Abstract Introduction Advanced Glycation End-Products (AGEs) are a diverse group of highly reactive molecules that play a vital role in the development of neurodegenerative disorders, such as Parkinson's Disease (PD), leading to a decline in functional and cognitive capacity. The objective of this study was to assess the intake and quantification of AGEs in individuals with PD and to correlate them with their functional and cognitive abilities. Methods This was a cross-sectional study involving 20 PD patients and 20 non-PD individuals as the Control group (C). The autofluorescence reader was used to evaluate skin AGEs, while food recall was used to quantify AGEs consumed for three different days. The Montreal Cognitive Assessment, Short Physical Performance Battery, and handgrip tests were used. PD patients demonstrated greater impairment in functional capacity compared to the control group. Results Dominant Handgrip (p = 0.02) and motor performance, in the sit and stand test (p = 0.01) and Short Physical Performance Battery (SPPB) (p = 0.01) were inferior in PD patients than the control group. Although PD patients tended to consume less AGEs than the control group, AGE intake was negatively correlated with handgrip strength in individuals with PD (r = -0.59; p < 0.05). Conclusion PD patients had lower strength and functional capacity, suggesting that the effects of AGEs might be exacerbated during chronic diseases like Parkinson's.

Abstract Introduction and hypothesis Internal vaginal pessary is among the leading treatments for pelvic organ prolapse (POP); however, it has a high adverse event rate. An external pessary was recently developed as an alternative. The study's objective was to compare the efficacy of external and internal pessaries in treating POP in postmenopausal women. Methods This parallel randomized (1:1 ratio) open-blind study included 40 symptomatic women with stage 2 or 3 POP. They were randomized into two groups: group 1 (internal pessary) and group 2 (external pessary) (n = 20 in each); and evaluated at the start of and 3 months after the treatment. Statistical analysis was performed to compare the results within and between the groups before and after the 3-month treatment. Results The groups were homogeneous, except for the variables previous pregnancies (p = 0.030) and POP-Q score of apical prolapse (p = 0.023) whose values were higher in group 2. A significant improvement in quality of life was observed in both groups after 3 months of follow-up; however, internal pessaries were found to be more effective (p < 0.001). In group 1 there were differences between the initial and final POP-Q scores of anterior (0.004) and apical prolapse (p = 0.005). The complication rate associated with internal pessary use was high (p = 0.044). Conclusions The present data suggested that external pessaries have a similar effect to internal ones for the treatment of POP and improvement of the quality of life of postmenopausal women.

Abstract Introduction An accurate assessment of balance problems is critical for decreasing the risk of falling in patients with Parkinson's Disease (PD). Reliable diagnostic tools such as Computerized Dynamic Posturography (CDP) are not feasible for the clinical setting. Therefore, the present study's aim was to assess the correlation between the clinical Balance Evaluation Systems Test (BESTest) and CDP. Methods 20 male older adults with Parkinson's Disease (PD) were included in this study. Participants first executed the Sit-To-Stand (STS), Step/Quick turn (SQT), and Step Up and Over (SUO) tests on a Balance Master® force platform, followed by a clinical balance evaluation using the BESTest. Results Four outcomes of the CDP were negatively correlated with one or more BESTest domains or total BESTest score: STS sway velocity was negatively correlated with the anticipatory postural adjustment (p = 0.02) and sensory orientation (p = 0.01) domains. SQT turn time was negatively correlated with biomechanical restriction (for turns to the left, p = 0.01, and right, p = 0.03, respectively), postural response (p = 0.01, p = 0.01), dynamic balance during gait (p = 0.007, p = 0.001), and total score (p = 0.02, p = 0.01). Step over time to the right in SUP was negatively correlated with the limits of the stability domain (p = 0.002) and total BESTest score (p = 0.020). SUO impact index was negatively correlated with the anticipatory postural adjustment domain (p = 0.01). Conclusion This study shows that several BESTest domains are significantly correlated with CDP outcomes, demonstrating that the BESTest can be used as a more clinically feasible alternative for computerized posturography, without loss of information.

