Abstract Objective: Sjögren’s Syndrome (SS) is a chronic inflammatory autoimmune exocrinopathy, and although, the role of metabolism in the autoimmune responses has been discussed in diseases such as lupus erythematosus, rheumatoid arthritis, psoriasis and scleroderma. There is a lack of information regarding the metabolic implications of SS. Considering that the disease affects primarily salivary glands; the aim of this study is to evaluate the metabolic changes in the salivary glands’ microenvironment using a targeted metabolomics approach. Methods: The saliva from 10 patients diagnosed with SS by the American-European consensus and 10 healthy volunteers was analyzed in an Ultra-high Performance Liquid Chromatograph Coupled Mass Spectrometry (UPLCMS). Results: The results showed an increased concentration in SS of metabolites involved in oxidative stress such as lactate, alanine and malate, and amino acids involved in the growth and proliferation of T-cells, such as arginine, leucine valine and isoleucine. Conclusions: These results revealed that is possible to differentiate the metabolic profile of SS and healthy individuals using a small amount of saliva, which in its turn may reflect the cellular changes observed in the microenvironments of damaged salivary glands from these patients. Objective Sjögrens Sjögren s (SS exocrinopathy although erythematosus arthritis scleroderma approach Methods 1 AmericanEuropean American European Ultrahigh Ultra high UPLCMS. UPLCMS . (UPLCMS) Results lactate malate Tcells, Tcells T cells, cells T-cells arginine isoleucine Conclusions (UPLCMS

Abstract Background The presence of Extracapsular Extension (ECE) in the Sentinel Lymph Node Biopsy (SLNB) is still a doubt in the literature. Some studies suggest that the presence of ECE may be related to a greater number of positive axillary lymph nodes which could impact Disease Free Survival (DFS) and Overall Survival (OS). This study searches for the clinical significance of the ECE. Methods Retrospective cohort comparing the presence or absence of ECE in T1-2 invasive breast cancer with positive SLNB. All cases treated surgically at the Cancer Institute of the State of São Paulo (ICESP) between 2009 and 2013 were analyzed. All patients with axillary disease in SLNB underwent AD. Outcomes Identify the association between the presence and length of ECE and additional axillary positive lymph nodes, OS and DFS between both groups. Results 128 patients with positive SLNB were included, and 65 had ECE. The mean metastasis size of 0.62 (SD = 0.59) mm at SLNB was related to the presence of ECE (p < 0.008). The presence of ECE was related to a higher mean of positive sentinel lymph nodes, 3.9 (± 4.8) vs. 2.0 (± 2.1), p = 0.001. The median length of follow-up was 115 months. The OS and DFS rates had no differences between the groups. Conclusion The presence of ECE was associated with additional positive axillary lymph nodes in this study. Therefore, the OS and DFS were similar in both groups after 10 years of follow-up. It is necessary for additional studies to define the importance of AD when SLNB with ECE. (ECE (SLNB literature (DFS OS. . (OS) T12 T T1 2 T1- ICESP (ICESP 200 201 analyzed 12 included 6 062 0 62 0.6 SD 0.59 059 59 0.008. 0008 0.008 008 0.008) 39 3 9 3. ± ( 4.8 48 4 8 vs 20 2. 2.1, 21 2.1 , 1 2.1) 0001 001 0.001 followup follow up 11 months Therefore followup. up. (OS 06 0. 0.5 05 5 000 0.00 00 4. 0.0

RESUMO OBJETIVO Avaliar os efeitos ovarianos da melatonina (Mel) em ratas com síndrome dos ovários policísticos (SOP) antes e após a indução do estro-permanente. MÉTODOS Trinta e duas ratas com ciclos estrais regulares foram igualmente divididas em quatro grupos: 1) GCtrl - fase de estro. 2) GSOP - fase de estro-permanente. 3) GMel1 – tratadas por 60 dias com Mel (0,4 mg/kg) durante a indução do estro-permanente e 4) GMel2 – ratas com SOP e tratadas com Mel. Após eutanásia dos animais, os ovários foram processados para inclusão em parafina. Cortes foram corados com H.E ou submetidos à imuno-histoquímica para detecção de Ki-67 e caspase-3 clivada (Casp-3). RESULTADOS O GSOP mostrou ausência de corpos lúteos e vários cistos ovarianos, além de inúmeras células intersticiais. A presença de corpos lúteos e o aumento significativo dos folículos primários e antrais foram observados nos grupos tratados com Mel, os quais também mostraram diminuição no número de cistos ovarianos e na área ocupada pelas células intersticiais. Esses resultados foram mais evidentes no GMel1 do que no GMel2. A porcentagem de células Ki-67 positivas foi significativamente maior no GMel1 e no GMel2, sendo mais evidente no GMel2, em comparação ao GSOP. Por outro lado, a porcentagem de células positivas à Casp-3 foi menor nas células da granulosa do GMel1 e maior nas células intersticiais do GMel2, em comparação ao GSOP. CONCLUSÃO A administração de melatonina previne o estado de estro-permanente em ratas com SOP. Esse efeito é mais eficiente quando a melatonina é administrada após indução do estado de estro-permanente.

