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Clinics, Volume: 77, Publicado: 2022
  • COVID-19 pandemic repercussions on undergraduate teaching in obstetrics and gynecology Editorial

    Ribeiro, Lívia Sousa; Francisco, Rossana Pulcineli Vieira; Cabar, Fábio Roberto
  • A new era for the international representativeness of CLINICS Journal Editorials

    Moreira, Luiz Felipe P.; Soares Jr., José Maria
  • The right to vaccination and the individual duty in collective health during a pandemic Editorial

    Franco, Juliana Bertoldi; Gutierrez, Pilar Lecussan; Cabar, Fábio Roberto; Lin, Chin An
  • SARS-CoV-2 vaccines: Potential refinements through induction of mucosal and trained immunity Editorials

    Portilho, Amanda Izeli; Lima, Gabrielle Gimenes; DeGaspari, Elizabeth
  • Sex differences in Parkinson’s Disease: An emerging health question Editorials

    Ferreira, Luiz Philipe de Souza; Silva, Rafael André da; Costa, Matheus Marques Mesquita da; Roda, Vinicius Moraes de Paiva; Vizcaino, Santiago; Janisset, Nilma R.L.L.; Vieira, Renata Ramos; Sanches, José Marcos; Soares Junior, José Maria; Simões, Manuel de Jesus
  • Long non-coding RNA DLGAP1 antisense RNA 1 accelerates glioma progression via the microRNA-628-5p/DEAD-box helicase 59 pathway Original Articles

    Hu, Ke-qi; Ao, Xiang-sheng

    Resumo em Inglês:

    Abstract Objectives Abnormal expression of long non-coding RNAs (lncRNAs) plays a prominent role in glioma progression. However, the biological function and mechanism of lncRNA DLGAP1 antisense RNA 1 (DLGAP1-AS1) in gliomas are still unknown. Methods The authors assessed DLGAP1-AS1 and miR-628-5p expression in glioma tissues and cell lines using quantitative real-time polymerase chain reaction (qRT-PCR) and evaluated their effects on glioma cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) using the cell counting kit-8 (CCK-8) assay, 5-Ethynyl-2′-deoxyuridine (EdU) assay, Transwell assay, and western blot, respectively. The expression of DEAD-box helicase 59 (DDX59) was quantified using western blotting, and a dual-luciferase reporter gene assay was performed to detect the interaction between DLGAP1-AS1 and miR-628-5p. Results The authors observed increased DLGAP1-AS1 expression in glioma tissues and cell lines with higher WHO grades and shorter survival time. DLGAP1-AS1 promoted the proliferation, migration, invasion, and EMT of glioma cells, while miR-628-5p counteracted these effects. The authors identified DLGAP1-AS1 as a molecular sponge of miR-628-5p in glioma cells as the biological functions of DLGAP1-AS1 are partially mediated via miR-628-5p. In addition, DLGAP1-AS1 upregulated DDX59 expression by inhibiting miR-628-5p expression. Conclusion The DLGAP1-AS1/miR-628-5p/DDX59 axis regulates glioma progression.
  • Readmission of late preterm and term neonates in the neonatal period Original Articles

    Kardum, Darjan; Serdarušić, Ivana; Biljan, Borna; Šantić, Krešimir; Živković, Vinko

    Resumo em Inglês:

    Abstract Objective To determine the incidence of hospital readmissions in late preterm and term neonates, the most common reasons for readmission, and analyze the risk factors for readmission in the neonatal period. Methods Newborn infants admitted to a well-baby nursery ≥ 36 weeks gestation were included in this retrospective cohort study. Data for all infants born in a 3-year period and readmitted in the first 28 days of life were analyzed. Indication for readmission was one diagnosed during initial workup in the pediatric emergency room visit before readmission. Results The final cohort consisted of 5408 infants. The readmission rate was 4.0% (219/5408). Leading readmission causes were respiratory tract infection (29.58%), jaundice (13.70%), and urinary tract infection (9.59%). The mean ± SD age of readmitted infants was 13.3 ± 7.1 days. The mean ± SD treatment duration of treatment was 5.5 ± 3.0 days. In the multivariate regression analysis, infants that were during the initial hospitalization transferred to special care/NICU had a lower chance of readmission during the neonatal period (p = 0.04, OR = 0.23, 95% CI 0.06-0.93). Infants with mothers aged from 19-24 years had a higher risk of readmission (p = 0.005, OR = 1.62, 95% CI 1.16-2.26). Conclusions Finding that infants that were during the initial hospitalization transferred to special care or a NICU setting were less likely to require hospitalization in the neonatal period is an interesting one. Further research into how different approach in these settings reduce the risk of readmission is necessary. Highlights In infants gestational age ≥ 36 weeks the readmission rate is 4.0%. Most common causes are respiratory infections, jaundice, and feeding problems. Initial care in special care or NICU setting showed reduced readmission rates.
  • Effects of ganglioside GM1 and erythropoietin on spinal cord injury in mice: Functional and immunohistochemical assessments Original Articles

    Torelli, Alessandro Gonzalez; Cristante, Alexandre Fogaça; Barros-Filho, Tarcísio Eloy Pessoa de; Santos, Gustavo Bispo dos; Morena, Beatriz Cintra; Correia, Felipe Fernandes; Paschon, Vera

    Resumo em Inglês:

    ABSTRACT Objectives: To evaluate the functional and immunohistochemical effects of ganglioside GM1 and erythropoietin following experimental spinal cord injury. Methods: Thirty-two male BALB/c mice were subjected to experimental spinal cord injury using the NYU Impactor device and were randomly divided into the following groups: GM1 group, receiving standard ganglioside GM1 (30 mg/kg); erythropoietin group, receiving erythropoietin (1000 IU/kg); combination group, receiving both drugs; and control group, receiving saline (0.9%). Animals were evaluated according to the Basso Mouse Scale (BMS) and Hindlimb Mouse Function Score (MFS). After euthanasia, the immunohistochemistry of the medullary tissue of mice was analyzed. All animals received intraperitoneal treatment. Results: The GM1 group had higher BMS and MFS scores at the end of the experiment when compared to all other groups. The combination group had higher BMS and MFS scores than the erythropoietin and control groups. The erythropoietin group had higher BMS and MFS scores than the control group. Immunohistochemical tissue analysis showed a significant difference among groups. There was a significant increase in myelinated axons and in the myelinated axon length in the erythropoietin group when compared to the other intervention groups (p < 0.01). Conclusion: Erythropoietin and GM1 have therapeutic effects on axonal regeneration in mice subjected to experimental spinal cord injury, and administration of GM1 alone had the highest scores on the BMS and MFS scales.
  • Influence of invertor and evertor muscle fatigue on functional jump tests and postural control: A prospective cross-sectional study Original Articles

    Castillo, Gabriela Borin; Brech, Guilherme Carlos; Luna, Nátalia Mariana Silva; Tarallo, Fernanda Botta; Soares-Junior, Jose Maria; Baracat, Edmund Chada; Alonso, Angelica Castilho; Greve, Júlia Maria D’Andréa

    Resumo em Inglês:

    ABSTRACT Objective: Fatigue of the ankle’s stabilizing muscles may influence the performance of functional activities and postural control. The purpose of this study was to evaluate the performance of healthy young adults using functional jump tests and static posturography control under pre- and post-fatigue conditions of the ankle invertor and evertor muscles. Methods: Thirty physically active healthy male and female (15 male and 15 female) volunteers (24.3 years) were enrolled in this prospective cross-sectional study. Participants performed tests on one day under a non-fatigued state of invertor and evertor muscles and on the second day in a fatigued state. Tests included static posturography on a force platform in a bipedal stance with eyes open and closed and in one-legged support with eyes open and functional jump tests (figure-of-8, side hop, 6-m crossover hop, and square hop). Fatigue of the ankle invertor and evertor muscles was induced using isokinetic dynamometry with 30 repetitions at 120°/s. Results: Participants had an average age of 24.3 years (SD ± 2.08), the height of 1.73 m (SD ± 0.08), and a weight of 68.63 kg (SD ± 10.29). The average Body Mass Index (BMI) was 22.88 (SD ± 2.46). A decrease in performance was observed in functional activities and postural control under all conditions after the induction of muscle fatigue, except for the speed at a bipedal stance with eyes open. Conclusions: Functional jump tests are low cost and useful for clinical practice and evaluation of the effects of muscle fatigue and could be used in clinical practice.
  • Risk of osteoporotic fracture in women using the FRAX tool with and without bone mineral density score in patients followed at a tertiary outpatient clinic ‒ An observational study Original Articles

    Favarato, Maria Helena Sampaio; Almeida, Maria Flora de; Lichtenstein, Arnaldo; Martins, Milton de Arruda; Ferreira Junior, Mario

    Resumo em Inglês:

    ABSTRACT Objectives: Fragility fractures increase morbidity and mortality. Adding assessment of clinical risk factors independently or as a previous step to Bone Densitometry (BD) should provide better accuracy in fracture risk prediction. FRAX tool might be used to stratify patients in order to rationalize the need for BD and risk classification. The primary objective of this study is to describe and perform comparisons between the estimated risk of fractures in 10 years using the FRAX calculator based on clinical factors with and without BD results for women aged 40 or more with clinical diseases monitored in tertiary care service in internal medicine. Methods: Cross-sectional. Women over 40 years with BD in the previous year. After medical chart review, identification of risk factors and risk estimations using FRAX-BRAZIL with (FRAX BDI) and without (FRAX BDNI) the inclusion of T-score. Results: 239 women. Age 65 ± 10.35 years. BMI 29.68 ± 6.27kg/m2. Risk factors: 32(13.4%) previous fractures; 23 (9.6%) current smoking; 78 (32.6%) corticosteroids use; 44 (18.4%) rheumatoid arthritis; 38 (15.9%) secondary causes; FRAX scores were higher when BD was not included. Spearman correlation coefficients between FRAX BDNI and FRAX BDI for major fractures r = 0.793 (95% CI 0.7388‒0.836). For hip fractures r = 0.6922 (95% CI 0.6174‒0.75446) Conclusion: Using FRAX to estimate 10-year fracture risk without BD data might be a reliable tool for screening, even for patients with a high prevalence of risk factors, improving accessibility and equity in health systems. The present study’s data suggest an overestimation of fracture risk with FRAX BDNI, suggesting that it is safe to be widely used as a screening tool.
  • Increasing rate of anti-SARS-CoV-2 antibodies between the first and second waves of COVID-19 in Sao Paulo, Brazil: A cross-sectional blood donors-based study Original Articles

    Vale, Nayara Moya Rios do; Latini, Flavia Roche Moreira; Arnoni, Carine Prisco; Parreira, Rafael Martins; Girão, Manoel João Batista Castelo; Cortez, Afonso Jose Pereira; Bonetti, Tatiana Carvalho de Souza

    Resumo em Inglês:

    ABSTRACT Background: SARS-CoV-2 infections rapidly spread along with Brazilian territory with heterogeneous transmission and mortality rates, mostly depending on region and period. Investigation of SARS-CoV-2 antibodies is an important tool to understand virus circulation. Given that blood donors are a representative casuistic of a healthy population, the authors evaluated the seroprevalence of IgG and IgM COVID-19 antibodies in 2,806 blood donors from a blood bank located in São Paulo, Brazil. Methods: Aiming to evaluate viral behavior over time, the authors selected samples from blood donors who donated in June and October 2020, and February 2021. To determine whether socio-demographic features affected the seroprevalence, the authors analyzed samples from three different regions from São Paulo (capital, metropolitan and countryside regions) and evaluated predictors as gender, age, educational level, race, and use of public transportation. Results: As expected, the authors observed that seroprevalence increased over time. Seroprevalence was greater in São Paulo city compared to metropolitan and countryside regions, being smallest in the countryside. Characteristics associated with a lower percentage of antibodies were age above 50 years, higher educational level, self-declared Caucasian, and use of individual transportation. Conclusion: In conclusion, blood donors' samples proved to accurately reflect virus circulation in the healthy population.
  • Clinical value of preferred endoscopic ultrasound-guided antegrade surgery in the treatment of extrahepatic bile duct malignant obstruction Original Articles

    Zhao, Xuan; Shi, Lihong; Wang, Jinchen; Guo, Siming; Zhu, Sumin

    Resumo em Inglês:

    ABSTRACT Objectives: To explore the clinical value of preferred ultrasound endoscopic guided biliary drainage in patients with extrahepatic biliary obstruction with intrahepatic biliary ectasis. Methods: A total of 58 patients with malignant obstruction and intrahepatic bile duct expansion, including 32 males, 26 females and median age 65 (58-81) were selected. A prospective randomized controlled study was randomized into EUS-AG and ERCP-BD, with 28 patients in EUS-AG and 30 in ERCP-BD. The efficacy of the two treatments, operation success rate, operation time, the incidence of complications, hospitalization days, cost, unimpeded stent duration, and survival time were compared. Results: 1) The surgical success rate in group EUS-AG was 100%, and in group, ERCP-BD was 96.67%. There was no statistical difference in surgical success rate in the two groups (p>0.05). 2) Average operating time in EUS-AG was (23.69±11.57) min, and in ERCP-BD was (36.75±17.69) min. The difference between the two groups has statistical significance (p<0.05). 3) The clinical symptoms of successful patients were significantly relieved. Compared with the preoperative procedure, the differences in group levels had statistical significance (p<0.05); TBIL, ALP, WBC and CRP levels, no statistical significance difference in groups (p>0.05). Conclusion: EUS-AG operation has short time, low incidence of complications, safe, effective, and can be used as the preferred treatment plan for patients with extrahepatic biliary duct malignant obstruction associated with intrahepatic biliary duct expansion; EUS-AG operation has more unique clinical advantages for patients with altered gastrointestinal anatomy or upper gastrointestinal obstruction.
  • MicroRNA-128b mediates lipopolysaccharide-induced apoptosis via reactive oxygen species in human pulmonary microvascular endothelial cells Original Articles

    Long, Guangwen; Yang, Xiulin; Ji, Chunling; Dong, Yukang

    Resumo em Inglês:

    ABSTRACT Objectives: This study aimed to explore the effects of miR-128b in the regulation of Lipopolysaccharide (LPS) induced apoptosis. Methods: Human Pulmonary Microvascular Endothelial Cells (HPMECs) were transfected with an miR-128b inhibitor and stimulated with LPS for 24 h. FCM was performed to detect apoptosis and Reactive Oxygen Species (ROS) production. In addition, miRNA and caspase-3 expression levels were determined using real-time quantitative polymerase chain reaction and western blotting. Results: LPS significantly induced apoptosis and ROS production and upregulated miR-128b and caspase-3 expressions in HPMECs. However, LPS-induced effects were suppressed when an miR-128b inhibitor was used. Preincu-bation with NAC decreased the LPS-induced apoptosis of HPMECs. Conclusions: These effects were mediated by miR-128b via the caspase-3 pathway.
  • Lacticaseibacillus rhamnosus modulates the inflammatory response and the subsequent lung damage in a murine model of acute lung inflammation Original Articles

    Olimpio, Fabiana; Silva, Jose Roberto Mateus da; Vieira, Rodolfo P.; Oliveira, Carlos R.; Aimbire, Flavio

    Resumo em Inglês:

    ABSTRACT Objective: The present study investigated the anti-inflammatory effect of the probiotic Lacticaseibacillus rhamnosus (Lr) on lung inflammation induced by Lipopolysaccharide (LPS) of Escherichia coli in C57BL/6 mice. Methods: C57BL/6 mice were divided into four groups: control, LPS, Lr (1 day) + LPS, and Lr (14 days) + LPS. Total and differential cells from Bronchoalveolar Lavage Fluid (BALF) were counted in a Neubauer 40X chamber, and pro-and anti-inflammatory cytokines (IL-1β, IL-6, CXCL-1, TNF-α, TGF-β, and IL-10) were measured by ELISA assay. The analysis of whole leukocytes in blood was performed using the automated system Sysmex 800i. Morphometry of pulmonary tissue evaluated alveolar hemorrhage, alveolar collapse, and inflammatory cells. Pulmonary vascular permeability was assessed by Evans blue dye extravasation, and bronchoconstriction was evaluated in a tissue bath station. The transcription factor NF-kB was evaluated by ELISA, and its gene expression and TLR-2, TLR-4, MMP-9, MMP-12, and TIMP by PCR. Results: The probiotic Lr had a protective effect against the inflammatory responses induced by LPS. Lr significantly reduced pro-inflammatory cells in the airways, lung parenchyma, and blood leukocytes. Furthermore, Lr reduced the production of pro-inflammatory cytokines and chemokines in BALF and the expression of TLRs, MMPs, and NF-kB in lung tissue and maintained the expression of TIMP in treated animals promoting a protective effect on lung tissue. Conclusions: The results of the study indicate that pre-treatment with the probiotic Lr may be a promising way to mitigate lung inflammation in endotoxemia.
  • Chronic inflammatory diseases, subclinical atherosclerosis, and cardiovascular diseases: Design, objectives, and baseline characteristics of a prospective case-cohort study ‒ ELSA-Brasil Original Articles

    Bensenor, Isabela M.; Goulart, Alessandra C.; Pereira, Alexandre C.; Brunoni, André R.; Alencar, Airlane; Santos, Raul D.; Bittencourt, Márcio S.; Telles, Rosa W.; Machado, Luciana Andrade Carneiro; Barreto, Sandhi Maria; de Almeida-Pititto, Bianca; Janovsky, Carolina Porto Silva; Sgarbi, José Augusto; Tebar, William R.; Meneghini, Vandrize; Barbosa Junior, Fernando; Ribeiro, Ana Cristina de Medeiros; Pasoto, Sandra Gofinet; Pereira, Rosa Maria R.; Bonfá, Eloísa; Sipahi, Aytan M.; Santos, Itamar de S.; Lotufo, Paulo A.