Abstract Objective The present study aimed to investigate FOXO3a deregulation in Uterine Smooth Muscle Tumors (USMT) and its potential association with cancer development and prognosis. Methods The authors analyzed gene and protein expression profiles of FOXO3a in 56 uterine Leiomyosarcomas (LMS), 119 leiomyomas (comprising conventional and unusual leiomyomas), and 20 Myometrium (MM) samples. The authors used techniques such as Immunohistochemistry (IHC), FISH/CISH, and qRT-PCR for the present analyses. Additionally, the authors conducted an in-silico analysis to understand the interaction network involving FOXO3a and its correlated genes. Results This investigation revealed distinct expression patterns of the FOXO3a gene and protein, including both normal and phosphorylated forms. Expression levels were notably elevated in LMS, and Unusual Leiomyomas (ULM) compared to conventional Leiomyomas (LM) and Myometrium (MM) samples. This upregulation was significantly associated with metastasis and Overall Survival (OS) in LMS patients. Intriguingly, FOXO3a deregulation did not seem to be influenced by EGF/HER-2 signaling, as there were minimal levels of EGF and VEGF expression detected, and HER-2 and EGFR were negative in the analyzed samples. In the examination of miRNAs, the authors observed upregulation of miR-96-5p and miR-155-5p, which are known negative regulators of FOXO3a, in LMS samples. Conversely, the tumor suppressor miR-let7c-5p was downregulated. Conclusions In summary, the outcomes of the present study suggest that the imbalance in FOXO3a within Uterine Smooth Muscle Tumors might arise from both protein phosphorylation and miRNA activity. FOXO3a could emerge as a promising therapeutic target for individuals with Unusual Leiomyomas and Leiomyosarcomas (ULM and LMS), offering novel directions for treatment strategies.

Abstract Background Acknowledging the relationship between postural control and muscle strength in lower limbs is important to find persons with high fall risk and to design fall prevention exercise programs. Objective To investigate the connection between knee muscle strength, semi-static postural balance, and functional mobility in irregularly active older women. Methods One hundred and ten older women aged 60 to 85 years underwent a semi-static postural balance test in a force and functional mobility measured by Timed Up & Go (TUG) with and without Cognitive Tasks (CT). Muscle strength of the knee was assessed by isokinetic dynamometry at 60°/s. Results A negative correlation between the functional mobility (TUG with and without CT) and the muscular strength of the knee was observed. Regarding semi-static balance, there was a low negative correlation with peak torque corrected for body weight of the extensors with the following variables with eyes open: Mean Velocity Dominant limb (D) (r = -0.19; p = 0.03); and anteroposterior range Non-Dominant limb (ND) (r = -0.19; p = 0.04); with eyes closed: mediolateral range ND limb (r = -0.21; p = 0.02) and Mean Velocity ND limb (r = -0.18; p = 0.05). Conclusions This study found that better functional mobility was associated with greater muscle strength in the knee in elderly women. There were weak negative correlations between knee extensor strength and some measures of semi-static postural balance, suggesting that different motor control actions are required to maintain semi-static balance and mobility. In the case of semi-static balance, a lower level of muscle response is required than in functional mobility.

Abstract Background Brazil faces notable Breast Cancer (BC) mortality despite lower incidence rates versus developed countries. Despite guidelines from medical societies, Brazilian public policy recommends biennial mammographic screening for women aged 50 to 69. This study investigates sociodemographic and clinical factors related to BC detection methods and clinical stage at diagnosis. Methods The authors conducted a cross-sectional study at a São Paulo tertiary hospital. Patients were divided into ‘symptomatic’ and ‘mammographic’ detection groups. Bivariate analyses by detection method and clinical stage compared groups' profiles in terms of sociodemographic and clinical characteristics. Poisson regression analyses assessed sociodemographic and molecular subtypes´ influence on “mammographic detection” prevalence and “advanced-stage BC”, reporting prevalence ratios and 95 % Confidence Intervals. Results The authors studied 1,536 BC patients admitted from January 2016 to December 2017. The “mammographic detection” group had a higher proportion of patients aged 50‒69 years (62.9 % vs. 44.1 %), white race (63.3 % vs. 51.6 %), Catholic religion (58.2 % vs. 51.1 %), and Luminal A subtype (25.2 % vs. 13.2 %) compared to the “symptomatic detection” group. Patients with early-stage disease were more likely to have higher education levels (8.1 % vs. 5.5 %) and be married (39.8 % vs. 46.6 %) compared to those with advanced-stage. Molecular subtypes were significantly associated with the detection method and stage. The prevalence of advanced-stage disease in "mammographic" (n=313) and "symptomatic" (n=1191) groups was 18.5 % and 55 %, respectively . Mammographic detection significantly reduced advanced-stage BC prevalence (PR = 0.40, 95 % CI 0.31‒0.51). Conclusion Mammographic detection reduces advanced-stage breast cancer prevalence in Brazil, emphasizing the importance of regular screenings, especially among at-risk sociodemographic groups. Enhancing mammographic screening accessibility, lowering the starting age to 40, and extending coverage to include annual mammograms can significantly lower breast cancer mortality in Brazil, benefiting public health and patient outcomes.