SUMMARY OBJECTIVE To evaluate the ovarian effects of melatonin (Mel) in a rat model of polycystic-ovary-syndrome (PCOS) before and after permanent estrus induction. METHODS Thirty-two adult-female rats with regular estrous cycle were equally divided into four groups: 1) GCtrl – at estrous phase. 2) GPCOS - at permanent-estrous phase. 3) GMel1 – treated for 60 days with Mel (0.4 mg/Kg) during permanent estrus induction and 4) GMel2 – rats with PCOS and treated for 60 days with Mel. After that, the animals were euthanized, and the ovaries were removed and processed for paraffin embedding. Sections were stained with H.E. for histomorphometry or subjected to immunohistochemistry for Ki-67 and cleaved caspase-3 (Casp-3) detections. RESULTS The GPCOS showed lack of corpus luteum and several ovarian cysts, as well as interstitial-like cells. The presence of corpus luteum and a significant increase in primary and antral follicles were observed in Mel-treated groups, which also showed a decrease in the number of ovarian cysts and in the area occupied by interstitial-like cells. These results were more evident in GMel1. The percentage of Ki-67-positive cells was significantly higher in the Mel-treated groups, mainly in the GMel2, as compared to GPCOS. On the other hand, the percentage of Casp-3-positive cells was significantly lower in granulosa cells of GMel1, whereas it was significantly higher in the interstitial-like cells of GMel2, in comparison to GPCOS. CONCLUSION Melatonin administration prevents the permanent estrus state in the PCOS rat model. This effect is more efficient when melatonin is administered before permanent estrus induction.

OBJECTIVES: Despite the number of surgical advances and innovations in techniques over time, radical vulvectomy frequently results in substantial loss of tissue that cannot be primarily closed without tension, the mobilization of surrounding tissues or even the rotation of myocutaneous flaps. The aim of this study was to evaluate the feasibility of leaving the surgical vulvar open wound for secondary healing in situations where primary closure of the vulvar wound is not possible. METHODS: This case-control pilot study analyzed 16 women with a diagnosis of squamous cell carcinoma of the vulva who first underwent inguinofemoral lymphadenectomy, 6-week sessions of chemotherapy and 25 daily sessions of radiotherapy. Afterward, excision of the vulvar lesion with free margins was performed between January 2011 and July 2017. Twelve patients underwent primary closure of the wound (control), and in 4 patients, the surgical wound was left open for secondary healing by means of a hydrofiber (case). The inclusion criteria were a) FIGO-2009 stage II up to IIIC; b) squamous cell carcinoma; and c) no evidence of pelvic or extrapelvic disease or pelvic nodal involvement. The exclusion criteria were extrapelvic disease or pelvic nodal involvement, another primary cancer, or a poor clinical condition. ClinicalTrials.gov: NCT02067052. RESULTS: The mean age of the patients at the time of the intervention was 62.1. The distribution of the stages was as follows: II, n=6 (37 %); IIIA, n=1 (6%), IIIB, n=1 (6%) and IIIC, n=8 (51%). The mean operative time was 45 minutes. The hospital stay duration was 2 days. Full vulvar healing occurred after an average of 30 days in the control group and after an average of 50 days in the case group. CONCLUSION: A secondary healing strategy may be an option for the treatment of vulvar cancer in situations of non-extensive surgical wounds when primary closure of the wound is not possible.