    Resumo em Inglês:

    Abstract Objectives This analysis describes the protocol of a study with a case-cohort to design to prospectively evaluate the incidence of subclinical atherosclerosis and Cardiovascular Disease (CVD) in Chronic Inflammatory Disease (CID) participants compared to non-diseased ones. Methods A high-risk group for CID was defined based on data collected in all visits on self-reported medical diagnosis, use of medicines, and levels of high-sensitivity C-Reactive Protein >10 mg/L. The comparison group is the Aleatory Cohort Sample (ACS): a group with 10% of participants selected at baseline who represent the entire cohort. In both groups, specific biomarkers for DIC, markers of subclinical atherosclerosis, and CVD morbimortality will be tested using weighted Cox. Results The high-risk group (n = 2,949; aged 53.6 ± 9.2; 65.5% women) and the ACS (n=1543; 52.2±8.8; 54.1% women) were identified. Beyond being older and mostly women, participants in the high-risk group present low average income (29.1% vs. 24.8%, p < 0.0001), higher BMI (Kg/m2) (28.1 vs. 26.9, p < 0.0001), higher waist circumference (cm) (93.3 vs. 91, p < 0.0001), higher frequencies of hypertension (40.2% vs. 34.5%, p < 0.0001), diabetes (20.7% vs. 17%, p = 0.003) depression (5.8% vs. 3.9%, p = 0.007) and higher levels of GlycA a new inflammatory marker (p < 0.0001) compared to the ACS. Conclusions The high-risk group selected mostly women, older, lower-income/education, higher BMI, waist circumference, and of hypertension, diabetes, depression, and higher levels of GlycA when compared to the ACS. The strategy chosen to define the high-risk group seems adequate given that multiple sociodemographic and clinical characteristics are compatible with CID.
  • Circ_0075825 promotes gastric cancer progression via adsorbing miR-432-5p to modulate SOX9 Original Articles

    Li, He; Zhou, Xiaohua; Yu, Zhuangming; Tian, Youjing

    Resumo em Inglês:

    Abstract Methods Circ_0075825 expression in adjacent tissues and GC tissues was evaluated by bioinformatics method and quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). How circ_0075825 regulated GC cell growth, migration, invasion, and apoptosis were investigated by cell counting kit-8 assay, transwell assay and flow cytometry. The targeted interplays among circ_0075825, and miR-432-5p and Sex-Determining Region Y-related high-mobility group box 9 (SOX9) were explored by bioinformatics analysis and luciferase reporter gene assay. The regulatory effects of circ_0075825 and miR-432-5p on SOX9 protein expression were probed by western blot. Results Circ_0075825 expression was raised in GC tissues and cell lines. Circ_0075825 overexpression promoted the proliferative, migrative and invasive abilities of GC cells, while inhibiting apoptosis, while depletion of circ_0075825 suppressed the malignant biological behaviors of GC cells. SOX9 was identified as one of the direct target genes of miR-432-5p, and circ_0075825 repressed the expression of miR-432-5p, to induce the expression of SOX9. Furthermore, miR-432-5p overexpression counteracted the promoting effect of circ_0075825 on the malignancy of GC cells. Conclusion Circ_0075825 promotes GC progression via sponging miR-432-5p to regulate SOX9 expression level, and it may be a novel therapeutic target for treating GC.
  • IRF4 suppresses osteogenic differentiation of BM-MSCs by transcriptionally activating miR-636/DOCK9 axis Original Articles

    Zhang, Xuepu; Zhang, Yue; Yang, Limin; Wu, Yuexin; Ma, Xiaohu; Tong, Gang; Ban, Zhaoliang; Zhao, Haosen

    Resumo em Inglês:

    Abstract Objectives Osteoblasts are derived from Bone Marrow-derived Mesenchymal Stem Cells (BM-MSCs), which play an indispensable role in bone formation. In this study, the authors aim to investigate the role of IRF4 in the osteogenic differentiation of BM-MSCs and its potential molecular mechanism. Methods The authors used lentivirus infection to overexpress IRF4 in BM-MSCs. The expression of IRF4 and osteogenesis-related genes were detected by qRT-PCR and western blot analysis. The osteogenic differentiation of BM-MSCs was evaluated by Alkaline Phosphatase (ALP) activity, Alizarin red staining, and Alkaline Phosphatase (ALP) staining. Chromatin Immunoprecipitation (ChIP), Dual-Luciferase reporter assay and RNA Immunoprecipitation Assay were applied to confirm the regulatory mechanism between IRF4, miR-636 and DOCK9. Results The authors found IRF4 was down-regulated during the osteogenic differentiation of BM-MSCs, and IRF4 overexpression could decrease the osteogenic differentiation of BM-MSCs by specifically promoting the reduction of Alkaline Phosphatase (ALP) activity and down-regulating osteogenic indicators, including OCN, OPN, Runx2 and CollA1. Mechanistically, IRF4 activated microRNA-636 (miR-636) expression via binding to its promoter region, and Dedicator of Cytokinesis 9 (DOCK9) was identified as the target of miR-636 in BM-MSCs. Moreover, the damage in the capacity of osteogenic differentiation of BM-MSCs induced by IRF4 overexpression could be rescued by miR-636 inhibition. Conclusions In summary, this paper proposed that IRF4/miR-636/DOCK9 may be considered as targets for the treatment of osteoporosis (OP).
  • Incidental thyroid carcinoma: Correlation between FNAB cytology and pathological examination in 1093 cases Original Articles

    Rodrigues, Mariana Gonçalves; da Silva, Luiz Fernando Ferraz; Araujo-Filho, Vergilius José Furtado de; Mosca, Letícia de Moraes; Araujo-Neto, Vergilius José Furtado de; Kowalski, Luiz Paulo; Carneiro, Paulo Campos

    Resumo em Inglês:

    Abstract Objective To investigate Incidental Thyroid Carcinoma (ITC) by comparing the results of Fine Needle Aspiration Biopsy (FNAB) cytology and the postoperative pathological findings. Methods Data of 1479 patients who underwent total thyroidectomy were retrieved. Three hundred eighty-six patients were excluded due to insufficient data. Each surgical specimen studied received two histopathological diagnoses: the local diagnosis ‒ for the same area in which the FNAB was performed; and the final diagnosis, which includes a study of the entire surgical specimen. Results A thousand and ninety-three patients were investigated. FNAB result was malignant in 187 patients, benign in 204, suspicious or indeterminate in 668 cases, and inconclusive in 34 cases. The prevalence of ITC was 15.1%. Most of the ITC in this series was less than 0.5 cm. The incidence of ITC was higher in Bethesda III (17.5% ITC) and IV (19% ITC) than in Bethesda II cases (1.5% false negatives and 9% ITC). Conclusion Although the incidence of false-negative results in Bethesda II nodules is only 1.5%, 9% of these patients had ITC in the thyroid parenchyma outside the nodule that underwent preoperative FNAB. The incidence of ITC in the same scenario was even higher in Bethesda III (17.5%) and Bethesda IV cases (19%). Ultrasonography-guided FNAB is an excellent method for the assessment of thyroid nodules. However, biopsy sites should be carefully selected. Despite the high incidence of incidentalomas, total thyroidectomy should not always be the treatment of choice due to its rare but potentially serious complications. The findings of the present study can assist future clinical decisions towards active surveillance strategies for the management of papillary thyroid carcinoma.
  • Clinical features of hereditary angioedema and warning signs (H4AE) for its identification Original Articles

    Giavina-Bianchi, Pedro; Aun, Marcelo Vivolo; Garcia, Juliana Fóes Bianchini; Gomes, Laís Souza; Ribeiro, Ana Júlia; Takejima, Priscila; Agondi, Rosana Câmara; Kalil, Jorge; Motta, Antonio Abilio

    Resumo em Inglês:

    Abstract Objectives The study describes a case series of hereditary angioedema with C1 Inhibitor Deficiency (C1INH-HAE) in order to corroborate six clinical warning signs “HAAAAE (H4AE)” to enable early identification of this disease. Methods The authors analyzed the C1INH-HAE cohort to analyze the clinical aspects of the present study's patients and corroborate the six clinical warning signs of the Hereditary Angioedema Brazilian Guidelines. Data regarding demographics, the onset of disease, time to diagnosis, frequency of attacks per year, organs involved, triggers, crisis duration and their outcomes, and disease treatment were collected. Then the authors developed an acronym, H4AE, to help healthcare professionals remember the warning signs. Results The authors included 98 patients in the study, with a mean age of 38.1 years, 67.3% being female, and 75.3% with a family history of HAE. HAE diagnosis was delayed, on average, 13.7 years after its initial manifestation. Exploratory laparotomy was reported by 26.9%, and orotracheal intubation by 21.3% of the present study's patients; 61.3% and 30.3% of them were admitted at least once in the hospital and in the intensive care unit, respectively. The authors constructed an acronym “H4AE” with the six warning signs of HAE: Hereditary, recurrent Angioedema, Abdominal pain, Absence of urticaria, Absence of response to antihistamines, Estrogen association. Conclusion C1INH-HAE is still underdiagnosed and associated with high morbidity. The study showed clinical features of this disease, corroborating the warning signs, which may be useful in raising awareness and improving the diagnosis of C1INH-HAE. The authors suggest the acronym “H4AE” to remind the warning signs.
  • microRNA-181a-5p impedes the proliferation, migration, and invasion of retinoblastoma cells by targeting the NRAS proto-oncogene Original Articles

    Ouyang, Ming; Liu, Guiqin; Xiong, Cheng; Rao, Jing

    Resumo em Inglês:

    Abstract Objectives Accumulating research have reported that microRNAs (miRNAs) play important roles in Retinoblastoma (RB). Nonetheless, the function and underlying mechanism of miR-181a-5p in RB remain ambiguous. Methods The relative expression levels of miR-181a-5p and NRAS mRNA were detected by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). RB cell proliferation was measured using the Cell Counting Kit-8 (CCK-8) and 5′-Bromo-2′-deoxyuridine (BrdU) assays. Transwell assays and flow cytometry were performed to detect the migration, invasion, and apoptosis of RB cells. The interaction between miR-181a-5p and NRAS was explored using luciferase experiments, western blotting, and qRT-PCR. Results miR-181a-5p expression was found to be decreased in RB tissues and cell lines, and its expression was correlated with unfavorable pathological features of the patients. In vitro experiments revealed that miR-181a-5p reduced RB cell proliferation, migration, and invasion while enhancing apoptosis. Further research confirmed that NRAS is a direct target of miR-181a-5p. miR-181a-5p inhibited NRAS expression at both the mRNA and protein levels. Co-transfection of pcDNA-NRAS or NRAS small interfering RNA (siRNA) reversed the effects of miR-181a-5p mimics or miR-181a-5p inhibitors on RB cells. Conclusion miR-181a-5p was significantly downregulated during the development of RB, and it suppressed the malignant behaviors of RB cells by targeting NRAS.
  • Magnetic resonance imaging and previous cesarean section in placenta accrete spectrum disorder: Predictor model Original Articles

    Polizio, Rodrigo Pamplona; Yamauchi, Fernando Ide; Mendes, Renata Franco Pimentel; Peres, Stela Verzinhasse; Kondo, Mario Macoto; Francisco, Rossana Pulcineli Vieira

    Resumo em Inglês:

    Abstract Objective To evaluate objective criteria of Magnetic Resonance Imaging (MRI) of Placenta Accreta Spectrum disorder (PAS) analyzing interobserver agreement and to derive a model including imaging and clinical variables to predict PAS. Methods A retrospective review including patients submitted to MRI with suspicious findings of PAS on ultrasound. Exclusion criteria were lack of pathology or surgical information and missing or poor-quality MRI. Two radiologists analyzed six MRI features, and significant clinical data were also recorded. PAS confirmed on pathology or during intraoperative findings were considered positive for the primary outcome. Variables were tested through logistic regression models. Results Final study included 96 patients with a mean age of 33 years and 73.0% of previous C-sections. All MRI features were significantly associated with PAS for both readers. After logistic regression fit, including MRI signs with a moderate or higher interobserver agreement, intraplacental T2 dark band was the most significant radiologic criteria, and ROC analysis resulted in an AUC = 0.782. After including the most relevant clinical data (previous C-section) to the model, the ROC analysis improved to an AUC = 0.893. Conclusion Simplified objective criteria on MRI, including intraplacental T2 dark band associated with clinical information of previous C-sections, had the highest accuracy and was used for a predictive model of PAS.
  • Plasma lathosterol measures rates of cholesterol synthesis and efficiency of dietary phytosterols in reducing the plasma cholesterol concentration Original Articles

    Nunes, Valéria Sutti; Ilha, Angela de Oliveira Godoy; Ferreira, Guilherme da Silva; Bombo, Renata de Paula Assis; Afonso, Milessa Silva; Lavrador, Maria Silvia Ferrari; Machado, Roberta Marcondes; Nakandakare, Edna Regina; Quintão, Eder Carlos Rocha; Lottenberg, Ana Maria

    Resumo em Inglês:

    Abstract Objectives Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol, the authors investigated whether the plasma Phytosterols (PS) relate to the body's cholesterol synthesis rate measured as non-cholesterol sterol precursors (lathosterol). Method The authors studied 38 non-obese volunteers (58±12 years; Low-Density Lipoprotein Cholesterol ‒ LDL-C ≥ 130 mg/dL) randomly assigned to consume 400 mL/day of soy milk (Control phase) or soy milk + PS (1.6 g/day) for four weeks in a double-blind, cross-over study. PS and lathosterol were measured in plasma by gas chromatography coupled to mass spectrophotometry. Results PS treatment reduced plasma total cholesterol concentration (-5.5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration), but plasma lathosterol, campesterol and sitosterol expressed per plasma cholesterol increased. Conclusions The lathosterol-to-cholesterol plasma ratio predicted the plasma cholesterol response to PS feeding. The highest plasma lathosterol concentration during the control phase was associated with a lack of response of plasma cholesterol during the PS treatment period. Consequently, cholesterol synthesis in non-responders to dietary PS being elevated in the control phase indicates these cases resist to further synthesis rise, whereas responders to dietary PS, having in the control phase synthesis values lower than non-responders, expand synthesis on alimentary PS. Responders absorb more PS than non-responders, likely resulting from responders delivering into the intestinal lumen less endogenous cholesterol than non-responders do, thus facilitating greater intestinal absorption of PS shown as increased plasma PS concentration.
  • Gathering patients and rheumatologists' perceptions to improve outcomes in idiopathic inflammatory myopathies Original Articles

    Bertoglio, Isabela M.; Abrahao, Glaucia F.; de Souza, Fernando H.C.; Miossi, Renata; de Moraes, Paloma C.; Shinjo, Samuel K.; Bonfá, Eloisa; Lopes, Michelle R. Ugolini

    Resumo em Inglês:

    Abstract Objective Therapeutic targets in Idiopathic Inflammatory Myopathies (IIM) are based on the opinions of physicians/specialists, which may not reflect the main concerns of patients. The authors, therefore, assessed the outcome concerns of patients with IIM and compared them with the concerns of rheumatologists in order to develop an IIM outcome standard set. Methods Ninety-three IIM patients, 51 rheumatologists, and one physiotherapist were invited to participate. An open questionnaire was initially applied. The top 10 answers were selected and applied in a multiple-choice questionnaire, inquiring about the top 3 major concerns. Answers were compared, and the agreement rate was calculated. Concerns were gathered in an IIM outcome standard set with validated measures. Results The top three outcome concerns raised by patients were medication side effects/muscle weakness/prevention functionality loss. The top three concerns among rheumatologists were to prevent loss of functionality/to ensure the quality of life/to achieve disease remission. Other's outcomes concerns only pointed out by patients were muscle pain/diffuse pain/skin lesions/fatigue. The agreement rate between both groups was 41%. Assessment of these parameters guided the development of an IIM standard set which included Myositis Disease Activity Assessment Visual Analogue Scale/Manual Muscle Testing/fatigue and pain Global Visual Analogue Scale/Health Assessment Questionnaire/level of physical activity. Conclusion The authors propose a novel standard set to be pursued in IIM routine follow-up, which includes not only the main patients/rheumatologist outcome concerns but also additional important outcomes only indicated by patients. Future studies are necessary to confirm if this comprehensive approach will result in improved adherence and ultimately in better assistance.
  • CLEC14A was up-regulated in hepatocellular carcinoma and may function as a potential diagnostic biomarker Original Articles

    Yan, Lang; Li, Xiang; Yuan, Yunfeng

    Resumo em Inglês:

    Abstract Objective The current work aimed to investigate the expression and potential clinical significance of C-type Lectin domain family 14 (CLEC14A) in hepatocellular carcinoma. Methods The relative expressions of CLEC14A in the Hepatocellular Carcinoma (HCC) tissue and adjacent normal tissue of 105 HCC patients were examined using RT-qPCR methods. Furthermore, Receiver Operating Characteristic (ROC) curve was drawn for exploring the diagnostic value of CLEC14A. Next, the expressions of CLEC14A in HCC cell lines and normal liver epithelial cells were compared, and the effects of knockdown of CLEC14A on the growth and apoptosis of HCC cells were examined. Results The authors found that the expression of CLEC14A was markedly increased in hepatocellular carcinoma tumors in comparison with the adjacent tissue, and the expression level of CLEC14A was positively correlated with the size and differentiation of the tumor. Moreover, results of ROC analysis showed CLEC14A might function as a sensitive diagnostic biomarker for HCC. Furthermore, CLEC14A was up-regulated in HCC cell lines, and transient over-expression of CLEC14A decreased the proliferation and increased the apoptosis of HCC cells in vitro. Conclusions Our results suggested that CLEC14A was up-regulated in HCC and might function as a potential diagnostic marker.
  • Invariant Natural Killer T-cells and their subtypes may play a role in the pathogenesis of endometriosis Original Articles

    Correa, Frederico J.S.; Andres, Marina Paula; Rocha, Tainá Pezzin; Carvalho, Ana Eduarda Z.; Aloia, Thiago P.A.; Corpa, Marcus V.N.; Kallas, Esper G.; Mangueira, Cristóvão L.P.; Baracat, Edmund C.; Carvalho, Karina I.; Abrão, Mauricio S.

    Resumo em Inglês:

    Highlights The frequency of iNKT cells in general and their subtype double-negative are related to endometriosis. The expression of IL-17 and CCR7 by iNKT cells are related to endometriosis-associated pain symptoms. iNKT cells are numerically and functionally altered in women with endometriosis.
  • Neuropathologic damage induced by radiofrequency ablation at different temperatures Original Articles

    Dong, Yu; Chen, Ying; Yao, Baoguo; Song, Peng; Xu, Ruiting; Li, Rui; Liu, Ping; Zhang, Yu; Mu, Li; Tong, Xin; Ma, Linwei; Yu, Jianjun; Su, Li

    Resumo em Inglês:

    Highlights There is a positive correlation between temperature and neuropathological damage caused by RFA at different temperatures. There is a positive correlation between nerve conduction velocity and temperature. Nerve injury occurs when the temperature reaches 67°C, and the main pathogenesis is closely related to the expression of SCN9A, SCN3B and NFASC protein in sciatic nerve tissue caused by heat transfer injury.
  • Methyl-CpG binding protein 2 is associated with the prognosis and mortality of elderly patients with hip fractures Original Articles

    Gao, Xuejian; Xue, Shan; Yang, Fuqiang; Wu, Baoling; Yu, Xiaojing; An, Baoquan

    Resumo em Inglês:

    Highlights MECP2 was downregulated in elderly patients with hip fracture. MECP2 was correlated with inflammatory factors in hip fractures. Lower MECP2 predicted poor clinical outcomes of hip fractures. Lower MECP2 predicted higher mortality and postoperative complications.
  • L1 cell adhesion molecule high expression is associated with poor prognosis in surgically resected brain metastases from lung adenocarcinoma Original Articles

    Wang, Jia-Wei; Wang, Song-Quan; Wu, Zhuo-Yi; Liu, Qi; Yuan, Qing; Cai, Hong-Qing; Wan, Jing-Hai

    Resumo em Inglês:

    Highlights Brain metastasis aberrantly expresses L1CAM. L1CAM high expression is associated with poor prognosis in brain metastases.
  • Changes in postural balance associated with a woman's aging process Original Articles

    Brech, Guilherme Carlos; Bobbio, Tatiana Godoy; Cabral, Kelem de Negreiros; Coutinho, Patrícia Mota; Castro, Leila Regina de; Mochizuki, Luis; Soares-Junior, Jose Maria; Baracat, Edmund Chada; Leme, Luiz Eugênio Garcez; Greve, Julia Maria D'Andréa; Alonso, Angélica Castilho

    Resumo em Inglês:

    Highlights Aging process increases postural oscillations, worsening the postural balance. Poor postural balance is more evident in the elderly over 80-years old. Deterioration of the postural control systems and the increased risk of falls. Important identify factors related to falls and postural balance.
  • Team emergency assessment measure (TEAM) of non-technical skills: The Brazilian Portuguese version of the TEAM tool Original Articles

    Giugni, Fernando Rabioglio; Dias, Roger Daglius; Rodrigues, Caio Godoy; Pinesi, Henrique Trombini; Scalabrini-Neto, Augusto

    Resumo em Inglês:

    Highlights The authors translated and cross-culturally adapted the TEAM tool into Brazilian Portuguese. The Brazilian Portuguese TEAM version proved to be a consistent and reliable tool.
  • IPO7 promotes pancreatic cancer progression via regulating ERBB pathway Original Articles

    Li, Ming; Xu, Dongqiang; Zhan, Yijun; Tan, Shiyun

    Resumo em Inglês:

    Highlights IPO7 remarkably enhanced pancreatic cancer cell proliferation, migration and invasion and suppressed apoptosis. IPO7 facilitated the malignant phenotype of pancreatic cancer cells by up-regulating ERBB2. Knockdown of IPO7 inhibited tumor growth and lung metastasis in vivo.
  • Novel rearrangements between different chromosomes with direct impact on the diagnosis of 5p- syndrome Original Articles

    Chehimi, Samar Nasser; Almeida, Vanessa Tavares; Nascimento, Amom Mendes; Zanardo, Évelin Aline; Oliveira, Yanca Gasparini de; Carvalho, Gleyson Francisco da Silva; Wolff, Beatriz Martins; Montenegro, Marilia Moreira; Assunção, Nilson Antônio de; Kim, Chong Ae; Kulikowski, Leslie Domenici

    Resumo em Inglês:

    Abstract Objectives Copy Number Variations (CNVs) in the human genome account for common populational variations but can also be responsible for genetic syndromes depending on the affected region. Although a deletion in 5p is responsible for a syndrome with highly recognizable phenotypical features, other chromosomal abnormalities might overlap phenotypes, especially considering that most studies in 5p use traditional cytogenetic techniques and not molecular techniques. Methods The authors have investigated 29 patients with clinical suspicion of 5p- syndrome using Chromosomal Microarray (CMA), and have gathered information on previous tests, clinical signs, symptoms, and development of the patients. Results The results showed 23 pure terminal deletions, one interstitial deletion, one deletion followed by a 3 Mb duplication in 5p, three cases of 5p deletion concomitant to duplications larger than 20 Mb in chromosomes 2, 9, and 18, and one 5p deletion with a chromosome Y deletion. CMA showed relevant CNVs not typically associated with 5p- that may have contributed to the final phenotype in these patients. Conclusions The authors have identified three novel rearrangements between chromosomes 5 and 2 (Patient 27), 5 and 18 (Patient 11), and 5 and Y (Patient 22), with breakpoints and overlapped phenotypes that were not previously described. The authors also highlight the need for further molecular investigation using CMA, in different chromosomes beyond chromosome 5 (since those cases did not show only the typical deletion expected for the 5p- syndrome) to explain discordant chromosomal features and overlapped phenotypes to unravel the cause of the syndrome in atypical cases. HIGHLIGHTS The authors The authors have described three novel rearrangements between chromosomes 5 and 2, 5 and 18, and 5 and Y with chromosomal breakpoints and overlapped phenotypes that were not previously described. One of the main atypical features for 5p- syndrome that the authors report was the presence of seizures that was found in the three patients with rearrangements between different chromosomes and in a patient with a deletion followed by duplication in 5p. The authors suggest physicians conduct further molecular investigation in the presence of atypical clinical features for patients with 5p- syndrome suspicion.
  • Role of apolipoprotein O in autophagy via the p38 mitogen-activated protein kinase signaling pathway in myocardial infarction Original Articles

    Liu, Yue; Xiong, Zhiping; Zhou, Wei; Chen, Yuxin; Huang, Qing; Wu, Yanqing

    Resumo em Inglês:

    Abstract Objectives To explore the role and possible mechanisms of action of apolipoprotein O (APOO) in autophagy in Myocardial Infarction (MI) in vivo and in vitro. Methods Differential gene expression and single Gene Set Enrichment Analysis (GSEA) were used to evaluate MI-related candidate genes. Animal and cell MI models were established. Sh-APOO, si-APOO, and SB203580 were used to inhibit the expression of APOO or p38MAPK. Western blot and qRT-PCR were used to analyze the expression levels of the target protein or mRNA. Apoptosis was observed using the TUNEL assay. The plasma concentrations of CK-MB and cTn-I in humans and mice were determined. Results In the GSE23294 dataset, APOO mRNA was highly expressed in the left ventricle of mice with MI; GSEA revealed that APOO was positively correlated with p38MAPK, autophagy, and apoptosis. The plasma concentration of APOO in patients with MI was significantly higher than that in healthy subjects. The expression of APOO, Beclin-1, LC3, and Bax in mouse and AC16 cell MI models increased, while the level of Bcl-2 decreased. After silencing the APOO gene, the expression of APOO was downregulated; meanwhile, changes in autophagy, apoptosis and myocardial cell injury were reversed in vivo and in vitro. Furthermore, autophagy was alleviated after AC16 cells were treated with SB203580. Conclusions The increased APOO expression in mouse and cell MI models may activate autophagy and apoptosis by regulating the p38MAPK signaling pathway, thus aggravating the myocardial injury. HIGHLIGHTS APOO was highly expressed in the left ventricle of mice with myocardial infarction. Increasing of APOO may activate autophagy and apoptosis in myocardial infarction. The regulation of APOO in autophagy and apoptosis was regulated by p38MAPK signaling pathway.
  • LncRNA LINC01857 drives pancreatic adenocarcinoma progression via modulating miR-19a-3p/SMOC2 Original Articles

    Lu, Yeting; Ying, Dongjian; Tian, Yuan; Ruan, Yi; Cheng, Gong; Lv, Kaiji; Zhou, Xinhua; Han, Shuo

    Resumo em Inglês:

    Abstract Objectives Emerging evidence has demonstrated that LINC01857 exerts a pivotal function in many cancers. However, its function in Pancreatic Ductal Adenocarcinoma (PDAC) still remains unclear. This study was designed to investigate the regulatory character of LINC01857 in PDAC. Methods Bioinformatic tools and databases were used to seek potential miRNAs and mRNAs. Gene expression was evaluated by Reverse Transcription quantitative real-time Polymerase Chain Reaction (RT-qPCR), and western blot was used for protein level detection. A subcellular fraction assay was done to ascertain the location of LINC01857 in PANC-1 and BxPC-3 human pancreatic cancer cells. CCK-8, EdU, wound healing and Transwell assays were performed to inquire into the influence of LINC01857, and SPARC -related Modular Calcium-binding protein-2 (SMOC2) on cell viability, proliferation, migration, and invasion, respectively. The interaction between LINC01857 and its downstream genes was explored by RNA immunoprecipitation and luciferase reporter assays. Results LINC01857 levels were significantly elevated in PDAC. Knockdown of LINC01857 significantly restrained the proliferation, migration, invasion, and Epithelial-Mesenchymal Transition (EMT) process of PDAC cells. MiR-19a-3p was a downstream target of LINC01857, and miR-19a-3p levels were significantly decreased in PDAC cells. In addition, SMOC2 expression had a negative correlation with that of miR-19a-3p, and SMOC2 was a downstream target of miR-19a-3p. Furthermore, SMOC2 upregulation partially abolished the inhibitive influence of LINC01857 downregulation on cell proliferation, migration, invasion, and the EMT process. Conclusion LINC01857 promotes malignant phenotypes of PDAC cells via upregulation of SMOC2 by interacting with miR-19a-3p. HIGHLIGHTS LINC01857 is upregulated in PAAD and promotes malignant cellular behaviors. LINC01857 interacts with miR-19a-3p to regulate SMOC2 expression. LINC01857 promotes malignant cellular phenotypes by upregulating SMOC2.
  • Adherence to the cardiac surgery checklist decreased mortality at a teaching hospital: A retrospective cohort study Original Articles

    Mejia, Omar Asdrúbal Vilca; Mendonça, Frederico Carlos Cordeiro de; Sampaio, Lucimar Aparecida Barrense Nogueira; Galas, Filomena Regina Barbosa Gomes; Pontes, Mauricio Franklin; Caneo, Luiz Fernando; Dallan, Luís Roberto Palma; Lisboa, Luiz Augusto Ferreira; Ferreira, João Fernando Monteiro; Dallan, Luís Alberto de Oliveira; Jatene, Fabio Biscegli

    Resumo em Inglês:

    Abstract Objectives To evaluate the impact of adherence to the cardiac surgical checklist on mortality at the teaching hospital. Methods A retrospective cohort study after the implementation of the cardiac surgical safety checklist in a reference hospital in Latin America. All patients undergoing coronary artery bypass surgery and/or heart valve surgery from 2013 to 2019 were analyzed. After the implementation of the project InCor-Checklist “Five steps to safe cardiac surgery” in 2015, the correlation between adherence and completeness of this instrument with surgical mortality was assessed. The EuroSCORE II was used as a reference to assess the risk of expected mortality for patients. Cross-sectional questionnaires were during the implementation of the InCor-Checklist. To perform the correlation, Pearson’s coefficient was calculated using R software. Results Since 2013, data from 8139 patients have been analyzed. The average annual mortality was 5.98%. In 2015, the instrument was used in only 58% of patients; in contrast, it was used in 100% of patients in 2019. There was a decrease in surgical mortality from 8.22% to 3.13% for the same group of procedures. The results indicate that the greater the checklist use, the lower the surgical mortality (r = 88.9%). In addition, the greater the InCor-Checklist completeness, the lower the surgical mortality (r = 94.1%). Conclusion In the formation of the surgical patient safety culture, the implementation and adherence to the InCor-Checklist “Five steps to safe cardiac surgery” was associated with decreased mortality after cardiac surgery. HIGHLIGHTS Checklists avoid human errors and are commonly used in high-reliability industries. The “InCor Checklist” was associated with decreased mortality over time. Adherence, completeness, and sustainability within public policies are necessary.
  • let-7b-5p suppresses the proliferation and migration of pulmonary artery smooth muscle cells via down-regulating IGF1 Original Articles

    Zhang, Yadi; Tang, Sihui; Yang, Wanchun; Du, Fangbing

    Resumo em Inglês:

    Abstract Objectives Some previous studies indicated that the excessive proliferation and migration of Pulmonary Artery Smooth Muscle Cells (PASMCs) could be observed in pulmonary artery intima after Pulmonary Embolism (PE) occurred. In addition, recent studies identified some miRNAs that are differentially expressed in the blood of PE patients, which might be used as a diagnostic biomarker for PE, including let-7a-5p, let-7b-5p, and miR-150-5p. Hence, the authors sought to explore the effects of let-7b-5p in PASMC proliferation and migration and the corresponding regulatory mechanism. Methods Platelet-Derived Growth Factor (PDGF) was utilized to induce the hyper-proliferation model in PASMCs. The mRNA and protein expression levels were detected by RT-qPCR and western blot, respectively. The proliferation of PASMCs was evaluated by the detection of PCNA expression, as well as CCK-8 and Edu assays. Wound healing and Transwell assays were exploited to assess the migration ability of PASMCs. The targets of let-7b-5p were predicted based on two bioinformatics online tools. Dual-luciferase and Ago2 pull-down assays were applied to confirm the interaction between let-7b-5p and IGF1. Results 40 ng/mL PDGF was selected as the optimal concentration to induce PASMCs. let-7b-5p mimics suppressed the proliferation and migration of PDGF-induced PASMCs, while let-7b-5p inhibitor led to the opposite result. In further mechanism exploration, IGF1 was predicted and confirmed as the direct target gene of let-7b-5p. The promotion role of IGF1 overexpression on the proliferation and migration of PDGF-induced PASMCs was dramatically countered by let-7b-5p mimics. Conclusion let-7b-5p prohibits the proliferation and migration of PDGF-induced PASMCs by modulating IGF1.
  • SNHG22 promotes migration and invasion of trophoblasts via miR-128-3p/ PCDH11X axis and activates PI3K/Akt signaling pathway Original Articles

    Wei, Xiaoying; Yuan, Yichong; Yang, Qiong

    Resumo em Inglês:

    Abstract Objectives Long non-coding RNAs (LncRNAs) act as an indispensable role in the Preeclampsia (PE)-related trophoblast function, while its relationship with Small Nucleolar RNA Host Gene 22 (SNHG22) remains unknown. Hence, this study aimed to investigate the roles of lncRNA SNHG22 in the Preeclampsia (PE)-related trophoblasts function and the underlying mechanism. Methods Normal placentas and placentas from PE patients were collected to detect the expression of lncRNA SNHG22. Then, trophoblasts HTR-8/Svneo and JEG-3 were purchased, cultured, and treated to investigate the roles of lncRNA SNHG22 on cell migration and invasion as well as its underlying regulatory mechanism. Results The SNHG22 was downregulated in PE patients, and it was found that SNHG22 overexpression could drive migration and invasion of trophoblasts, while SNHG22 depletion exerted a suppressive effect. Mechanistically, SNHG22 was validated to regulate microRNA-128-3p (miR-128-3p), and Protocadherin 11 X-Linked (PCDH11X) was identified as the target gene of miR-128-3p. Furthermore, it was found that SNHG22 acted as a promoter in the migration and invasion of trophoblast cells in a miR-128-3p/PCDH11X dependent manner, and SNHG22 silencing weakened the activation of PCDH11X-mediated PI3K/Akt signaling pathways through inhibiting miR-128-3p, thereby preventing migration and invasion of trophoblasts. Conclusion SNHG22 acted as a driver in the migration and invasion of trophoblasts and may be considered a candidate for the amelioration of PE.
  • Exosomal miR-152-5p and miR-3681-5p function as potential biomarkers for ST-segment elevation myocardial infarction Original Articles

    Chen, Xiaozhu; Huang, Fengrong; Liu, Yunhong; Liu, Shujun; Tan, Gangwen

    Resumo em Inglês:

    Abstract Background: The strain parameters of Real-Time Three-Dimensional Spot Tracking Echocardiography (RT3D-STE) are GLS, GAS, GRS, and GCS, while each index can significantly diagnose Acute Myocardial Infarction (AMI) patients, but none of them can distinguish between NSTEMI and STEMI. MicroRNAs (miRNAs) play essential roles in Acute Myocardial Infarction (AMI), but little is known about the value of exosome miRNA combined with RealTime Three-Dimensional Spot Tracking Echocardiography (RT3D-STE) between ST-segment Elevation Myocardial Infarction (STEMI) and Non-ST-segment Elevation Myocardial Infarction (NSTEMI). Aim: To estimate the exosomal miRNAs related to strain parameters of RT3D-STE as biomarkers for early detection of STEMI and NSTEMI. Methods: The present study collected plasma samples from thirty-four (34) patients with AMI (including STEMI and NSTEMI) and employed high-throughput sequence technology and real-time quantitative polymerase chain reaction (RT-qPCR) to identify the differentially expressed miRNAs. The Pearson correlation coefficient is used to measure the strength of a linear association between differentially expressed miRNAs and strain parameters of RT3D-STE. Results: Twenty-eight (28) differentially expressed exosomal miRNAs were universally identified between STEMI, NSTEM, and normal groups. Among them, there are 10 miRNAs (miR-152-5p, miR-3681-5p, miR-193a-5p, miR-193b-5p miR-345-5p, miR-125a-5p, miR-365a-3p, miR-4520-2-3p, hsa-miR-193b-3p and hsa-miR-5579-5p) with a Pearson correlation greater than 0.6 with RT3D-STE strain parameters. Especially, miR-152-5p and miR-3681-5p showed the most significant correlation with RT3D-STE strain parameters. Target genes of these 10 miRNAs are analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment, and they were found to be mainly involved in the cellular metabolism processes and HIF-1 signaling pathway. RT-qPCR verified the significant differential expression of miR-152-5p and miR-3681-5p between STEMI and NSTEM groups. Conclusion: RT3D-STE and exosome miRNAs can be used as a hierarchical diagnostic system in AMI. If the RT3D-STE is abnormal, the exosome miRNAs can be detected again to obtain more detailed and accurate diagnostic results between STEMI and NSTEM groups. Exosomal miR-152-5p and miR-3681-5p may serve as potential biomarkers for ST-segment elevation myocardial infarction. HIGHLIGHTS RT3D-STE and exosome miRNAs can be used as a hierarchical diagnostic system in AMI. Exosomal miR-152-5p and miR-3681-5p function as potential biomarkers for ST-segment elevation myocardial infarction.
  • The lack of knowledge on acute stroke in Brazil: A cross-sectional study with children, adolescents, and adults from public schools Original Articles

    Calderaro, Marcelo; Salles, Igor C.; Gouvêa, Gabriela B.; Monteiro, Vinícius S.; Mansur, Antonio P.; Shinohara, Henrique N.I.; Aikawa, Priscila; Umeda, Iracema I.K.; Semeraro, Federico; Carmona, Maria José C.; Böttiger, Bernd W.; Nakagawa, Naomi K.

    Resumo em Inglês:

    Abstract Objective: Stroke is an important cause of disability and death in adults worldwide. However, it is preventable in most cases and treatable as long as patients recognize it and reach capable medical facilities in time. This community-based study investigated students' stroke knowledge, Emergency Medical Services (EMS) activation, associated risk factors, warning signs and symptoms, and prior experience from different educational levels in the KIDS SAVE LIVES BRAZIL project. Methods: The authors conducted the survey with a structured questionnaire in 2019‒2020. Results: Students from the elementary-school (n = 1187, ~13 y.o., prior experience: 14%, 51% women), high-school (n = 806, ~17 y.o., prior experience: 13%, 47% women) and University (n = 1961, ~22 y.o., prior experience: 9%, 66% women) completed the survey. Among the students, the awareness of stroke general knowledge, associated risk factors, and warning signs and symptoms varied between 42%‒66%. When stimulated, less than 52% of the students associated stroke with hypercholesterolemia, smoking, diabetes, and hypertension. When stimulated, 62%‒65% of students recognized arm weakness, facial drooping, and speech difficulty; only fewer identified acute headache (43%). Interestingly, 67% knew the EMS number; 81% wanted to have stroke education at school, and ~75% wanted it mandatory. Women, higher education, and prior experience were associated with higher scores of knowing risk factors (OR = 1.28, 95% CI: 1.10‒1.48; OR = 2.12, 95% CI: 1.87‒2.40; OR = 1.46, 95% CI: 1.16‒1.83; respectively), and warning signs- symptoms (OR = 2.22, 95% CI: 1.89‒2.60; OR = 3.30, 95% CI: 2.81‒3.87; OR = 2.04, 95% CI: 1.58‒2.63; respectively). Conclusion: Having higher education, prior experience, and being a woman increases stroke-associated risk factors, and warning signs and symptoms identification. Schoolchildren and adolescents should be the main target population for stroke awareness. HIGHLIGHTS Higher education, prior experience, and being women improved the odds of identifying stroke warning signs and symptoms as associated risk factors Improving knowledge, skills, and attitude on acute stroke in the school community may represent a significant advance in public health management Future stroke awareness campaigns and educational efforts should focus on schoolchildren and adolescents, especially in low-income countries
  • Associations of systemic inflammatory markers with the risks of chronic heart failure: A case-control study Original Articles

    Liu, Zhaojun; Xv, Yingjie; Liu, Xiaozhu; Zhou, Xiaoli

    Resumo em Inglês:

    Abstract Objective: As a greater proportion of patients survived their initial cardiac insult, Chronic Heart Failure (CHF) is becoming a major cause of worldwide morbidity and mortality. However, the mechanism underlying the inflammation in patients with CHF has not yet been elaborated. This study aims to explore the associations between inflammation and CHF patients, and the predictive performance of inflammatory indicators in identifying patients with CHF. Methods: A matched case-control study was conducted by recruiting 385 patients who were diagnosed with CHF from January 2018 to December 2019 in The First Affiliated Hospital of Chongqing Medical University. Each CHF patient was matched against one control subject without CHF on the criteria of age, sex, Body Mass Index (BMI), smoking status, and comorbidities. The clinical data and systemic inflammatory indicators were compared between the two groups, independent risk factors of CHF were identified by multivariate regression analysis, and the predictive values of systemic inflammatory indicators for CHF were analyzed by Receiver Operating Characteristic (ROC) curve analysis. Results: After processed in the univariate and multivariate regression analysis models, three systemic inflammatory indicators (hs-CRP [high sensitivity C Reactive Protein], LMR [lymphocyte-to-monocyte ratio], and Monocyte-to-High-density-lipoprotein Ratio [MHR]) were considered as independent predictors of CHF, among which the hs-CRP exhibited the best predictive performance (AUC = 0.752, 95%CI 0.717‒0.786, p < 0.001), followed by LMR (AUC = 0.711, 95% CI 0.675‒0.747, p < 0.001) and MHR (AUC = 0.673, 95% CI 0.635‒0.710, p < 0.001). The three-indicator combination showed an improved diagnostic performance (AUC = 0.757, 95% CI 0.724‒0.791, p < 0.001). In addition, the results of subgroup comparisons demonstrated that hs-CRP and MHR were associated with the severity of CHF (p < 0.001). Conclusions: The systemic inflammatory indicators such as hs-CRP, LMR, and MHR were independently correlated with the attack of CHF and might be the complementary markers of the diagnosis of CHF. HIGHLIGHTS Two novel inflammation-related markers, LMR and MHR are associated with Chronic Heart Failure (CHF). LMR and MHR were first proposed to be the predictors of a diagnosis of CHF in this study, which suggested that inflammation was associated with CHF, and anti-inflammation therapy might be a potential target for future therapeutic interventions. Compared with special inflammatory indicators such as TNF or IL-1, LMR and MHR are routinely measured in clinical practice and less time-consuming, which makes them suitable for popularization.
  • Importance of detection of Strongyloides stercoralis DNA in fecal samples from patients with type 2 diabetes mellitus Original Articles

    Mazzaro, Marcia Carolina; Santos, Émelin Alves dos; Melo, Gessica Baptista de; Marques, Priscila Duarte; Souza, Laura Vilela; Elias-Oliveira, Jefferson; Silva, Bruna Campos da; Gryschek, Ronaldo Cesar Borges; Paula, Fabiana Martins de; Rodrigues, Rosângela Maria

    Resumo em Inglês:

    Abstract Objective: The association between diabetes and Strongyloides infection remains controversial. This study aimed to detect Strongyloides stercoralis DNA in the feces of patients with Diabetes Mellitus type 2 (DM2). Methods: Fecal samples were analyzed via the Lutz, Rugai, and agar plate culture methods. PCR amplification was performed using two targets (PCR-genus and PCR-species) located on the S. stercoralis 18S ribosomal. Results: The positivity for S. stercoralis using parasitological methods was 1.1%. PCR-genus (14.13%) demonstrated a higher positivity than PCR-species (9.78%). Conclusion: The results confirm the greater positivity of the molecular diagnosis in relation to parasitological methods, reinforcing its use as an additional tool for the diagnosis of S. stercoralis infection in patients with DM2 living in endemic areas for this helminthiasis. HIGHLIGHTS Positivity for strongyloidiasis in coproscopic exam was low in diabetic patients. PCR is more sensitive for detecting S. stercoralis infection in diabetic patients. Molecular diagnosis is an important tool for the detection of S. stercoralis.
  • Frequency and factors associated with hospital readmission after COVID-19 hospitalization: the importance of post-COVID diarrhea Original Articles

    Freire, Maristela Pinheiro; Oliveira, Maura Salaroli; Magri, Marcello Mihailenko Chaves; Tavares, Bruno Melo; Marinho, Igor; Nastri, Ana Catharina De Seixas Santos; Busatto Filho, Geraldo; ,; Levin, Anna S.

    Resumo em Inglês:

    Abstract Purpose: The aim of this study was to describe the incidence and risk factors for hospital readmission and infection during the months after COVID-19 hospital admission. Methods: This prospective study included adult patients who were hospitalized due to COVID-19 and had been discharged from April 2020 to August 2020. All patients had a medical evaluation with a structured questionnaire 6 to 11 months after hospital admission. The authors included only patients with confirmed COVID-19 by RT-PCR. Patients with pregnant/postpartum women, with a proven COVID-19 reinfection or incapable of answering the questionnaire were excluded. Results: A total of 822 patients completed the follow-up assessment, and 68% reportedat least one recurrent symptom related to COVID-19. The most frequent symptom was myalgia (42%). Thirty-two percent of patients visited an emergency room after COVID-19 hospitalization, and 80 (10%) patients required re-hospitalization. Risk factors for hospital readmission were orotracheal intubation during COVID-19 hospitalization (p = 0.003, OR = 2.14), Charlson score (p = 0.002, OR = 1.21), congestive heart failure (p = 0.005, OR = 2.34), peripheral artery disease (p = 0.06, OR= 2.06) and persistent diarrhea after COVID-19 hospitalization discharge (p= 0.02, OR = 1.91). The main cause of hospital readmission was an infection, 43 (54%). Pneumonia was the most frequent infection (29%). Conclusions: The presence of symptoms after six months of COVID-19 diagnosis was frequent, and hospital readmission was relatively high. HIGHLIGHTS 32% of the patients visited an emergency room after COVID-19 hospitalization. The rate of hospital readmission after COVID-19 hospitalization is high, in the present sample 10% of patients needed a second hospitalization in 6-months Patients with persistent diarrhea after COVID-19 discharge had two times more chance to have another hospitalization in the next 6-months.
  • The dual effect of acetate on microglial TNF-α production Original Articles

    Fragas, Matheus Garcia; Oliveira, Daniel May de; Hiyane, Meire Ioshie; Braga, Tarcio Teodoro; Camara, Niels Olsen Saraiva

    Resumo em Inglês:

    Abstract Introduction: Short-Chain Fatty Acids (SCFA) are products of intestinal microbial metabolism that can reach the brain and alter microglia in health and disease contexts. However, data are conflicting on the effect of acetate, the most abundant SCFA in the blood, in these cells. Objective: The authors aimed to investigate acetate as a modulator of the inflammatory response in microglia stimulated with LPS. Method: The authors used an immortalized cell line, C8-B4, and primary cells for in vitro treatments with acetate and LPS. Cell viability was analyzed by MTT, cytokine by RT-PCR, ELISA, and flow cytometry. The authors also performed in vivo and in silico analyses to study the role of acetate and the TNF-α contribution to the development of Experimental Autoimmune Encephalomyelitis (EAE). Results: Acetate co-administered with LPS was able to exacerbate the production of pro-inflammatory cytokines at gene and protein levels in cell lines and primary culture of microglia. However, the same effects were not observed when acetate was administered alone or as pretreatment, prior to the LPS stimulus. Additionally, pharmacological inhibition of histone deacetylase concomitantly with acetate and LPS led to decreased TNF-α production. In silico analysis showed a crucial role of the TNF-α pathway in EAE development. Moreover, acetate administration in vivo during the initial phase of EAE led to a better disease outcome and reduced TNF-α production. Conclusion: Treatment with acetate was able to promote the production of TNF-α in a concomitant LPS stimulus of microglia. However, the immune modulation of microglia by acetate pretreatment may be a component in the generation of future therapies for neurodegenerative diseases. HIGHLIGHTS Acetate was able to exacerbate the production of TNF-α in microglia. Acetate administered as pre-treatment to LPS acts as an anti-inflammatory. Histone deacetylase decreased TNF-α production in Acetate- and LPS-treated cells. Depending on the time of administration, Acetate modulates microglia’s activation. Acetate may threaten neurodegenerative and neuropsychiatric diseases.
  • Quality of life in patients with malignant pleural effusion treated with an indwelling pleural catheter in an emerging country Original Articles