Resumo Objetivo Avaliar os efeitos do estrogênio, raloxifeno e genisteína na expressão de KISS1 (kisspeptina), KISS1R (receptor da kisspeptina), AR (receptor de androgênio) e INSR (receptor de insulina) nos ossos de ratas ovariectomizadas. Métodos Quarenta e oito ratas adultas foram divididas aleatoriamente em 6 grupos, contendo 8 animais cada: G1–controle não ovariectomizado); G2–ovariectomizado e tratado com estrogênios conjugados equinos (50 µg/Kg/dia); G3–ovariectomizado e tratado com raloxifeno (0,75 mg/kg/dia); G4–ovariectomizado que recebeu extrato de soja com genisteína (300 mg/kg/dia); G5–ovariectomizado que recebeu estrogênio e genisteína; e G6–ovariectomizado que recebeu estrogênio e raloxifeno. Após 3 meses da cirurgia, os animais castrados receberam os fármacos diariamente por via oral, durante 120 dias. Todos os animais foram sacrificados após esse período, por aprofundamento da anestesia. A tíbia esquerda foi removida para extração de RNA total e análise da expressão gênica de KISS1, KISS1R, AR e INSR, por reação de cadeia de polimerase quantitativa em tempo real (quantitative real-time polymerase chain reaction, qRT-PCR, em inglês). Resultados KISS1 não foi detectado em nenhum dos grupos tratados. KISS1R, INSR e AR mostraram maior expressão no grupo G3 (p < 0,001), enquanto menores níveis de transcritos para esses genes foram observados em G4 e G5. Os animais de G2 apresentaram hipoexpressão dos genes avaliados. Conclusão Os resultados indicam que o raloxifeno, isolado ou combinado com estrogênio, foi capaz de induzir a expressão de genes associados à recuperação da homeostase do tecido ósseo em ratas ovariectomizadas.

Abstract Objective To evaluate the effects of estrogen, raloxifene and genistein on the expression of KISS1 (kisspeptin), KISS1R (kisspeptin receptor), AR (androgen receptor) and INSR (insulin receptor) in the bones of ovariectomized rats. Methods Forty-eight adult rats were randomly divided into 6 groups, containing 8 animals each: G1–nonovariectomized control; G2–ovariectomized and treated with conjugated equine estrogens (50 µg/Kg/day); G3–ovariectomized and treated with raloxifene (0.75 mg/kg/day); G4–ovariectomized animal that received soy extract with genistein (300 mg/kg/day); G5–ovariectomized animal that received estrogen and genistein; and G6–ovariectomized animal that received estrogen and raloxifene. Three months after surgery, the castrated animals received the drugs orally daily for 120 days. All animals were sacrificed after this period, by deepening the anesthesia. The left tibia was removed for total RNA extraction and analysis of gene expression of KISS1, KISS1R, AR and INSR, by quantitative real-time polymerase chain reaction (qRT-PCR). Results KISS1 was not detected in any of the treated groups. KISS1R, INSR and AR showed higher expression in the G3 group (p < 0.001), while lower levels of transcripts for these genes were observed in G4 and G5. G2 animals showed hypoexpression of the evaluated genes. Conclusion The results indicate that raloxifene, alone or combined with estrogen, was able to induce the expression of genes associated with the recovery of bone tissue homeostasis in ovariectomized rats.

