SUMMARY OBJECTIVE: This study sought to evaluate the influence of time (early <90 days and late >90 days) and endometrial injury on pregnancy success. METHODS: This is a retrospective study in which all infertile women who underwent at least one in vitro fertilization cycle at Clinica Gera between 2010 and 2015 were considered for inclusion. We included patients with a normal ovarian reserve and regular menses at intervals of up to 30 days. A total of 315 patient files were reviewed, and the study group was composed of patients who faced fertility issues and had male-caused infertility or idiopathic infertility. Also, women with male or unknown cause of infertility who have performed endometrial biopsy and have undergone embryo transfer up to 180 days after this procedure between 2010 and 2015 were included. The patients were divided into two groups according to the interval between biopsy and embryo transfer: group 1 (early—an interval of <90 days) and group 2 (late—an interval of >90 days and up to 180 days). RESULTS: The results were superior for the group with an interval of less than 90 days relative to the group with an interval of more than 90 days (p<0.04). The pregnancy rates for group 1 and group 2 were 58.5% and 43.4%, respectively. The odds ratio for pregnancy success was 1.63 (95% confidence interval: 1.04 to 2.55). CONCLUSION: The early transfer of embryos (<90 days) may produce better results with a high rate of pregnancy. Further studies are necessary to identify the mechanism involved in this phenomenon.

Abstract Introduction The CA1 region of the hippocampus has an important role in learning and memory. It has been shown that estrogen deficiency may reduce the synaptic density in the region and that hormone replacement therapy may attenuate the reduction. Objectives This study aimed to evaluate the effects of estrogen and raloxifene on the synaptic density profile in the CA1 region of the hippocampus in ovariectomized rats. Methods Sixty ovariectomized three-month-old virgin rats were randomized into six groups (n = 10). Treatments started either three days (early treatment) or sixty days (late treatment) after ovariectomy. The groups received propylene glycol vehicle (0.5 mL/animal/day), equine conjugated estrogens (50 μg/animal/day), or raloxifene (3 mg/kg/day) either early or late after ovariectomy. The drugs were administered orally by gavage for 30 days. At the end of the treatments, the animals were anesthetized and transcardially perfused with ether and saline solution. The brains were removed and prepared for analysis under transmission electron microscopy and later fixed. Results Results showed a significant increase in the synaptic density profile of the hippocampal CA1 region in both the early estrogen (0.534 ± 0.026 µ/m2) and the early raloxifene (0.437 ± 0.012 µ/m2) treatment groups compared to the early or late vehicle-treated control groups (0.338 ± 0.038 µ/m2 and 0.277 ± 0.015 µ/m2 respectively). Conclusions The present data suggest that the raloxifene effect may be lower than that of estrogen, even early or late treatment, on synaptic density in the hippocampus.

Abstract PCOS is an endocrine disorder characterized by chronic anovulation, hyperandrogenism, and polycystic ovaries. Its etiology is uncertain. It is debated whether BPA would be a component of the environmental factor in the etiology of PCOS. Contamination by BPA can occur from food packaging (exposure during the diet) and through skin absorption and/or inhalation. It can be transferred to the fetus via the placenta or to the infant via breast milk, and it can be found in follicular fluid, fetal serum, and amniotic fluid. The phenolic structure of BPA allows it to interact with Estrogen Receptors (ERs) through genomic signaling, in which BPA binds to nuclear ERα or Erβ, or through nongenomic signaling by binding to membrane ERs, prompting a rapid and intense response. With daily and constant exposure, BPA's tendency to bioaccumulate and its ability to activate nongenomic signaling pathways can alter women's metabolic and reproductive function, leading to hyperandrogenism, insulin resistance, obesity, atherogenic dyslipidemia, chronic inflammatory state, and anovulation and favoring PCOS. The harmful changes caused by BPA can be passed on to future generations without the need for additional exposure because of epigenetic modifications. Not only high BPA levels can produce harmful effects, but at low levels, BPA may be harmful when exposure occurs during the most vulnerable periods, such as the fetal and neonatal periods, as well as during the prepubertal age causing an early accumulation of BPA in the body. Learning how BPA participates in the pathogenesis of PCOS poses a challenge and further studies should be conducted.