    Lauricella, Leticia Leone; D’Ambrosio, Paula Duarte; Costa, Priscila Berenice da; Augusto, Marcia Cristina; Pêgo-Fernandes, Paulo Manuel; Terra, Ricardo Mingarini

    Resumo em Inglês:

    Abstract Background: The use of Indwelling Pleural Catheter (IPC) in the care of patients with Malignant Pleural Effusion (MPE) is well established, however studies involving public health systems of low and middle-income countries are still lacking. This study aimed to determine the effect of IPC on the respiratory symptoms and Quality of Life (QoL) of patients with MPE in the setting of a Brazilian public health system. Methods: From August 2015 to November 2019, patients with MPE underwent IPC placement and were prospectively followed. QoL and respiratory symptoms were assessed by the EORTC questionnaires (QLQ-30; LC13) and Visual Analogue Scale (VAS), respectively, at pre-treatment, 30 , and 60 days after IPC placement. Results: 56 patients were enrolled with 57 catheters inserted. The mean age was 63 (23‒88) years, of which 17 (30%) were men and 39 (70%) were women. Breast 24 (42%) and lung 21 (37%) were the main primary neoplasms. Cellulitis was the most common complication and all patients recovered with appropriate antimicrobial therapy. QoL did not change significantly over time, however, the VAS showed a significant improvement in dyspnea (+1.2: -0.5; p = 0.001). Conclusion: IPC relieves respiratory symptoms without compromising the QoL, with a low complication rate. It represents a suitable option for patients with MPE and short LE in an emerging country. HIGHLIGHTS Indwelling pleural catheter represents a suitable option for patients with malignant pleural effusion and short life expectancy. It relieves respiratory symptoms without compromising the quality of life, and the complication rate is low, even in an emerging country, with a low socioeconomic and under-educated patient population. The rate of spontaneous pleurodesis was 45%. The analysis of the visual analog scale showed significant control of dyspnea (p = 0.001), but pain and quality of life did not change significantly.
  • Rat thyroid graft transplantation after cryopreservation with scintigraphic standardization for an experimental study Original Articles

    Schanaider, Alberto; Barboza, Thiago; Vasconcellos, Marcel; Gutfilen-Schlesinger, Gabriel; Souza, Sergio Augusto Lopes de

    Resumo em Inglês:

    Abstract Purpose: Budget cuts among other factors undermine the use of state-of-the-art equipment by many research groups. This doesn’t mean that their scientific data are not reliable or top-notch. Resort to adaptations is a recurrent need in their reality. The aim of this study was to assess whether scintigraphy with 99mTcO4 is effective in evaluating the functionality of thyroid grafts after cryopreservation in rats. Material and methods: 24 rats were randomly distributed into 3 groups: Control Group (CG), without surgical procedure, Hypothyroidism Group (HTG), submitted to total thyroidectomy, and Transplanted Group (TG), with total thyroidectomy and cryopreservation of the thyroid gland for 7 days followed by grafting of a thyroid lobe. A protocol using a gamma camera imaging was conducted fourteen weeks after transplantation, and the whole body 99mTc, focusing on the topic of heterotopic thyroid uptake was evaluated. Results: The images acquired had good quality with no noise and artifacts that could jeopardize its analysis. On the 14th day, HTG displayed no thyroid uptake, and the TG had a clear uptake of the thyroid graft in the topography of the biceps femoris muscle. Presented data also showed that both equipment spatial resolution and alignment (4.375 mm) did not interfere with the physiological uptake of 99mTc by the thyroid graft. Conclusion: The viability and functionality of cryopreserved thyroid autotransplantation in rats who underwent total thyroidectomy were successfully accessed by the scintigraphy protocol developed. HIGHLIGHTS Adaptations in validated methods are a recurrent trend due to limited budgets which does not diminish their functionality. Scintigraphy with 99mTcO4 is effective in evaluating the functionality of thyroid grafts after cryopreservation in rats. It is possible to adapt human SPECT for other animals for clinical and research purposes.
  • Gene expression profile in experimental frozen-thawed ovarian grafts treated with scaffold-base delivery of adipose tissue-derived stem cells Original Articles

    Damous, Luciana Lamarao; Shiroma, Marcos Eiji; Carvalho, Ana Elisa Teofilo Saturi de; Soares Jr, Jose Maria; Krieger, Jose Eduardo; Baracat, Edmund C.

    Resumo em Inglês:

    Abstract Purpose: Gelfoam scaffold is a feasible and safe non-invasive technique for Adipose tissue-derived Stem Cell (ASC)-delivery in the treatment of frozen-thawed ovarian autografts. This study seeks to analyze the genes expression profile of rat frozen-thawed ovarian autografts treated with scaffold-based delivery of adipose tissue-derived stem cells. Methods: Eighteen adult Wistar rats were distributed into three groups: Control (frozen-thawed only); Group 1 (Gl) and Group 2 (G2) (frozen-thawed ovaries treated with culture medium or ASC, respectively). Both treatments were performed immediately after autologous retroperitoneal transplant with scaffold-based delivery. The ovarian grafts were retrieved 30 days after transplantation. Quantitative gene expression (qPCR) for apoptosis, angiogenesis, and inflammatory cytokines (84 genes in each pathway) were evaluated by RT-PCR. Graft morphology (HE), apoptosis (cleaved-caspase-3), neoangiogenesis (VEGF), and cellular proliferation (Ki-67) were assessed. Results: In grafts treated with ASC, the apoptosis pathway showed the highest number of genes over-regulated — 49 genes — compared to inflammation cytokines and angiogenesis pathway — 36 and 23 genes respectively, compared to grafts treated with culture medium. Serpinb5 family was highlighted in the angiogenesis pathway and Cxcl6 in the inflammation cytokines pathway. In the apoptosis pathway, the most over-regulated gene was Cap-sasel4. ASC treatment promoted the reduction of cleaved caspase-3 in the theca internal layer and increased cell proliferation by Ki-67 in the granulosa layer without altering VEGF. A mild inflammatory infiltrate was observed in both groups. Conclusion: ASC therapy in rat frozen-thawed ovarian autografts promoted an abundance of genes involved with apoptosis and inflammatory cytokines without compromising the ovary graft morphology and viability for short time. Further studies are necessary to evaluate the repercussion of apoptosis and inflammation on the graft in the long term. HIGHLIGHTS The scaffold-based delivery therapy with adipose tissue-derived stem cells in the rat ovarian autografts seems to be the best option when compared to direct injection or systemic route. Ovarian grafts treated with adipose tissue-derived stem cells showed the highest number of genes over-regulated in the apoptosis pathway, compared to inflammation cytokines and angiogenesis pathway. Capsase14 was the most over-regulated gene in the apoptosis pathway. The treatment with adipose tissue-derived stem cells in ovarian grafts treated didn’t compromise the ovary graft morphology and viability for short time.
  • Absence of neutralizing antibodies against the Omicron SARS-CoV-2 variant in convalescent sera from individuals infected with the ancestral SARS-CoV-2 virus or its Gamma variant Original Articles

    Villas-Boas, Lucy Santos; Paula, Anderson Vicente de; Silva Jr., Almir Ribeiro da; Paiao, Heuder Gustavo Oliveira; Tozetto-Mendoza, Tania Regina; Manuli, Erika Regina; Leal, Fábio Eudes; Ferraz, Andrea de Barros Coscelli; Sabino, Ester Cerdeira; Bierrenbach, Ana Luiza; Witkin, Steven Sol; Mendes-Correa, Maria Cassia

    Resumo em Inglês:

    Abstract Objectives: The aim of the present study was to evaluate if neutralizing antibody responses induced by infection with the SARS-CoV-2 strain that was dominant at the beginning of the pandemic or by the Gamma variant was effective against the Omicron variant. Methods: Convalescent sera from 109 individuals, never exposed to a SARS-CoV-2 vaccine, who had mild or moderate symptoms not requiring hospitalization following either a documented SARS-CoV-2 ancestral strain infection or a Gamma variant infection, were assayed for in vitro neutralizing antibody activity against their original strains and the Omicron variant. Results: Following an infection with the ancestral strain, 56 (93.3%), 45 (77.6%) and 1 (1.7%) serum sample were positive for neutralizing antibodies against the ancestral, Gamma variant, and Omicron variant, respectively. After infection with the Gamma variant, 43 (87.8%) and 2 (4.1%) sera were positive for neutralizing antibodies against the Gamma and Omicron variants, respectively. Conclusions: Neutralizing antibodies generated following mild or moderate infection with the SARS-CoV-2 ancestral strain or the Gamma variant are not protective against the Omicron variant. HIGHLIGHTS Individuals previously infected with SARS-CoV-2 ancestral strain do not develop neutralizing antibodies against the Omicron variant. Omicron variant escapes immune response after SARS CoV-2 previous infection with the SARS CoV-2 Gamma variant. Individuals previously infected with SARS-CoV-2 ancestral strain or with SARS-CoV-2 Gamma variant will likely have little protection if subsequently exposed to the Omicron variant.
  • miR-146b suppresses LPS-induced M1 macrophage polarization via inhibiting the FGL2-activated NF-κB/MAPK signaling pathway in inflammatory bowel disease Original Articles

    Pan, Yang; Wang, Dan; Liu, Fan

    Resumo em Inglês:

    Abstract Objectives: M1 macrophage polarization and phenotype in Inflammatory Bowel Disease (IBD) are common biological responses. Method: Herein, IBD mice models were constructed and macrophages were derived. Results: It was discovered that microRNA-146b (miR-146b) was downregulated in IBD mice and Lipopolysaccharide (LPS)-induced macrophages. Moreover, the inhibitory role of overexpressed miR-146b in reducing the inflammation level and blocking M1 macrophage polarization was confirmed. Further investigation indicated that Fibrinogen Like 2 (FGL2) acted as the target gene of miR-146b, and FGL2 mediated activation of NLRP3, NF-κB-p65, and p38-MAPK. More importantly, it was validated that miR-146b could ameliorate inflammatory pheno-type and prevent M1 macrophage polarization via inhibiting FGL2 in vitro, and miR-146b overexpression alleviated the intestinal injury of IBD mice in vivo. Conclusions: Overall, it is potential to use miR-146b for the amelioration of IBD. HIGHLIGHTS miR-146b was downregulated in Inflammatory Bowel Disease (IBD) mice and LPS-induced macrophages. Fibrinogen Like 2 (FGL2) was identified as the target gene of miR-146b. miR-146b ameliorated the inflammation and blocked M1 macrophage polarization via inhibiting FGL2. miR-146b ameliorated the symptoms and pathological injury of IBD via inhibiting FGL2.
  • Decannulation: a retrospective cohort study of clinical and swallowing indicators of success Original Articles

    Escudero, Carina; Sassi, Fernanda Chiarion; Medeiros, Gisele Chagas de; Lima, Maíra Santilli de; Cardoso, Paulo Francisco Guerreiro; Andrade, Claudia Regina Furquim de

    Resumo em Inglês:

    Abstract Objective: To investigate the clinical and swallowing indicators related to a successful decannulation process during the hospital stay. Methods: A retrospective cohort clinical study. The study sample comprised a heterogeneous patient population who had submitted to a tracheostomy procedure in a tertiary hospital. Patients were divided into two groups (dec-annulated vs. non-decannulated) and compared not only in terms of demographic and clinical data but also the results of a swallowing assessment and intervention outcome. Results: Sixty-four patients were included in the present study: 25 (39%) who had been successfully decannulated, and 39 (61%) who could not be decannulated. Between-group comparisons indicated that both groups presented similar clinical and demographic characteristics. The groups also presented similar swallowing assessment results prior to intervention. However, significant differences were observed regarding the time to begin swallowing rehabilitation. The decannulated group was assessed nine days earlier than the non-decannulated group. Other significant differences included the removal of the alternate feeding method (72.0% of decannulated patients vs. 5.1% of non-decannulated patients) and the reintroduction of oral feeding (96.0% of decannulated patients vs. 41.0% of non-decannulated patients) and functional swallowing level at patient disclosure. The non-decannulated patient group presented higher death rates at disclosure. Conclusion: The results of the present study indicated that the following parameters were associated with a successful decannulation process: early swallowing assessment, swallowing rehabilitation, and improvement in the swallowing functional level during the hospital stay. The maintenance of low swallowing functional levels was found to be negatively associated with successful decannulation. HIGHLIGHTS Deccanulation indicators were investigated in patients who were submitted to a tracheostomy procedure. Early swallowing evaluation and rehabilitation were associated with a successful decannulation process. Low swallowing functional levels were negatively associated with the success of decannulation.
  • Risk factors for oxygen requirement in hospitalized pregnant and postpartum women with COVID-19 Original Articles

    Baptista, Fernanda Spadotto; Paganoti, Cristiane Freitas; Gomez, Ursula Trovato; Peres, Stela Verzinhasse; Malbouisson, Luiz Marcelo; Brizot, Maria de Lourdes; Francisco, Rossana Pulcineli Vieira

    Resumo em Inglês:

    Abstract Objective: To identify risk factors for Oxygen (O2) needs in pregnant and postpartum women with COVID-19. Methods: Prospective cohort involving pregnant women hospitalized with COVID-19 from April to October 2020. The oxygen need was analyzed regarding risk factors: demographic characteristics, clinical and laboratory parameters at hospital admission, and chest Computer Tomography (CT) findings. Poisson univariate analysis was used to estimate the Relative Risk (RR) and 95% Confidence Intervals. Results: 145 patients, 80 who used and 65 who did not use O2, were included. Body mass index ≥ 30, smoking, and chronic hypertension increased the risk of O2 need by 1.86 (95% CI 1.10–3.21), 1.57 (95% CI 1.16‒2.12), and 1.46 (95% CI 1.09‒1.95), respectively. Patients who were hospitalized for COVID-19 and for obstetric reasons had 8.24 (95% CI 2.8‒24.29) and 3.44 (95% CI 1.05‒11.31) times more use of O2 than those admitted for childbirth and abortion. Respiratory rate ≥ 24 breaths/min and O2 saturation < 95% presented RR for O2 requirements of 2.55 (1.82‒3.56) and 1.68 (95% CI 1.27-2.20), respectively. Ground Glass (GG) < 50% and with GG ≥ 50%, the risk of O2 use were respectively 3.41-fold and 5.33-fold higher than in patients who haven’t viral pneumonia on CT. The combination of C-reactive protein ≥ 21 mg/L, hemoglobin < 11.0 g/dL, and lymphopenia < 1500 mm3 on hospital admission increased the risk of O2 use by 4.97-times. Conclusions: In obstetric patients, clinical history, laboratory, clinical and radiological parameters at admission were identified as a risk for O2 need, selecting the population with the greatest chance of worsening. HIGHLIGHTS In unvaccinated pregnant and postpartum women, any need for oxygen supply increases the risk of invasive ventilation. Obesity, smoking and chronic arterial hypertension proved to be risk factors for the use of oxygen in pregnant and postpartum women with COVID-19. The combination of C-reactive protein ≥ 21 mg/L, hemoglobin < 11.0 g/dL, and lymphopenia < 1500 mm on hospital admission and the presence of ground glass ≥ 50% in computer tomography increased the risk of O2 use by 4.97 and 5.33 times respectively in pregnant and postpartum women with COVID-19.
  • Impact of SARS-CoV-2 on pregnancy and neonatal outcomes: An open prospective study of pregnant women in Brazil Original Articles

    Gomez, Ursula Trovato; Francisco, Rossana Pulcineli Vieira; Baptista, Fernanda Spadotto; Gibelli, Maria Augusta B.C.; Ibidi, Silvia Maria; Carvalho, Werther Brunow de; Paganoti, Cristiane de Freitas; Sabino, Ester Cerdeira; Silva, Lea Campos de Oliveira da; Jaenisch, Thomas; Mayaud, Philippe; Brizot, Maria de Lourdes; ,

    Resumo em Inglês:

    Abstract Objectives: To determine the incidence and risk of adverse obstetric and neonatal outcomes according to SARS-CoV-2 infection severity in pregnant women. Method: Open prospective study of pregnant women tested for SARS-CoV-2 by serological and molecular assays during pregnancy or delivery in two hospitals in Sao Paulo, Brazil from April 12, 2020, to February 28, 2021. Five groups were considered for analysis: C0, negative COVID-19 results and no COVID-19 symptoms; C1, positive COVID-19 results, and no symptoms; C2, positive COVID-19 results with mild symptoms; C3, positive COVID-19 results with moderate symptoms; and C4, positive COVID-19 results with severe symptoms. The association between obstetric and neonatal outcomes and COVID-19 severity was determined using multivariate analysis. Results: 734 eligible pregnant women were enrolled as follows: C0 (n = 357), C1 (n = 127), C2 (n = 174), C3 (n = 37), and C4 (n = 39). The following pregnancy and neonatal outcomes were associated with severe COVID-19: oligohydramnios (adjusted Odds Ratio [aOR] = 6.18; 95% CI 1.87‒20.39), fetal distress (aOR = 4.01; 95% Confidence Interval [CI] 1.84‒8.75), preterm birth (aOR = 5.51; 95% CI 1.47‒20.61), longer hospital stay (aOR = 1.66; 95% CI 1.36‒2.02), and admission to the neonatal intensive care unit (aOR = 19.36; 95% CI, 5.86‒63.99). All maternal (n = 6, 15.4%, p < 0.001) and neonatal (n = 5, 12.5%, p < 0.001) deaths and most fetal deaths (n = 4, 9.8%, p < 0.001) occurred in C4 group. Moderate COVID-19 was associated with oligohydramnios (aOR = 6.23; 95% CI 1.93‒20.13) and preterm birth (aOR = 3.60; 95% CI 1.45‒9.27). Mild COVID-19 was associated with oligohydramnios (aOR=3.77; 95% CI 1.56‒9.07). Conclusion: Adverse pregnancy and neonatal outcomes were associated with maternal symptomatic COVID-19 status, and risk increased with disease severity. HIGHLIGHTS COVID-19 increases the rates of adverse pregnancy and neonatal outcomes. Serious cases are associated with oligohydramnios, fetal distress, prematurity, neonatal ICU admission, maternal and neonatal deaths. The maternal clinical status dictates obstetric and neonatal outcomes.
  • Expression of ezrin protein and phosphorylated ezrin in pelvic endometriotic lesions Original Articles

    Peloggia, Alessandra; Andres, Marina Paula; Abrão, Mauricio Simões

    Resumo em Inglês:

    Abstract Objective: To evaluate the expression of Ezrin and Phosphorylated Ezrin (Phospho-Ezrin) in endometriosis lesions and its relation to the menstrual cycle phase, stage of endometriosis, histological classification, and clinical symptoms. Material and methods: The authors conducted a retrospective study, with endometriotic lesions collected from women with endometriosis (n = 57) who underwent laparoscopy from 2017 to 2018. The expression of Ezrin and Phosphorylated Ezrin proteins was analyzed by immunohistochemistry. Results: All the endometriotic lesions contained immunostaining for Ezrin in the glands. Phosphorylated Ezrin was expressed in the stroma of all endometriotic lesions. There was no difference in the Ezrin and Phosphorylated Ezrin’s expression in the retrocervical, ovarian, superficial, and intestinal lesions in the same patient. Dysmenor-rhea, dyspareunia, acyclic pain, infertility, and dysuria were similar in the three groups of Ezrin staining. There was an inversely proportional relationship between severe dyschezia and Ezrin’s intensity, being 66.7% of Ezrin 1 (weak intensity), 36.7 Ezrin 2 (moderate intensity), and 10.0% of Ezrin 3 (p = 0.013). Regarding Phospho-Ezrin there wasn’t a significant difference between all the analyzed variables. Histological classification and menstrual cycle phase had also no significant difference between Ezrin and Phospho-Ezrin immunostaining. Conclusion: Ezrin protein and Phospho-Ezrin can be considered important markers to elucidate the mechanisms related to migration and attachment of endometriotic lesions. It is still unclear if Ezrin and Phospho-Ezrin are a cause or consequence of endometriosis. Further studies comparing different types of lesions and eutopic endometrium are necessary to elucidate the role of these proteins in the pathogenesis of endometriosis. HIGHLIGHTS The implantation of endometrial cells in the pelvic cavity has been related to some factors such as a receptive environment that allows the implantation and proliferation of these cells. Several studies have shown the participation of the Ezrin protein in the process of invasion of malignant cells. The expression of Ezrin and its activated form was observed in endometriotic lesions providing great evidence that these proteins can play an important role in the migration and attachment of endometriotic lesions.
  • Intra-articular triamcinolone hexacetonide injections in hands osteoarthritis – A double-blinded randomized controlled trial with a one year follow-up Original Articles

    Paschoal, Natalia de Oliva Spolidoro; Natour, Jamil; Machado, Flavia Soares; Oliveira, Hilda Alcântara Veiga de; Fernandes, Artur da Rocha Correa; Furtado, Rita Nely Vilar

    Resumo em Inglês:

    Abstract Objective: to evaluate the effectiveness of triamcinolone Hexacetonide (TH) Intra-Articular Injection (IAI) in hand Interphalangeal Joints (IP) of Osteoarthritis (OA) patients to improve pain and joint swelling; improve function, goniometry, and grasping force, and assess IAI influence on radiographic evolution over 1-year. Methods: A randomized, double-blind study. 60 patients who underwent IAI at the most symptomatic IP joint were randomly assigned to receive TH+Lidocaine (LD) (TH/LD group) or just LD (LD group). Patients were assessed blindly for 1-year, at baseline and 1, 4, 8, 12, and 48 weeks. The following variables were assessed: articular pain and swelling, AUSCAN and COCHIN functional questionnaires, grip and pinch strength, goniometry, perception of improvement, acetaminophen consumption, and simple radiography. Repeated-measures ANOVA test was used to analyze the intervention response. Results: Sixty patients completed the follow-up. There were nine missed assessments. 97% were women; mean age of 61-years (SD = 8.2), and approximately 5-years of disease (SD = 3.6). Half of the patients present radiographic classification Kellgren and Lawrence (KL) grades I and II, and the other half grades III and IV. The two groups evolved similarly at 48-weeks. TH/LD group had a better evaluation in joint swelling and acetaminophen consumption (p = 0.04 and p < 0.001, respectively) at 48-weeks. Radiographically there was no statistical difference between groups (KL, p = 0.564; erosive OA, p = 0.999; worsening, p = 0.573). Conclusion: The IAI IP hands OA is effective for the improvement of joint swelling and decrease of analgesic consumption and does not influence the radiographic evolution of the injected joint.
  • Cognitive-behavioral group therapy for women with hypoactive sexual desire: A pilot randomized study Original Articles

    Lerner, Theo; Bagnoli, Vicente Renato; Pereyra, Elsa Aida Gay de; Fonteles, Lucivanda Pontes; Sorpreso, Isabel Cristina Esposito; Soares Júnior, José Maria; Baracat, Edmund Chada

    Resumo em Inglês:

    Abstract Background: Hypoactive Sexual Desire Disorder (HSDD) is a very prevalent sexual problem, with limited options for treatment. Given that psychological factors are major contributors to the disorder, a therapy such as Cognitive-Behavioral Therapy (CBT) may be useful to treat HSDD. Objective: To evaluate the effects of group CBT on women with HSDD. Method: Clinical trial randomized study with 106 women diagnosed with HSDD, who were divided as follows: Group 1 (n = 53) underwent group CBT for 8-weeks, and Group 2 (n = 53), were put on a waiting list and used as a control group. Sexual function was assessed by the Female Sexual Quotient (FSQQ) at the initial interview and after 6-months. Mann Whitney test was used for group comparison. Main Outcome Measures: demographics, education, sexual history, FSQQ and its domains for sexual function assessment. Results: Both groups had similar characteristics regarding sexual response, self-image, and relationship with a partner at the initial interview. Women undergoing therapy showed significant improvement in sexual function when compared with the control group. The overall FSQQ result showed an average growth of 18.08 points (95% CI 12.87‒23.28) for the therapy group against a decrease of 0.83 points (95% CI 3.43‒1.77) for controls (p < 0.001). The five domains of the questionnaire also exhibited significant improvement in the therapy group: desire and interest (p = 0.003), foreplay (p = 0.003), excitation and tuning (p < 0.001), comfort (p < 0.001), and orgasm and satisfaction (p < 0.001). Conclusion: Group CBT was shown to be an effective tool for treating HSDD.
  • Ambulation capacity, age, immunosuppression, and mechanical ventilation are risk factors of in-hospital death in severe COVID-19: a cohort study Original Articles

    Silva, Erika Christina Gouveia e; Schmitt, Ana Carolina Basso; Godoy, Caroline Gil de; Gambeta, Amislaine Cristina; Carvalho, Celso Ricardo Fernandes de; Fu, Carolina; Tanaka, Clarice; Toufen Junior, Carlos; Carvalho, Carlos Roberto Ribeiro de; Pompeu, José Eduardo

    Resumo em Inglês:

    Abstract Importance: Despite ambulation capacity being associated with a decreased level of physical activity and survival may be influenced by the functional capacity, studies have not addressed the association between ambulation capacity and death in patients hospitalized by COVID-19. Objective: To verify the functional, clinical, and sociodemographic risk factors associated with in-hospital death in individuals with severe COVID-19. Methods: It is a cohort retrospective study performed at a large tertiary hospital. Patients 18 years of age or more, of both sexes, hospitalized due to severe COVID-19 were included. Cases with dubious medical records and/or missing essential data were excluded. Patients were classified according to their ambulation capacity before the COVID-19 infection. Information regarding sociodemographic characteristics, in-hospital death, total hospital stays, Intensive Care Unit (ICU) stays, and the necessity of Mechanical Ventilation (MV) were collected from medical records and registered in a RedCap database. Multiple logistic regression analysis was used to identify possible factors associated with the in-hospital death rate. Results: Data from 1110 participants were included in the statistical analysis. The median age of the patients was 57 (46‒66) years, 58.42% (n = 590) were male, and 61.73% (n = 602) were brown or black. The case fatality rate during hospitalization was 36.0% (n = 363). In-hospital death was associated with ambulation capacity; dependent ambulators (OR = 2.3; CI 95% = 1.2-4.4) and non-functional ambulation (OR = 1.9; CI 95% = 1.1-3.3), age [older adults (OR = 3.0; CI 95% = 1.9‒4.), ICU stays (OR = 1.4; CI 95% = 1.2‒1.4), immunosuppression (OR = 5.5 CI 95% = 2.3‒13.5) and mechanical ventilation (OR = 27.5; CI 95% = 12.0-62.9). Conclusion and relevance: Decreased ambulation capacity, age, length of ICU stay, immunosuppression, and mechanical ventilation was associated with a high risk of in-hospital death due to COVID-19.
  • Impact of ERT and follow-up of 17 patients from the same family with a mild form of MPS II Original Articles

    Stephan, Bruno de Oliveira; Quaio, Caio Robledo; Spolador, Gustavo Marquezani; Paula, Ana Carolina de; Curiati, Marco Antonio; Martins, Ana Maria; Leal, Gabriela Nunes; Tenorio, Artur; Finzi, Simone; Chimelo, Flavia Teixeira; Matas, Carla Gentile; Honjo, Rachel Sayuri; Bertola, Debora Romeo; Kim, Chong Ae

    Resumo em Inglês:

    Abstract Background: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2- Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease. Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure. Nevertheless, subsequent to his tragic death, 16 affected male relatives were detected after biochemical tests identifying the low or absent activity of the IDS enzyme and confirmed by molecular analysis of the IDS gene. Following diagnosis, different options of treatment were chosen: 6 patients started ERT with Elaprase® (Idursulfase) soon after, while the other 10 remained without ERT. Eventually, 4 patients in the latter group began ERT with Hunterase® (Idursulfase Beta). None presented adverse effects to either form of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within the same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients were alive with an independent lifestyle. Conclusion: Here, the authors report the variable progress of the disease with and without ERT in a large Brazilian family with a slowly progressive form of MPS II, harboring the same missense variant in the IDS gene.
  • Resveratrol attenuates chronic pulmonary embolism-related endothelial cell injury by modulating oxidative stress, inflammation, and autophagy Original Articles

    Liu, Xiaopeng; Zhou, Haiying; Hu, Zhixiong

    Resumo em Inglês:

    Abstract Objectives: Due to Pulmonary Artery Endothelial Cell (PAEC) dysfunction, Pulmonary Hypertension (PH) persists even after the Pulmonary Embolism (PE) has been relieved. However, the mechanism behind this remains unclear. Method: Here, the authors incubated Human PAECs (HPAECs) with thrombin to simulate the process of arterial thrombosis. Results: CCK8 results showed a decrease in the viability of HPAECs after thrombin incubation. In addition, the expression of Tissue Factor (TF), Monocyte Chemoattractant Protein 1 (MCP-1), VCAM-1, ICAM-1, cleaved cas-pase 3, cleaved caspase 9, and Bax protein were all increased after thrombin incubation, while Bcl-2 was decreased. The effects of 3-MA treatment further suggested that autophagy might mediate the partial protective effects of Resveratrol on HPAECs. To observe the effects of Resveratrol in vivo, the authors established a Chronic Thromboembolic Pulmonary Hypertension (CTEPH) model by repeatedly injecting autologous blood clots into a rat’s left jugular vein. The results exhibited that Mean Pulmonary Arterial Pressure (mPAP) and vessel Wall Area/ Total Area (WA/TA) ratio were both decreased after Resveratrol treatment. Moreover, Resveratrol could reduce the concentration and activity of TF, vWF, P-selectin, and promote these Superoxide Dismutase (SOD) in plasma. Western blot analysis of inflammation, platelet activation, autophagy, and apoptosis-associated proteins in pulmonary artery tissue validated the results in PHAECs. Conclusions: These findings suggested that reduced autophagy, increased oxidative stress, increased platelet activation, and increased inflammation were involved in CTEPH-induced HPAEC dysfunction and the development of PH, while Resveratrol could improve PAEC dysfunction and PH.
  • FOXP3 variants are independently associated with transforming growth factor B1 plasma levels in female patients with inflammatory bowel disease Original Articles

    Inoue, Cláudia Junko; Flauzino, Tamires; Goncalves, Beatriz Piantoni; Paula, Jaqueline Costa Castardo de; Galvão, Talita Cristina; Miyazaki, Paula Kikuchi; Alcantara, Camila Cataldi de; Westmore, Lucilene Rosa e Silva; Lozovoy, Marcell Alysson Batisti; Reiche, Edna Maria Vissoci; Simão, Andréa Name Colado

    Resumo em Inglês:

    Abstract Objective: The aim of this study was to evaluate the association of -924 G>A (rs2232365) and -3279 C>A (rs3761548) FOXP3 variants with IBD susceptibility, clinical and endoscopic activity, and IL-10 and TGF-β1 plasma levels. Method: The study included 110 IBD female patients, 60 with Ulcerative Colitis (UC) and 50 with Crohn’s Disease (CD), and 154 female controls. FOXP3 variants were determined with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Plasma levels of IL-10 and TGF-β1 were determined using immuno-fluorimetric assay. Results: AA genotype of rs2232365 and rs3761548 was associated with CD (OR = 3.147, 95% CI 1.015-9.758, p = 0.047) and UC (OR = 3.221, 95% CI 1.050-9.876, p = 0.041) susceptibility, respectively. However, were not associated with TGF-β1 and IL-10 levels, and endoscopic/clinical activity disease. GAGA haplotype was associated with IBD (OR = 4.003, 95% CI 1.100–14.56, p = 0.035) and UC susceptibility (OR = 6.107, 95% CI 1.609–23.18, p = 0.008). In addition, IBD patients with the GAGA haplotype had lower TGF-β1 levels (p = 0.041). Moreover, G/C haplotype (dominant model) had a protective effect of 60% in CD susceptibility and lower Endoscopic Severity Index. Conclusions: These results suggest that FOXP3 variants could exert a role in the Treg, which could be one of the factors involved in the susceptibility and pathogenesis of IBD.
  • Circular RNA hsa_circ_0000317 inhibits non-small cell lung cancer progression through regulating microRNA-494-3p/phosphatase and tensin homolog deleted on chromosome 10 axis Original Articles

    Xia, Shihui; Zhang, Zengwang

    Resumo em Inglês:

    Abstract Background: Circular RNA (circRNA), a group of non-coding RNA, is pivotal in the progression of various cancers, including Non-Small Cell Lung Cancer (NSCLC). Some circRNAs have been reported to be implicated in the progression of NSCLC, however, the function and molecular mechanism of hsa_circ_0000317 (circ_0000317) in NSCLC have not been fully understood. Methods: The significantly differentially expressed circRNA in NSCLC tissues, circ_0000317, was screened out by microarray. Circ_0000317, microRNA(miR)-494-3p and Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) expressions in NSCLC tissues were respectively probed by quantitative real-time polymerase chain reaction and western blot assay. MTT and Transwell assays were adopted to examine the growth, migration, and invasion of NSCLC cells. Bioinformatics, luciferase reporter gene assay, RNA immunoprecipitation, and RNA pull-down assay were conducted to probe the relationships among circ_0000317, miR-494-3p, and PTEN. Results: Circ_0000317 expression level was reduced in NSCLC tissues and cell lines. Circ_0000317 expression in NSCLC patients was associated with TNM stage and lymphatic metastasis. Circ_0000317 overexpression restrained the proliferation, migration, and invasion of NSCLC cells, but co-transfection of miR-494-3p mimics partially reversed this effect. In addition, circ_0000317, was identified as a competitive endogenous RNA, which could sponge miR-494-3p to increase PTEN expression and activate PI3K/AKT pathway. Conclusion: Circ_0000317, inhibits NSCLC progression via modulating miR-494-3p/PTEN/PI3K/AKT pathway.
  • Risk factors of transplant renal artery stenosis in kidney transplant recipients Original Articles

    Kanhouche, Gabriel; Santos, Gustavo Rocha Feitosa; Orellana, Henry Campos; Galhardo, Attilio; Faccinetto, Ana Carolina Buso; Barteczko, Manoela Linhares Machado; Carvalho, Luiz Sérgio F. de; Taddeo, Julia Bernardi; Foresto, Renato Demarchi; Moises, Valdir Ambrósio; Tedesco-Silva, Helio; Pestana, José Medina; Barbosa, Adriano Henrique Pereira

    Resumo em Inglês:

    Abstract Background: Transplant Renal Artery Stenosis (TRAS) is a recognized vascular complication after kidney transplantation. The overall risk predictors of TRAS are poorly understood. Methods: Retrospective analysis of patients with suspected TRAS (Doppler ultrasound PSV > 200 cm/s) who underwent angiographic study in a single center between 2007 and 2014. All patients with stenosis > 50% were considered with TRAS. Stenosis restricted in the body of the artery was also analyzed in a subgroup. Results: 274 patients were submitted to a renal angiography and 166 confirmed TRAS. TRAS group featured an older population (46.3 ± 11.0 vs. 40.9 ±14.2 years; p = 0.001), more frequent hypertensive nephropathy (30.1% vs. 15.7%; p = 0.01), higher incidence of Delayed Graft Function (DGF) (52.0% vs. 25.6%; p < 0.001) and longer Cold Ischemia Time (CIT) (21.5 ± 10.6 vs. 15.7 ± 12.9h; p < 0.001). In multivariable analyses, DGF (OR = 3.31; 95% CI 1.78-6.30; p < 0.0001) was independent risk factors for TRAS. DM and CIT showed a tendency towards TRAS. The compound discriminatory capacity of the multivariable model (AUC = 0.775; 95% CI 0.718-0.831) is significantly higher than systolic blood pressure and creatinine alone (AUC = 0.62; 95% CI 0.558-0.661). In body artery stenosis subgroup, DGF (OR = 1.86; 95% CI 1.04-3.36; p = 0.03) and Diabetes Mellitus (DM) (OR = 2.44; 95% CI 1.31-4.60; p = 0.005) were independent risk factors for TRAS. Conclusion: In our transplant population, DGF increased more than 3-fold the risk of TRAS. In the subgroup analysis, both DGF and DM increases the risk of body artery stenosis. The addition of other factors to hypertension and renal dysfunction may increase diagnostic accuracy.
  • Two decades of liver resection with a multidisciplinary approach in a single institution: What has changed? Analysis of 1409 cases Original Articles

    Herman, Paulo; Fonseca, Gilton Marques; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirola; Makdissi, Fabio Ferrari; Jeismann, Vagner Birk; Carrilho, Flair José; D’Albuquerque, Luiz Augusto Carneiro; Nahas, Sergio Carlos

    Resumo em Inglês:

    Abstract Objectives: To evaluate results of patients undergoing liver resection in a single center over the past two decades with a particular look at Colorectal Liver Metastasis (CRLM) and Hepatocellular Carcinoma (HCC). Method: Patients were divided into two eras, from 2000 to 2010 (Era 1) and 2011 to 2020 (Era 2). The most frequent diagnosis was CRLM and HCC, with 738 (52.4%) and 227 (16.1%) cases respectively. An evaluation of all liver resection cases and a subgroup analysis of both CRLM and HCC were performed. Preoperative and per operative variables and long-term outcomes were evaluated. Results: 1409 liver resections were performed. In Era 2 the authors observed higher BMI, more: minimally invasive surgeries, Pringle maneuvers, and minor liver resections; and less transfusion, less ICU necessity, and shorter length of hospital stay. Severe complications were observed in 14.7% of patients, and 90-day mortality was 4.2%. Morbidity and mortality between eras were not different. From 738 CRLM resections, in Era 2 there were significantly more patients submitted to neoadjuvant chemotherapy, bilateral metastases, and smaller sizes with significantly less transfusion, the necessity of ICU, and shorter length of hospital stay. More pedicle clamping, minimally invasive surgeries, and minor resections were also observed. From 227 HCC resections, in Era 2 significantly more minimally invasive surgeries, fewer transfusions, less necessity of ICU, and shorter length of hospital stay were observed. OS was not different between eras for CRLM and HCC. Conclusions: Surgical resection in a multidisciplinary environment remains the cornerstone for the curative treatment of primary and metastatic liver tumors.
  • Micro ribonucleic acid-448 regulates zinc finger e-box binding homeobox 1 to inhibit the growth of breast cancer cells and increase their sensitivity to chemotherapy Original Articles

    Zhou, Yizhou; Sun, Li; Zhang, Yangmei; Chen, Kai

    Resumo em Inglês:

    Abstract Objective: This study aimed to investigate the effect of Zinc Finger E-box Binding Homeobox 1 (ZEB1) regulation by Micro Ribonucleic acid (miR)-448 on Breast Cancer (BC) cells and their sensitivity to chemotherapy. Methods: miR-448 and ZEB1 mRNA levels in BC and normal tissues were detected by qPCR, and ZEB1 protein was detected by Western Blotting (WB). The correlation between miR-448 and tumor metastasis, clinical staging, and ZEB1 expression was analyzed. MCF-7 cells were transfected or co-transfected with the miR-448 mimic, oe-ZEB1, or their negative controls. Changes in miR-448 and ZEB1 expression were detected by qPCR and WB. Cell proliferation was determined by CCK-8 assays, invasion changes were analyzed by Transwell assays, and apoptosis was detected by flow cytometry. Results: miR-448 expression in BC tissues was lower than that in normal tissues, while ZEB1 expression was increased in the former. ZEB1 expression was lower in BC patients with lymph node metastasis than in those without. In patients with clinical stage I-III BC, miR-448 expression decreased with an increase in tumor stage, which was negatively correlated with ZEB1 expression. Upregulation of miR-448 expression can suppress MCF-7 cell proliferation and invasion and promote apoptosis. Upregulation of ZEB1 expression in cells overexpressing miR-448 can partially reverse the inhibition of BC cell growth induced by miR-448. miR-448 can enhance the sensitivity of cells toward paclitaxel and 5-fluorouracil. Conclusions: miR-448 suppresses cell proliferation and invasion and promotes apoptosis by targeting ZEB1. Moreover, it can increase the sensitivity of cells toward paclitaxel and 5-fluorouracil.
  • Clinical significance of circulating tumor cells in predicating the outcomes of patients with colorectal cancer Original Articles

    Chen, Kehe; Chen, Zhenxiang; Ou, Mei; Wang, Junping; Huang, Xiao; Wu, Yingying; Zhong, Wenhe; Yang, Jiao; Huang, Jinging; Huang, Min; Pan, Deng

    Resumo em Inglês:

    Abstract Background: Relapse and metastasis of patients with Colorectal Cancer (CRC) is the major obstacle to the long-term life of patients. Its mechanisms remain defined. Methods: A total of 48 CRC patients were enrolled and 68 samples were obtained from the peripheral blood of patients before or after treatments in this study. Twenty non-cancer patients were also detected as a negative control. Circulating Tumor Cells (CTCs), including Epithelial CTCs (eCTCs), Mesenchymal (MCTCs), and epithelial/ mesenchymal mixed phenotypes (mixed CTCs), were identified by CanPatrolTM CTC enrichment and RNA in situ hybridization. The relationship between CTCs number and Progression-Free Survival (PFS) or Overall Survival (OS) was evaluated. Results: Thirty-four of 48 patients (70.8%) were found to have positive CTCs. Total CTCs and MCTCs in the post-treatment had a significant correlation PFS and OS. When total CTCs or MCTCs in 5 mL blood of patients were more than 6 CTCs or 5 MCTCs, PFS of the patients was significantly shorter (p < 0.05) than that in patients with less than 6 CTCs or 5 MCTCs. The patients with > 5 CTCs count changes were found to exhibit poor PFS and OS rates (p < 0.05). Conclusion: Total CTCs and MCTCs number detection in patients with colorectal cancer was very useful biomarker for predicting the prognosis of patients. Higher CTCs or MCTCs had poorer PFS and OS rates.
  • Effect of Beclin-1 gene silencing on autophagy and apoptosis of the prostatic hyperplasia epithelial cells Original Articles

    Liu, Rongfu; Zhang, Song; Wan, Rui; Deng, Jiang; Fang, Wei

    Resumo em Inglês:

    Abstract Objectives: This study aims to explore the effect of silencing Beclin-1 gene on autophagy and apoptosis of Benign Prostatic Hyperplasia (BPH) (BPH-1) cells under the condition of Androgen Deprivation (AD) and Autophagy Inhibition (AI). Methods: Control group (BPH-1 group), empty carrier group (sh-RNA-BPH-1 group) and Beclin-1 silenced group (sh-Beclin1-BPH-1 group) were set. The Beclin-1 gene silencing efficiency was detected by RT-PCR and Western blot. Autophagic flux was monitored by GFP-LC3 cleavage assay and cell apoptosis was analyzed by flow cytometry. The protein expression levels of LC3, Caspase-3, PARP-1, Bcl-2, and Bax were detected by Western blot. Results: The transfection of sh-Beclin-1 obviously down-regulated the expression of Beclin-1 at both mRNA and protein levels. Under the conditions of AD and AI, silencing of Beclin-1 restrained the autophagy of BPH-1 cells, as evidenced by a decreased number of autophagosomes and down-regulation of LC3-II protein (p < 0.001). The results of flow cytometry showed that the apoptotic rate of sh-Beclin-1 group was elevated significantly compared to the other two groups (p < 0.01). Western blot results showed that silencing of Beclin-1 promoted 89 kd fragmentation of PARP-1 (p < 0.001) and Caspase-3 activation (p < 0.01). Moreover, silencing of Beclin-1 resulted in declined Bcl-2 and augmented Bax protein expression in BPH-1 cells (p < 0.01), which ultimately led to a decreased Bcl-2/Bax ratio. Conclusions: The results indicated that the silencing of Beclin-1 gene hampered autophagy while activating apoptosis in BPH-1 cells. Thus, Beclin-1 may participate in an antagonistic relationship between autophagy and apoptosis in BPH.
  • Reference percentiles for bioimpedance body composition parameters of healthy individuals: A cross-sectional study Original Articles

    Amaral, Marina Azambuja; Mundstock, Eduardo; Scarpatto, Camila H.; Cañon-Montañez, Wilson; Mattiello, Rita

    Resumo em Inglês:

    Abstract Objectives: The aim of this study was to estimate the percentage distribution of body composition parameters for healthy people at different ages from the assessment of electrical bioimpedance. Methods: A cross-sectional study of healthy Brazilian aged 5 years and older. Were evaluated: total body fat; percent body fat; fat-free mass; percent lean mass; fat mass index; and fat-free mass index. Results: Of 1240 participants, with a median age of 27.0 years, 52.5% were female, and 73.7% were Caucasian. Most of the body composition variables were associated with age. The fat-free mass increased from youth to adult and decreased in the elderly in both sexes, with higher values in males than in females. In males, the percentage of lean mass has higher values in adolescence compared to childhood, and in adults compared to the elderly, when analyzed from the 50th percentile. In women, fat-free mass compared to adulthood, values were higher in childhood and lower in older ages. Conclusions: The study is the first to describe the Brazilian reference values for most clinical parameters of bioimpedance in percentiles stratified by different life cycles and sex. These findings can be very useful in clinical practice for health promotion and monitoring the nutritional status of the individual.
  • Surfactant Protein (SP) induces preterm birth by promoting oxidative stress via upregulating Storkhead-Box Protein 1 Original Articles

    Li, Xiafang; Zhang, Chunnian

    Resumo em Inglês:

    Abstract Preterm birth is the leading cause of infant mortality. The mechanisms that instigate preterm birth remain elusive and this makes it difficult to predict or prevent preterm birth. In this study, the authors found that SP-A induced pathological damage to the placenta and promoted preterm birth. Through mechanism, SP-A promoted the expression of STOX1 which further promoted the oxidative stress in the placenta by inhibiting the activities of a series of antioxidant enzymes including SOD, CAT and GSH-Px. SP-A also induced dysregulation of arginine metabolism by inhibiting NOS2 and ARG2. Overexpression of STOX1 aggravated SP-A induced oxidative stress, pathological damage, and preterm birth, whereas knockdown of STOX1 alleviated SP-A induced oxidative stress, pathological damage and preterm birth. The present study uncovers that SP-A induces preterm birth by promoting oxidative stress via upregulating STOX1, which provides new targets for the prediction and prevention of preterm birth.
  • Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription Original Articles

    Min, Jie; Ma, Jiaxing; Wang, Qi; Yu, Dexin

    Resumo em Inglês:

    Abstract Objective: Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. Method: The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. Results: SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. Conclusion: Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.
  • Hemodynamic depression after carotid surgery: Incidence, risk factors and outcomes Original Articles

    Bogniotti, Lauro A.C.; Teivelis, Marcelo P.; Cardozo, Francisco A.M.; Caramelli, Bruno; Wolosker, Nelson; Puech-Leão, Pedro; Luccia, Nelson De; Calderaro, Daniela

    Resumo em Inglês:

    Abstract Introduction: Hemodynamic Depression (HD) characterized by hypotension and bradycardia is a complication of carotid surgery due to direct autonomic stimulation in the carotid sinus. The authors believe the incidence of HD is high and possibly related to major cardiac complications. Methods: Analysis of patient records during admissions for carotid surgery between January 2014 and December 2018 in two hospitals. HD was defined as bradycardia or hypotension in the first 24 postoperative hours. Bradycardia was defined as heart rate < 50bpm; hypotension as systolic blood pressure < 90 mmHg, continuous use of vasopressors, or a drop in SBP > 20% compared to preoperative values. Myocardial infarction, stroke, and cardiovascular death were defined as adverse events. Results: Overall, 237 carotid surgeries (178 endarterectomies, 59 angioplasties) were studied, and the global incidence of HD was 54.4% (hypotension in 50.2%, bradycardia in 11.0%, and hypotension and bradycardia in 6.8%). The independent predictors of HD were asymptomatic carotid stenosis (OR = 1.824; 95% CI 1.014 −3.280; p = 0.045), endovascular surgery (OR = 3.319; 95% CI 1.675−6.576; p = 0.001) and intraoperative hypotension or bradycardia (OR = 2.144; 95% CI 1.222−3.762; p = 0.008). Hypotension requiring continuous vasopressor infusion was the only factor independently associated with adverse cardiovascular events (OR = 5.504; 95% CI 1.729-17.529; p = 0.004). Discussion/conclusion: Incidence of Hemodynamic Depression after carotid surgery is high and independently associated with surgical technique, symptomatic repercussion of the carotid stenosis, and intraoperative hypotension or bradycardia. Hypotension requiring the continuous infusion of vasopressors was independently associated with the occurrence of MACE.
  • Is 12 months enough to reach function after athletes’ ACL reconstruction: a prospective longitudinal study Original Articles

    Felix, Ellen Cristina Rodrigues; Alonso, Angelica Castilho; Brech, Guilherme Carlos; Fernandes, Tiago Lazzaretti; Almeida, Adriano Marques de; Luna, Natalia Mariana Silva; Soares-Junior, Jose Maria; Baracat, Edmund Chada; Hernandez, Arnaldo José; Greve, Julia Maria D’Andrea