Resumo Objetivo Avaliar os aspectos de saúde das mulheres brasileiras após os 65 anos de idade. Métodos O estudo foi retrospectivo, e incluiu 1.001mulheres brasileiras atendidas no ambulatório de ginecologia geriátrica de nossa instituição. Foi feita uma análise transversal de mulheres com idade acima de 65 anos, incluindo dados demográficos, sintomas clínicos (sintomas vasomotores), morbidades associadas, bem como alterações no exame físico e queixas em relação à atividade sexual. Utilizamos o teste qui-quadrado para avaliar os dados. Resultados A idade das pacientes na primeira visita clínica variou de 65 a 98 anos, com média etária de 68,56 ± 4,47 anos. A média etária de entrada na menopausa foi de 48,76 ± 5,07 anos. Os sintomas clínicos mais frequentes relatados durante o período analisado foram os sintomas vasomotores (n = 188), seguidos de artropatia, astenia e vagina seca. Asmorbidades associadasmais frequentes após os65anos foram hipertensão arterial sistêmica, distúrbios gastrintestinais, diabete melito e depressão, entre outras. A avaliação do índice de massa corporal (IMC) mostrou redução deste parâmetro antropométrico com o progredir da idade. No momento da visita, 78 pacientes relataram ter relações sexuais. A maioria das mulheres que relatou ter relações sexuais (89,75%, n = 70) estava entre 65 e 69 anos, 8,97% (n = 7) tinham entre 70 e 74 anos, e apenas 1,28% (n = 1) eram mais velhas do que 75 anos de idade. Conclusões Nossos achados sugerem que os sintomas vasomotores podem persistir após os 65 anos. Houve uma diminuição significativa na relação sexual com o aumento da idade. Os distúrbios cardiovasculares em nosso estudo são preocupações de saúde nestas mulheres.

Abstract Purpose The aim of this study was to evaluate the health aspects of Brazilian women older than 65 years of age. Design This was a retrospective study that included 1,001 Brazilian women cared for in the gynecological geriatric outpatient office of our institution. We report a crosssectional analysis of female adults aged over 65 years, including data on demographics, clinical symptoms such as vasomotor symptoms, associated morbidities, physical examination and sexual intercourse. We used the chi-squared test to assess the data. Results The age of the patients on their first clinic visit ranged from65 to 98 years, with a mean age of 68.56 ± 4.47 years; their mean age at the time of natural menopause was 48.76 ± 5.07 years. The most frequent clinical symptoms reported during the analyzed period were hot flashes (n = 188), followed by arthropathy, asthenia, and dry vagina. The most frequent associated morbidities after 65 years of age were systemic arterial hypertension, gastrointestinal disturbance, diabetes mellitus, and depression, among others. The assessment of the bodymass index (BMI) found decreases inBMIwith increased age. At the time of the visit, 78 patients reported sexual intercourse. The majority of women reporting sexual intercourse (89.75%, n = 70) were between 65 and 69 years of age, 8.97% (n = 7) were between 70 and 74 years of age, and only 1.28% (n = 1) of those were aged older than 75 years. Conclusions Our findings suggested that vasomotor symptoms can persist after 65 years of age. There was a significant decrease in sexual intercourse with increased age. The cardiovascular disturbances in our study are health concerns in these women.

OBJECTIVE: To evaluate the influence of estrogen therapy and estrogen-progestin therapy on homocysteine and C-reactive protein levels in postmenopausal women. METHODS: In total, 99 postmenopausal women were included in this double-blind, randomized clinical trial and divided into three groups: Group A used estrogen therapy alone (2.0 mg of 17β-estradiol), Group B received estrogen-progestin therapy (2.0 mg of 17 β-estradiol +1.0 mg of norethisterone acetate) and Group C received a placebo (control). The length of treatment was six months. Serum measurements of homocysteine and C-reactive protein were carried out prior to the onset of treatment and following six months of therapy. RESULTS: After six months of treatment, there was a 20.7% reduction in homocysteine levels and a 100.5% increase in C-reactive protein levels in the group of women who used estrogen therapy. With respect to the estrogen-progestin group, there was a 12.2% decrease in homocysteine levels and a 93.5% increase in C-reactive protein levels. CONCLUSION: Our data suggested that hormone therapy (unopposed estrogen or estrogen associated with progestin) may have a positive influence on decreasing cardiovascular risk due to a significant reduction in homocysteine levels.