Abstract Context: Many studies show the importance of evaluating the adaptation time of subjects in a virtual driving environment, looking forwards to a response as closest as a possible real vehicle. Objectives: This study aimed to identify and analyze the adaptation to the driving simulator in older adults and middle-aged adults with and without a distraction, and a secondary aim was to identify predictors of safe performance for older adults’ drives. Design: Male and female middle-aged adults (n = 62, age = 30.3 ± 7.1 years) and older adults (n = 102, age = 70.4 ± 5.8 years) were evaluated for braking time performance in a driving simulator; cognition performance assessment included the Mini-Mental State Examination; motor evaluation included ankle flexor muscle strength with the isokinetic dynamometer and handgrip strength; the postural balance was evaluated with Timed Up and Go test, with and without a cognitive distraction task. Results: Older adults (men and women) and middle-aged adult women require more time to adapt to the driving simulator. The distractor increases the adaptation time for all groups. The main predictors of braking time for older women are age, muscle strength, and postural balance associated with distraction, and for older men, muscle strength. Conclusions: Age, sex, and distractor interfere in the adaptation of the virtual task of driving in a simulator. The evaluation model developed with multi-domains demonstrated the ability to predict which skills are related to braking time with and without the presence of the distractor.

Abstract FOXO3a dysregulation is frequently implicated in tumorigenesis, and its inhibition can occur by several molecular mechanisms. Among these, post-transcriptional suppression by miRNAs has been associated with various cancers initiation. Here, we assessed the expression profiles of the most relevant miRNAs for breast tumorigenesis, using Luminal A (LA) and Triple-Negative (TN) breast cancer from Brazilian patients, by the quantitative real time-PCR method. Their potential prognostic role for the patients was also evaluated. We identified the miRNAs miR-96-5p and miR-182-5p, de-scribed as negative regulators of FOXO3A, with differential expression both in LA and TN tumors when compared to normal tissue. The miR-96-5p and miR-182-5p miRNAs were upregulated in LA (7.82 times, p < 0.005; 6.12 times, p < 0.005, respectively) and TN breast cancer samples (9.42 times, p < 0.0001; 8.51 times, p < 0.0001) compared to normal tissues. The samples with higher miR-96-5p and miR-182-5p expression (FR ≥ 4) were submitted for FOXO3a immunostaining. Reduced protein detection was observed in all of the tumors compared to normal tissues. The most prominent miRNA expression and FOXO3a protein suppression were observed in TN samples (p < 0.001), indicating the relevant role of these molecules in this tumor biology and clinical behavior. Our results corroborate the literature regarding to the relevance of FOXO3a in the breast cancer, and they open new perspectives for alternative target therapy options for Brazilian patients expressing both FOXO3a and its regulatory miRNAs.

Abstract Context: Transtibial Amputation (TA) predisposes to a sedentary lifestyle. Objectives: To evaluate the efficiency of a short-term (8-week) Concurrent Training (CT) program in Unilateral Transtibial Amputees (UTA) and to compare it with the physical condition of a group of Paralympic athletes in preparation for the Rio de Janeiro Paralympics. Design: This was a longitudinal, prospective and controlled trial study. Methods: Thirty-four male subjects with UTA and using prostheses for six months or more were selected for this study. They were divided into two groups: Group 1 (G1) – 17 non-athlete and untrained UTA and Group 2 (G2) – 17 paralympic athletes with active UTA in the training phase. G1 was evaluated before and after eight weeks of CT and G2 made a single evaluation for control. All were submitted to anamnesis, clinical evaluation (blood pressure, electrocardiogram, and heart rate) and cardiopulmonary exercise testing on a lower limb cycle ergometer, and isokinetic knee dynamometry. The CT of G1 included resistance exercise and aerobic interval training on a stationary bicycle and G2 followed the training of the Paralympic teams. Results: Patients were retested by the same methods after CT. The two most important central dependent variables (maximal oxygen uptake and muscular strength) increased by 22% and knee extensor and flexor strength by 106% and 97%, respectively. Conclusion: After eight weeks of CT, there was an improvement in general functional condition, muscle strength, and cardiorespiratory performance improving protection against chronic diseases and quality of life.

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.

Abstract Background Venous Thromboembolism (VTE) is an important cause of morbidity in cancer patients. Breast cancer patients undergoing surgical treatment are at an increased risk of VTE. The aim of this study was to determine the frequency of VTE in patients who underwent surgery for the treatment of breast cancer and to identify the related risk factors. Methods A historical cohort of patients at the São Paulo State Cancer Institute (ICESP) underwent surgery for breast cancer. The inclusion criteria covered patients with invasive breast cancer or ductal carcinoma in situ who had breast surgery anytime from January 2016 to December 2018. Results Of the 1672 patients included in the study, 15 had a confirmed diagnosis of VTE (0.9%), and 3 of these had deep vein thrombosis (0.2%), and 12, had pulmonary thromboembolism (0.7%). Clinical and tumoral characteristics did not differ between the groups. The incidence of VTE was higher in patients who had undergone skin-sparing mastectomy or nipple-sparing mastectomy (p = 0.032). Immediate reconstruction, particularly with abdominal-based flaps (4.7%), increased VTE events (p = 0.033). Median surgical time was higher in patients with VTE episodes (p = 0.027), and total hospital length of stay increased in days (6 days vs. 2 days, p = 0.001). Neoadjuvant chemotherapy and postoperative prophylaxis with Low Molecular Weight Heparin (LMWH) were associated with lower VTE rates (0.2% vs. 1.2%, p = 0.048 and 0.7% vs. 2.7%, p = 0.039; respectively) in these patients. Conclusions The incidence of VTE events in breast cancer patients who underwent surgery was 0.9%. Immediate reconstruction (especially with abdominal-based flaps), skin-sparing/nipple-sparing mastectomies, and longer surgeries were associated with increased risk. The LMWH postoperative prophylaxis reduced this risk.

