate and multivariate analysis.After controlling for confounders, maternal periodontitis was included in the multivariate final model (odds ratio [OR] = 1.94; 95% confidence interval [CI]: 1.37 to 2.77; P0.001) and remained associated with preeclampsia after matching (OR = 1.52; 95% CI: 1.01 to 2.29; P = 0.045). The odds of preeclampsia were associated with an increase in the number of sites with BOP and PD and CALor =4 mm.Maternal periodontitis is a risk factor associated with preeclampsia, emphasizing the importance of periodontal care in prenatal programs.

Background. The results from reports analyzing the occurrence ofgingival overgrowth (GO) induced by tacrolimus are controversial. In addition, the role of pharmacological and periodontal variables on the development and severity of GO have not been well-established. Therefore, the aim of the present study was to determine the effect of potential risk variables for GO in a Brazilian population comprising renal transplant recipients medicated with tacrolimus in the absence of calcium channel blockers. Materials and Methods. Demographic, pharmacological, and periodontal data, recorded from 125 subjects selected to participate in the study, was analyzed with the use of the independent sample t test, the chi-squared statistic, or Mann-Whitney test. The effects of risk variables on GO scores were subsequently examined using multivariate regression analysis and general linear model. Results. The prevalence of clinically significant GO (≥30%) in the study population was of 7.25%. These subjects showed greater averages of plaque scores (P=0.0043) as well as papillary bleeding index (P=0.0026) when compared to subjects with GO

It has been suggested that periodontitis is associated with systemic alterations such as adverse pregnancy outcomes. However, some conflicting results have been reported. This case-control study was conducted to determine the association between maternal periodontitis and preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR).A total of 1,305 Brazilian women from multiethnic groups were enrolled and divided into four groups: control group (1,042 women who gave birth to infants with adequate gestational age and birth weight); PTB group (238 women, gestational age37 complete weeks); LBW group (235 women, birth weight2,500 g); and IUGR group (77 women who gave birth to infants with fetal growth retardation). Periodontitis was defined as the presence of at least four teeth with one or more sites with probing depthor =4 mm and clinical attachment lossor =3 mm. The effects of variables of interest, confounders, and interaction were tested through univariate and multivariate logistic regression tests.After adjusting for variables of interest, maternal periodontitis was retained in the final model for PTB (odds ratio [OR] = 1.77; 95% confidence interval [CI]: 1.12 to 2.59), LBW (OR = 1.67; 95% CI: 1.11 to 2.51), and IUGR (OR = 2.06; 95% CI: 1.07 to 4.19). When the interaction between periodontitis and previous PTB was tested, an OR of 5.94 (P0.001), 9.12 (P0.001), and 18.90 (P0.001) was observed for PTB, LBW, and IUGR, respectively.Maternal periodontitis is associated with an increased risk for PTB, LBW, and IUGR. Results emphasize the importance of periodontal care in prenatal health programs.

A periodontite tem sido associada a alterações sistêmicas, como as intercorrências gestacionais, entretanto estes achados têm apresentado resultados conflitantes. Assim, um estudo caso-controle foi realizado para verificar a associação de risco entre periodontite materna e parto pré-termo (PPT), baixo peso ao nascer (BPN) e crescimento intra-uterino restrito (CIUR). Metodologia: Durante o estudo foram avaliadas 1305 mulheres brasileiras, com faixa etária e etnia variada, que foram dividas em: a) grupo controle (1042 mulheres que deram à luz a recém-nascidos (RNs) com idade gestacional 37 semanas e peso a 2.500 Kg); b) grupo PPT (238 mulheres com idade gestacional menor que 37 semanas); c) grupo BPN (235 mulheres que deram à luz a RNs com peso < 2500g); d) grupo CIUR (77 mulheres que deram à luz a RNs com diminuição do crescimento fetal). A periodontite foi definida como a presença de 4 ou mais dentes com no mínimo 1 sítio com profundidade de sondagem 4mm e perda de inserção clínica 3mm. O efeito de variáveis de interesse, fatores de confundimento e interação foi testado por análise uni e multivariada de regressão logística. Resultados: A periodontite materna permaneceu significativa para: PPT (Razão das Chances (RC)= 1,77, p < 0,001); BPN (RC = 1,67, p < 0,001) e CIUR (RC = 2,06, p < 0,001). Quando a interação entre periodontite e número de consultas pré-natais foi testada para PPT, BPN e CIUR, observou-se RC de 0,39, 0,46 e 1,12, (p < 0,001), respectivamente. Já a interação entre periodontite e a ocorrência de PPT prévio para PPT, BPN e CIUR observou-se RC de: 5,94, 9,12 e 18,90, (p < 0,001), respectivamente. Conclusões: A periodontite materna foi associada a um risco aumentado de PPT, BPN e CIUR, ressaltando a importância da inclusão de medidas de prevenção e tratamentos periodontais nos programas de atenção à saúde das gestantes. Background: It has been suggested that periodontitis is associated with systemic alterations such as adverse pregnancy outcomes. However, some conflicting results have been reported. This case-control study was conducted to determine the association between maternal periodontitis and preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IGR). Methods: 1,305 Brazilian women, from multiethnic groups, were enrolled and divided into: a) control group 1,042 women who gave birth to infants with adequate gestational age and birth weight; b) PTB group 238 women, gestational age

Fine needle aspiration cytology (FNAC) is an important technique in the diagnosis of oral and maxillofacial conditions. The purpose of the present paper is to report a case of oral metastasis of breast carcinoma diagnosed by FNAC.A 45-year-old, black woman was referred for evaluation of symptomatic swelling in the left mandible. The medical history revealed that the patient had undergone extensive surgery to remove a lobular carcinoma. She had finished chemotherapy treatment about 5 months earlier. Due to the main diagnostic considerations of metastatic and inflammatory disease, FNAC was performed. The cytologic picture was consistent with a metastatic glandular neoplasm.FNAC is a safe, reliable, cost-effective and easy procedure and sometimes eliminates the need for open biopsy.