Objetivo: avaliar a expressão imunoistoquímica de marcadores de proliferação, apoptose e enzimas esteroidogênicas nos ovários de ratas com síndrome dos ovários policísticos (SOP). Métodos: vinte ratas foram divididas em dois grupos: controle (GCtrl), na fase de estro, e com síndrome dos ovários policísticos (GSOP). Os animais do GCtrl permaneceram com período de luz das 7 às 19 horas, e os do GSOP com iluminação contínua, durante 60 dias. Posteriormente, os animais foram anestesiados, os ovários removidos e fixados em formol a 10% para inclusão em parafina. Cortes histológicos foram corados pelo H.E. e outros submetidos a métodos imunoistoquímicos para detecção de Ki-67, caspase 3 clivada, CYP11A1, CYP17A1 e CYP19A1. Os resultados foram submetidos ao teste t de Student (p < 0,05). Resultados: a morfologia mostrou evidências da origem das células intersticiais a partir das células da teca interna dos cistos ovarianos em degeneração no GSOP. A imunoexpressão do Ki-67 mostrou-se aumentada nas células da granulosa no GCtrl e na teca interna do GSOP, enquanto a caspase 3 clivada se mostrou aumentada nas células da granulosa dos cistos ovarianos do GSOP e na teca interna do GCtrl. A imunorreatividade da CYP11A1 nas células da teca interna, bem como da granulosa e intersticiais, mostrou-se semelhante entre os dois grupos. As CYP17A1 e CYP19A1 apresentaram-se aumentadas nas células da granulosa e intersticiais no grupo SOP. Conclusão: os resultados indicam que as células intersticiais são oriundas da teca interna e que ocorrem alterações enzimáticas nas células da teca interna e intersticiais do ovário de ratas com SOP, responsáveis pelos altos níveis de androgênios e de estradiol.

Objective: to evaluate the immunohistochemical expression of proliferative, apoptotic and steroidogenic enzyme markers in the ovaries of rats with polycystic ovary syndrome (PCOS). Methods: twenty rats were divided into two groups: GCtrl - estrous phase, and PCOS - with polycystic ovaries. The GCtrl animals were subjected to a lighting period from 7 am to 7 pm, while the animals with PCOS group remained with continuous lighting for 60 days. Subsequently, the animals were anesthetized, the ovaries were removed and fixed in 10% formaldehyde, prior to paraffin embedding. Sections were stained using H.E. or subjected to immunohistochemical methods for the detection of Ki-67, cleaved caspase-3, CYP11A1, CYP17A1 and CYP19A1. The results were analyzed using Student's t-test (p < 0,05). Results: morphological results showed evidence of interstitial cells originating from the inner theca cells of degenerating ovarian cysts in PCOS. Immunoexpression of Ki-67 was higher in the granulosa cells in GCtrl, and the theca interna cells in PCOS, while cleaved caspase-3 was higher in granulosa cells of ovarian cysts from PCOS and in the theca interna cells of GCtrl. Immunoreactivity of CYP11A1 in the theca interna, granulosa and interstitial cells was similar between the two groups, while CYP17A1 and CYP19A1 were higher in the granulosa and interstitial cells in the PCOS group. Conclusion: the results indicate that the interstitial cells are derived from the theca interna and that enzymatic changes occur in the theca interna and interstitial cells in ovaries of rats with PCOS, responsible for the high levels of androgens and estradiol.

O endométrio humano é submetido a uma complexa série de mudanças proliferativas e secretórias em cada ciclo menstrual e exibe somente pequeno período de receptividade, conhecido como "janela de implantação", necessário para a nidação do blastocisto no útero. O processo da implantação ocorre de forma sequencial, levando ao estabelecimento da gravidez. Alterações morfofuncionais durante este período podem impedir ou dificultar a implantação. Por este motivo, o estudo do endométrio nesta fase é importante para o aprimoramento de terapias que possam interferir nos mecanismos envolvidos na interção materno-embrionária. Várias doenças ginecológicas, incluindo a síndrome dos ovários policísticos (SOP), estão associadas à diminuição da fecundidade e da receptividade uterinas. Apesar de recentes avanços nas técnicas de reprodução assistida, permitindo a seleção de embriões de alta qualidade, a taxa de implantação continua baixa e não tem aumentado suficientemente nas últimas décadas. O presente artigo tem como objetivo revisar os aspectos endometriais da "janela de implantação" em mulheres com a síndrome dos ovários policísticos, focando especialmente as moléculas de adesão. Para tanto, nos valemos da análise de 105 artigos publicados em revistas indexadas no PUBMED nos últimos 50 anos (até maio de 2011). Como conclusão, a receptividade endometrial parece ser o maior fator limitante no estabelecimento da gestação em grande número de doenças ginecológicas, incluindo a SOP, e o tratamento para melhorar as taxas de implantação possivelmente será nessa direção.

