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. EndProducts End Products (AGEs disorders Parkinsons Parkinson s PD, , (PD) abilities crosssectional cross sectional 2 nonPD non C. C . (C) days Assessment 0.02 002 0 02 performance 0.01 001 01 SPPB (SPPB r 0.59 059 59 -0.59 0.05. 005 0.05 05 0.05) Parkinsons. s. (PD (C 0.0 00 0.5 5 -0.5 0. -0. -0 -

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. (POP) however alternative studys s 11 (1: ratio openblind open blind 4 n each each) 3month month homogeneous p 0.030 0030 0 030 POPQ Q 0.023 0023 023 followup follow up follow-up 0.001. 0001 0.001 . 001 0.001) 0.004 0004 004 (0.004 0.005. 0005 0.005 005 0.005) 0.044. 0044 0.044 044 0.044) (POP (1 0.03 003 03 0.02 002 02 000 0.00 00 (0.00 0.04 04 ( 0.0 (0.0 0. (0. (0

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. Parkinsons Parkinson s PD. PD . (CDP setting Therefore studys (BESTest 2 (PD SitToStand Sit To Stand STS, , (STS) StepQuick Quick SQT, (SQT) (SUO Master platform 0.02 002 0 02 0.01 001 01 left 003 03 0.03 respectively, respectively respectively) 0007 007 0.007 0.001, 0001 0.001 0.001) 0.01. 0.002 0002 0.020. 0020 0.020 020 0.020) posturography information (STS (SQT 0.0 00 000 0.00 0.

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. FOXOa FOXO USMT (USMT prognosis 5 , (LMS) 11 comprising leiomyomas, leiomyomas) 2 MM (MM samples IHC, IHC (IHC) FISHCISH FISH CISH FISH/CISH qRTPCR qRT PCR analyses Additionally insilico silico genes forms ULM LM (LM OS (OS patients Intriguingly EGF/HER2 EGFHER2 EGFHER EGF/HER HER EGF/HER- signaling detected HER2 HER- miRNAs miR965p miRp miR 96 5p p miR1555p, miR1555p 155 5p, miR-155-5p Conversely miRlet7c5p miRletcp let7c let c downregulated summary activity LMS) strategies (LMS 1 (IHC 9 15 miRlet letc

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. KISS kisspeptin, kisspeptin , (kisspeptin) KISSR R receptor, receptor androgen insulin Fortyeight Forty eight groups each G1nonovariectomized Gnonovariectomized G1 nonovariectomized G control G2ovariectomized Govariectomized 50 (5 µg/Kg/day µgKgday µg Kg day µg/Kg/day) G3ovariectomized 0.75 075 0 75 (0.7 mg/kg/day mgkgday mg kg mg/kg/day) G4ovariectomized 300 (30 G5ovariectomized G5 G6ovariectomized G6 surgery 12 days period anesthesia realtime real time qRTPCR. qRTPCR qRT PCR . (qRT-PCR) p 0.001, 0001 0.001 001 0.001) 5 ( 0.7 07 7 (0. 30 (3 1 (qRT-PCR 000 0.00 00 0. (0 3 0.0

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. KISS kisspeptina, kisspeptina , (kisspeptina) KISSR R receptor kisspeptina) androgênio insulina ovariectomizadas cada G1controle Gcontrole G1 controle G ovariectomizado ovariectomizado) G2ovariectomizado Govariectomizado 50 (5 µg/Kg/dia µgKgdia µg Kg dia µg/Kg/dia) G3ovariectomizado 0,75 075 0 75 (0,7 mg/kg/dia mgkgdia mg kg mg/kg/dia) G4ovariectomizado 300 (30 G5ovariectomizado G5 G6ovariectomizado G6 cirurgia oral 12 dias período anestesia quantitative realtime time reaction qRTPCR, qRTPCR qRT PCR, PCR qRT-PCR inglês. inglês . inglês) tratados p 0,001, 0001 0,001 001 0,001) avaliados (kisspeptina 5 ( 0,7 07 7 (0, 30 (3 1 000 0,00 00 0, (0 0,0

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 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. Context environment vehicle Objectives middleaged middle aged drives Design n 62 303 30 3 30. 71 7 1 7. years 102 704 70 4 70. 58 5 8 5. MiniMental Mini Mental Examination test Results men groups Conclusions Age sex multidomains multi domains 6 10

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. Context TA (TA lifestyle Objectives shortterm short term 8week week 8 (8-week (CT (UTA Paralympics Design longitudinal study Methods Thirtyfour Thirty four groups G (G1 nonathlete non athlete (G2 phase control anamnesis blood pressure electrocardiogram rate ergometer dynamometry teams Results maximal 22 106 97 97% respectively Conclusion life (G 10 9

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

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. (VTE factors ICESP (ICESP 201 2018 167 1 0.9%, 09 0.9% , 0 9 (0.9%) 0.2%, 02 0.2% (0.2%) 12 0.7%. 07 . 7 (0.7%) groups skinsparing skin sparing nipplesparing nipple 0.032. 0032 0.032 032 0.032) abdominalbased abdominal based 4.7%, 47 4.7% 4 (4.7%) 0.033. 0033 0.033 033 0.033) 0.027, 0027 0.027 027 0.027) 6 ( vs 0.001. 0001 0.001 001 0.001) (LMWH (0.2 1.2% 0048 048 0.04 0.7 27 2.7% 0.039 0039 039 respectively especially flaps, flaps) skinsparing/nipplesparing skinsparingnipplesparing sparing/nipple mastectomies 20 16 0.9 (0.9% 0.2 (0.7% 003 0.03 03 4.7 (4.7% 002 0.02 000 0.00 00 (0. 1.2 004 04 0.0 0. 2.7 sparingnipple (0.9 (0.7 4. (4.7 (0 1. 2. (4. (4