Resumo Objetivo Sabe-se que a transferência de embrião único (SET) é a melhor escolha para reduzir as gestações múltiplas e riscos associados. A prática da criopreservação de todos os embriões para transferência posterior tem sido cada vez mais utilizada para fertilização in vitro (FIV), em especial quando há risco de síndrome de hiperestimulação ovariana ou realização de teste genético pré-implantacional. Entretanto, sua utilização disseminada ainda é controversa. O objetivo deste estudo foi avaliar a eficácia de duas SET sequenciais em comparação com uma transferência de embrião dupla (DET) em ciclos de FIV onde todos os embriões foram criopreservados. Métodos Neste estudo retrospectivo foram revisados 5.156 ciclos de FIV realizados entre 2011 e 2019, e 506 ciclos usando oócitos próprios e criopreservação de todos os embriões com transferências eletivas subsequentes de embriões descongelados, foram selecionados para este estudo. Ciclos com transferência eletiva de embrião único (eSET, n = 209) compuseram nosso grupo de estudo e como grupo de controle incluímos os ciclos com transferência eletiva de dois embriões (eDET, n = 291). No grupo eSET, 57 casais que falharam na 1ª tentativa de eSET tiveram uma 2ª eFET e a taxa de gravidez em curso cumulativa foi estimada para o grupo eSET e comparada com o grupo eDET. Resultados Após a 1ª eFET, as taxas de gravidez em curso foram semelhantes entre os grupos (eSET: 35,4% versus eDET: 38,5%; p = 0,497), mas a taxa de gravidez em curso cumulativa estimada após a 2ª eFET no grupo eSET (eSET + SET) foi significativamente maior (48,8%) do que no grupo eDET (p <0,001). Além disso, as taxas de gestação múltipla foram expressivamente inferiores no grupo eSET + SET (2,7%) quando comparado ao grupo eDET (30,4%; p < 0,001). Conclusão Nosso estudo mostrou que a associação das estratégias de congelamento de todos os embriões com até duas eSETs sequenciais resultou em maiores taxas de sucesso do que uma DET com embriões descongelados, além de reduzir drasticamente a ocorrência de gestações múltiplas.

Abstract Objective It is known that the single embryo transfer (SET) is the best choice to reduce multiples and associated risks. The practice of cryopreserving all embryos for posterior transfer has been increasingly performed for in vitro fertilization (IVF) patients at the risk of ovarian hyperstimulation syndrome or preimplantation genetic testing for aneuploidy. However, its widespread practice is still controverse. The aim of this study was to evaluate how effective is the transfer of two sequential SET procedures compared with a double embryo transfer (DET) in freeze-only cycles. Methods This retrospective study reviewed 5,156 IVF cycles performed between 2011 and 2019, and 506 cycles using own oocytes and freeze-only policy with subsequent elective frozen-thawed embryo transfers (eFET) were selected for this study. Cycles having elective SET (eSET, n = 209) comprised our study group and as control group we included cycles performed with elective DET (eDET, n = 291). In the eSET group, 57 couples who had failed in the 1st eSET had a 2nd eFET, and the estimated cumulative ongoing pregnancy rate was calculated and compared with eDET. Results After the 1st eFET, the ongoing pregnancy rates were similar between groups (eSET: 35.4% versus eDET: 38.5%; p =0.497), but the estimated cumulative ongoing pregnancy rate after a 2nd eFET in the eSET group (eSET + SET) was significantly higher (48.8%) than in the eDET group (p < 0.001). Additionally, the eSET +SET group had a 2.7% rate of multiple gestations, which is significantly lower than the eDET group, with a 30.4% rate (p < 0.001). Conclusion Our study showed the association of freeze-only strategy with until up to two consecutive frozen-thawed eSETs resulted in higher success rates than a frozenthawed DET, while drastically reducing the rate of multiple pregnancies.