The human endometrium undergoes to a complex series of prolifertive and secretory changes in each menstrual cycle and displays only a short period of receptivity, known as the "window of implantation", necessary for the implantation of the blastocyst in the uterus. The implantation process occurs in a sequential manner, leading to the establishment of pregnancy. Morphofunctional changes during this period may prevent or hinder the implantation. For this reason, the study of the endometrium at this stage is important for the improvement of therapies that may interfere with the mechanisms involved in maternal-embryonic interaction. Several gynecological disorders, including polycystic ovary syndrome (PCOS), are associated with decreased fertility and uterine receptivity. In spite of recent advances in assisted reproduction techniques, allowing the selection of high quality embryos, the implantation rate remains low and has not increased enough in recent decades. This article aims at reviewing the endometrial aspects of the "window of implantation" in women with polycystic ovary syndrome, focusing mainly on adhesion molecules. For that purpose, we analyzed 105 articles published in journals indexed in PubMed in the last 50 years (up to May 2011). In conclusion, the endometrial receptivity seems to be the major limiting factor for the establishment of pregnancy in a large number of gynecological diseases, including PCOS, and treatment to improve implantation rates is likely to be taken towards this direction.

RESUMO Objetivo: O objetivo deste estudo foi avaliar o comportamento sexual em mulheres com síndrome dos ovários policísticos e a relação de comportamento sexual e parâmetros clínicos relacionados a essa síndrome (obesidade, hirsutismo e irregularidade menstrual). Métodos: Um estudo transversal foi realizado com 48 mulheres com síndrome dos ovários policísticos. A avaliação foi baseada nas queixas referidas pelas pacientes com ênfase na satisfação sexual, existência ou não de parceiro, fases do ciclo da resposta sexual (desejo, excitação orgasmo e resolução), frequência sexual, prática de masturbação, avaliação de práticas sexuais menos habituais, grau de intimidade e qualidade de comunicação no envolvimento com o parceiro. As variáveis do comportamento sexual (satisfação sexual, masturbação, fantasia sexual, frequências de desejo, de excitação e de orgasmo) foram comparadas com três parâmetros clínicos: ciclo menstrual, hirsutismo e índice de massa corporal (IMC). Resultados: A iniciação sexual, as formas de expressão da sexualidade, a intimidade comunicativa com o parceiro e a satisfação sexual não foram influenciadas pela síndrome. Em relação à associação dos parâmetros clínicos da síndrome dos ovários policísticos com o comportamento sexual, correlação estatisticamente significativa foi encontrada com o ciclo menstrual. Conclusão: A ausência de menstruação exerceu impacto sobre o interesse sexual não vinculado às atividades com o parceiro, aumentando a frequência de masturbação.

ABSTRACT Objective: The objective of this study was to evaluate the sexual behavior of women with polycystic ovary syndrome and the relationship between sexual behavior and the clinical parameters related to this syndrome (obesity, hirsutism and menstrual irregularities). Methods: A cross-sectional study was carried out involving 48 women with polycystic ovary syndrome. The evaluation was based on the complaints reported by the women with particular emphasis on sexual satisfaction, the presence of a sexual partner, phases of the sexual response cycle (desire, arousal, orgasm and resolution phases), sexual frequency, practice of masturbation, evaluation of less usual sexual habits, degree of intimacy and the quality of communication in the women's involvement with their sexual partner. The variables of sexual behavior (sexual satisfaction, masturbation, sexual fantasies, frequency of desire, arousal and orgasm) were compared with three clinical parameters: menstrual cycle, hirsutism and body mass index (BMI). Results: The sexual initiation, ways of expressing sexuality, communication and intimacy with partner and sexual satisfaction were not influenced by the clinical aspects of the syndrome. With respect to association of polycystic ovary syndrome clinical parameters with sexual behavior, a statistically significant correlation was found with the menstrual cycle. Conclusion: The absence of menstruation affected sexual interest in activities not involving the partner, thus increasing the frequency of masturbation.