SUMMARY OBJECTIVE: The aim of this study was to evaluate the effectiveness of cognitive behavioral therapy in the treatment of vasomotor, sexual dysfunction, and recurrent depression in postmenopausal women. METHODS: This prospective, open study evaluated 112 postmenopausal women with vasomotor symptoms. Sexual dysfunction has cultural, social, biological, and emotional issues and divided into two groups: G1, without depression (n=65) and G2, with recurrent depression (n=47). The subjects underwent 12 sessions of in-person cognitive behavioral therapy and 12 sessions of home-based activity over a period of 6 months. They were evaluated at 3 months following the completion of therapy. Depression, memory, and attention-related functions, as well as climactic symptoms, were assessed using a questionnaire. RESULTS: In the depression questionnaire, the G1 group had a lower initial score than the G2 group (p<0.01). Following 6 months of therapy, both groups had similar improved scores. In the depression questionnaire, the women in group G1 had higher baseline values. In the assessment of vasomotor symptoms, the values in both groups were similar and showed an improvement in vasomotor symptoms after 24 weeks of treatment, but these effects disappeared after the follow-up of 48 weeks in the G2 group. Both groups improved the sexual dysfunction after 24 weeks. CONCLUSION: Cognitive behavioral therapy may be effective in reducing vasomotor symptoms and ameliorate the sexual dysfunction and recurrent depression in postmenopausal women after 24 weeks of treatment.

Abstract Context: Vehicle driving depends on the integration of motor, visual, and cognitive skills to respond appropriately to different situations that occur in traffic. Objectives: To analyze a model of performance predictor for braking time in the driving simulator, using a battery of tests divided by gender. Methods: Selected were 100 male drivers with a mean age of 72.6 ± 5.7 years. Sociode-mographic variables, braking time in the driving simulator, and motor, visual, and cognitive skills were evaluated. Results: Comparing genders, men were older than women (p = 0.002) and had longer driving times (p = 0.001). Men had more strength in hand grip (p ≤ 0.001). In the linear regression analysis, the model explained 68 % of the braking time in men and 50.8 % in women. In the stepwise multiple linear regression analysis, the variable that remained in the model was the strength of the right plantar flexors, which explained 13 % of the braking time in women and men, and the cognitive variables explained 38.9 %. Conclusion: Sociodemographic, motor, visual, and cognitive variables, explained a substantial portion of the variability in braking time for both older women and men, the specific variables driving this performance differed between the sexes. For older women, factors such as muscle strength emerged as critical determinants of braking ability, highlighting the importance of physical health in maintaining driving skills. On the other hand, cognitive conditions emerged as the primary predictor of braking performance in older men, underscoring the role of mental acuity and decision-making processes in safe driving.

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. OBJECTIVE <9 >9 METHODS 201 inclusion 3 31 reviewed malecaused caused Also 18 earlyan latean . RESULTS 9 p<0.04. p004 p p<0.04 0 04 (p<0.04) 585 58 5 58.5 434 43 4 43.4% respectively 163 63 1.6 95% 95 (95 104 1.0 2.55. 255 2.55 55 2.55) CONCLUSION (<9 phenomenon < > 20 p00 p<0.0 (p<0.04 58. 43.4 16 6 1. (9 10 25 2.5 (< p0 p<0. (p<0.0 43. ( 2. p<0 (p<0. p< (p<0 (p< (p

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. FOXOa FOXO a tumorigenesis mechanisms posttranscriptional post transcriptional initiation Here (LA TripleNegative Triple Negative (TN timePCR time PCR method evaluated miR965p miRp miR 96 5p miR1825p, miR1825p 182 5p, described de scribed FOXO3A FOXOA tissue 7.82 782 7 82 (7.8 times 0.005 0005 0 005 612 6 12 6.1 respectively 9.42 942 9 42 (9.4 0.0001 00001 0001 851 8 51 8.5 tissues FR 4 immunostaining 0.001, 0.001 , 001 0.001) behavior 18 7.8 78 (7. 0.00 000 00 61 1 6. 9.4 94 (9. 0.000 0000 85 5 8. 7. (7 0.0 9. (9 ( 0.