    Resumo em Inglês:

    Abstract Context: Anterior Cruciate Ligament (ACL) injury is disabling in several sports because it causes knee instability and functional deficit. Usually, surgical treatments produce the best functional outcomes, however, sometimes they are not always able to fully restore stability and function. Objective: The objective of this study was to evaluate postural balance, muscle strength, and functional performance of young athletes with an ACL injury before and after ACL reconstruction. Design: This was a longitudinal observational prospective study. Method: 74 athletes, 60 men, and 14 women, aged between 16 and 45, divided into two groups: the Group-Lesion of ACL with 34 athletes (24.1 years) and the Group-Control with 40 athletes without ACL lesion (27.7 years old). All volunteers performed posturography, isokinetic dynamometry, and the Hop-Test. The ACL-Group was evaluated before and 12 months after the reconstruction and the control group was evaluated once. Results: The Postoperative ACL Group presented greater limb symmetry, 0.96 (± 0.12), than the preoperative ACL Group, 0.87 (± 0.17), p < 0.01 in the Hop-Test. In the posturography, the displacement area was smaller in the postoperative ACL Group, 19.85 (± 5.74), compared to the preoperative ACL Group, 24.20 (± 8.97), p < 0.01. In isokinetic dynamometry the torque peak was greater in the postoperative ACL Group, 0.91 (± 0.14), than in the preoperative ACL Group, 0.74 (± 0.15), p < 0.01. Conclusion: The functional outcomes increased in ACL reconstruction athletes after 12 months, but not at the same level as in the Control Group. The result indicates an incomplete functional recovery, adaptive changes in postural control after injury, reconstruction, and return to sport.
  • Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis Original Articles

    Prata, Thamiris Vaz Gago; Manchiero, Caroline; Dantas, Bianca Peixoto; Nunes, Arielle Karen da Silva; Tengan, Fátima Mitiko; Magri, Mariana Cavalheiro

    Resumo em Inglês:

    Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.
  • The etiologies of post-stroke depression: Different between lacunar stroke and non-lacunar stroke Original Articles

    Wang, Ke-Wu; Xu, Yang-Miao; Lou, Chao-Bin; Huang, Jing; Feng, Chao

    Resumo em Inglês:

    Abstract Objectives: Depression is common after both lacunar stroke and non-lacunar stroke and might be associated with lesion locations as proven by some studies. This study aimed to identify whether lesion location was critical for depression after both lacunar and non-lacunar strokes. Methods: A cohort of ischemic stroke patients was assigned to either a lacunar stroke group or a non-lacunar stroke group after a brain MRI scan. Neurological deficits and treatment response was evaluated during hospitalization. The occurrence of depression was evaluated 3 months later. Logistic regressions were used to identify the independent risk factors for depression after lacunar and non-lacunar stroke respectively. Results: 83 of 246 patients with lacunar stroke and 71 of 185 patients with non-lacunar stroke developed depression. Infarctions in the frontal cortex, severe neurological deficits, and a high degree of handicap were identified as the independent risk factors for depression after non-lacunar stroke, while lesion location was not associated with depression after lacunar stroke. Conclusion: The main determinants for depression after lacunar and non-lacunar stroke were different. Lesion location was critical only for depression after non-lacunar stroke.
  • Hepatocellular carcinoma (HCC) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD): screening, treatment and survival analysis in a Brazilian series Original Articles

    Alencar, Regiane Saraiva de Souza Melo; Oliveira, Claudia P.; Chagas, Aline Lopes; Fonseca, Leonardo Gomes da; Maccali, Claudia; Saud, Lisa Rodrigues da Cunha; Xerfan, Mariana Pinheiro; Stefano, Jose Tadeu; Herman, Paulo; D'Albuquerque, Luiz Augusto Carneiro; Alves, Venâncio Avancini Ferreira; Carrilho, Flair Jose

    Resumo em Inglês:

    Abstract Objective: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. Methods: This was a cross-sectional study at the Instituto do Cancer do Estado de São Paulo, at the Faculdade de Medicina da Universidade de São Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May 2010 to May 2019, were included. Results: A total of 131 patients were included. Risk factors for NAFLD were present in 94.7% of the patients. Only 29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in 84.7% of patients. Cumulative survival at the end of the first year was 72%, second-year 52%, and fifth-year 32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p < 0.001, and the size of the largest nodule > 42 mm, p = 0.039. Conclusions: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29% had screening), BCLC stages C‒D and the size of the largest nodule larger than 42 mm were identified as independent factors of worse prognosis.
  • Risk factors related to pleural empyema after talc slurry pleurodesis Original Articles

    D'Ambrosio, Paula Duarte; Araujo, Pedro Henrique Xavier Nabuco de; Rocha Junior, Eserval; Razuk Filho, Mauro; Pego-Fernandes, Paulo Manuel; Terra, Ricardo Mingarini

    Resumo em Inglês:

    Abstract Objective: Empyema is a complication of talc-pleurodesis that may lead to further surgical intervention and death. Therefore, the present study’s objective was to identify the risk factors for the development of post-pleurodesis empyema after talc slurry pleurodesis in order to better select patients for this procedure and minimize its morbidity. Methods: Patients with malignant pleural effusion who underwent talc slurry pleurodesis at the present institution from January 2018 to January 2020 were retrospectively analyzed. Post-pleurodesis empyema was defined as pleural infection up to 30 days after pleurodesis. Using Cox regression analysis, significant prognostic factors for the development of empyema were examined. Results: Of the 86 patients identified for inclusion in the study, 62 were women (72%). Their mean age was 56.3±12.6 years. The median pleural drainage time was 9 days, and 20 patients (23.3%) developed empyema. In the univariate analysis, both drainage time (p = 0.038) and the use of antibiotics prior to pleurodesis (p < 0.001) were risk factors for pleural empyema. Multivariate analysis also identified the use of antibiotics as an independent risk factor (Odds Ratio [OR] 9.81; 95% Confidence Interval [95% CI] 2.87–33.54). Although the pulmonary expansion was not associated with empyema in the multivariate analysis, patients with less than 50% pulmonary expansion had a 4.5-times increased risk of empyema (95% CI 0.90-22.86; p = 0.067), and patients with 50–70% pulmonary expansion had a 3.8-times increased risk of empyema (95% CI 0.98–15; p = 0.053) after pleurodesis. Conclusion: The study suggests that antibiotic therapy prior to talc slurry pleurodesis may increase the risk of developing empyema. Furthermore, pleurodesis should be considered with caution in patients with long-duration chest tube placement and incomplete lung expansion.
  • Evaluation of breast stiffness pathology based on breast compression during mammography: Proposal for novel breast stiffness scale classification Original Articles

    Prokop, Jiří; Maršálek, Pavel; Sengul, Ilker; Pelikán, Anton; Janoutová, Jana; Horyl, Petr; Roman, Jan; Sengul, Demet; Soares Junior, José Maria

    Resumo em Inglês:

    Abstract Breast cancer is diagnosed through a patient’s Breast Self-Examination (BSE), Clinical Breast Examination (CBE), or para-clinical methods. False negativity of PCM in breast cancer diagnostics leads to a persisting problem associated with breast tumors diagnosed only in advanced stages. As the tumor volume/size at which it becomes invasive is not clear, BSE and CBE play an exceedingly important role in the early diagnosis of breast cancer. The quality and effectiveness of BSE and CBE depend on several factors, among which breast stiffness is the most important one. In this study, the authors present four methods for evaluating breast stiffness pathology during mammography examination based on the outputs obtained during the breast compression process, id est, without exposing the patient to X-Ray radiation. Based on the subjective assessment of breast stiffness by experienced medical examiners, a novel breast stiffness classification was designed, and the best method of its objective measurement was calibrated to fit the scale. Hence, this study provides an objective tool for the identification of patients who, being unable to perform valid BSE, could benefit from an increased frequency of mammography screening. Dum vivimus servimus.
  • Clinical relevance of miR-423-5p levels in chronic obstructive pulmonary disease patients Original Articles

    Zhang, Xin; Shi, Qing; Xiong, Lu; Shi, Shiye; Li, Yong; Wang, Yanhuan; Zhang, Mingchuan

    Resumo em Inglês:

    Abstract Objective: This study aimed to examine changes in miRNAs expression profile of COPD patients. Methods: Thirty-six COPD patients as well as thirty-three healthy volunteers were recruited. Total RNAs were collected from the plasma of each participant. The differentially expressed miRNAs in COPD were screened from the GEO database. RT-qPCR was carried out to detect miRNA expression. Results: In total, 9 out of 55 miRNAs were expressed differentially in COPD patients. Confirmed by RT-qPCR validation, 6 miRNAs increased while 3 miRNAs decreased. Further analysis of miR-423-5p, which has not been reported in COPD, showed that AUC for the diagnosis of COPD was 0.9651, and miR-423-5p levels was inversely correlated with the duration of smoking. Conclusion: The present study demonstrates that miR-423-5p is a potential marker for identifying COPD patients.
  • LHX1 as a potential biomarker regulates EMT induction and cellular behaviors in uterine corpus endometrial carcinoma Original Articles

    Tian, Ye; Wen, Fang; Wang, Shuo; Lv, Na

    Resumo em Inglês:

    Abstract Objectives: To investigate the expression of LHX1 and its role as a biomarker in the diagnosis and prognosis of Uterine Corpus Endometrial Carcinoma (UCEC). Methods: The Cancer Genome Atlas (TCGA) database was used to detect the expression level of LHX1 in UCEC cells and tissues, and to find out the effect of LHX1 on prognosis. Co-expressed genes were then identified by Spearman correlation analysis, and the protein-protein interaction network was constructed using Cytoscape software. The R “clusterProfiler” package was used to conduct Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A series of in vitro experiments were performed to evaluate LHX1 expression and detect UCEC cell proliferation, invasion, and migration. Western blotting was used to determine the effect of LHX1 on expression levels of Epithelial-Mesenchymal Transition (EMT)-related proteins. Results: LHX1 was upregulated in UCEC tissues and correlated with poor overall survival and disease-specific survival outcomes. Functional enrichment analysis suggested that genes co-expressed with LHX1 were enriched in cell adhesion. The expression of LHX1 was positively correlated with the expression levels of genes related to EMT induction and invasion. LHX1 can enhance the proliferation, migration, and invasion activities of UCEC cells in vitro, and alter the expression levels of EMT-related proteins. Conclusion: LHX1 expression was highly upregulated in UCEC cells and tissues, which was correlated with the prognosis of patients with UCEC. LHX1 may regulate UCEC progression at least in part by modulating EMT induction.
  • The postoperative cognitive dysfunction induced by central inflammation with possible involvement of the gut-brain axis Original Articles

    Lin, Chuantao; Wang, Jing; Wang, Yuping; Chen, Chanjuan; Gao, Xiang

    Resumo em Inglês:

    Abstract Background: Postoperative cognitive dysfunction is widely recognized as severe postoperative central nervous dysfunction and has a significant impact on the ’patient’s physical and mental health. Methods: Postoperative models of tibial fracture in aged rats were established, including the control group, model group, CCL11 protein injection group, and saline injection group. Morris water maze test was used to detect the behavioral characteristics of rats. Enzyme-Linked Immunosorbent Assay was used or determine the content of CCL11 and CXCL10. Immunofluorescence staining was used to detect the distribution of CD14+CD163+macro-phages in colon tissues and CD11b+CCR3+microglia cells in hippocampal tissues. Western blot analyzed NOX1 and STAT3 expression in hippocampus tissues. Results: Water maze test results confirmed severe cognitive impairment in CCL11 rats. The content of CCL11 and CXCL10 in the CCL11 group was much higher than that of the model group. The distribution of macrophage and microglia cells in the CCL11 model group was greater than that in the model group and the saline group. The expression of NOX1 and STAT3 in the CCL11 group was higher compared with the model group. Conclusion: Abnormal macrophage function and excessive CCL11 secretion were observed in the rats with lower limb fractures after surgery. Postoperative central inflammation in rats with lower limb fracture induced postoperative cognitive dysfunction through the gut-brain axis molecular mechanism.
  • Isolated specific IgA against respiratory viruses, Influenza or SARS-CoV-2, present in the saliva of a fraction of healthy and asymptomatic volunteers Original Articles

    Zorgi, Nahiara Esteves; Meireles, Luciana R.; Oliveira, Danielle Bruna Leal; Araujo, Danielle Bastos; Durigon, Edson L.; Andrade Junior, Heitor Franco de

    Resumo em Inglês:

    Abstract Objectives: Defense against respiratory viruses depends on an immune response present in the mucosa, as saliva IgA secretes antibodies. During the pandemic, such as influenza or SARS-CoV-2, most infected patients are asymptomatic but retain specific antibodies post-infection. The authors evaluated IgG and IgA antibodies against SARS-CoV-2 and influenza in the saliva of asymptomatic volunteers, validated with controls or vaccinated individuals. Methods: The authors detected specific antibodies by validated conventional ELISA using natural SARS-CoV-2 antigens from infected Vero cells or capture-ELISA for influenza using natural antigens of the influenza vaccine. Results: Saliva from influenza-vaccinated individuals had more IgA than paired serum, contrary to the findings for specific IgG. In COVID-19-vaccinated samples, specific IgA in saliva increased after vaccination, but IgG levels were high after the first dose. In saliva from the asymptomatic population (226), anti-Influenza IgG was found in 57.5% (130) of samples, higher than IgA, found in 35% (79) of samples. IgA results were similar for SARS-CoV-2, with IgA present in 30% (68) of samples, while IgG was less present, in 44.2% (100) of samples. The proportion of influenza IgG responders was higher than that for SARS-CoV-2 IgG, but both populations presented similar proportions of IgA responders, possibly due to variable memory B cell survival. For both viruses, the authors found an important proportion (> 10%) of IgA+IgG- samples, suggesting the occurrence of humoral immunity directed to the mucosa. Conclusion: Specific antibodies for respiratory viruses in saliva are found in either infection or vaccination and are a convenient and sensitive diagnostic tool for host immune response.
  • Wound healing in weaning, adult, and old rats with provoked incisional hernias. A comparative study Original Articles

    Amaral, Raphael Nogueira do; Tannuri, Ana Cristina Aoun; Neri, Junia Marielle Teixeira Rodrigues; Reis, Hugo de Souza; Goncalves, Josiane Oliveira; Serafini, Suellen; Tannuri, Uenis

    Resumo em Inglês:

    Abstract Background: Incisional hernias are more frequent in adults than in children. It is hypothesized that a more efficient healing process in pediatric patients could explain this difference in incidence. Certain elements of healing such as neovascularization, degree of inflammation, percentage of mature and immature collagen, the proliferation of fibroblasts, and expression of certain genes could explain why healing in children is more efficient when compared to the adult and elderly populations. Materials and methods: Seventy-one rats of 3 different age groups (weaning, adult, and old) underwent surgery with 3 different incisions (vertical, oblique, and horizontal). During the procedure, the skin and abdominal wall of the animal were sectioned and only the skin was sutured to mimic incisional hernia in the animals. Four weeks after surgery, the rats were euthanized, their skin was removed, and the extent of scar tissue formed in the muscle opening was measured. In addition, samples of the scar tissue were collected for histological, immunohistochemical, and molecular analyzes. Nine rats served as controls. Results: Shorter-length hernias were formed in weaning rats when compared to old ones when the surgical incision was horizontal (p = 0.03). There was a greater proliferation of fibroblasts in rats in the younger age groups, regardless of the type of incision. The Lox gene was more expressed in weaning rats with vertical and oblique incisions. Conclusions: These differences could explain the better healing and lower incidence of hernias in the pediatric population, although this aspect requires further studies.
  • Relationship between lipoprotein (a) and subclinical carotid atherosclerosis in asymptomatic individuals Original Articles

    França, Victor; Gomes, Érica Ivana Lázaro; Campos, Edite Vieira Silva de; Zago, Vanessa Helena de Souza; Nunes, Valéria Sutti; Faria, Eliana Cotta de

    Resumo em Inglês:

    Abstract Background: This study aimed to evaluate the associations between Lipoprotein (a) ‒ Lp(a) levels and carotid Intima-Media Thickness (cIMT) and with carotid plaques in healthy subjects because of previous contradictory data. Methods: A total of 317 healthy normolipidemic subjects (20‒77 years old) were selected. The cIMT and atherosclerotic plaques were determined by B-mode ultrasonography. Mann-Whitney tests were performed to compare the groups according to Lp(a) levels and to explore the associations between Lp(a), carotid plaques, and cIMT, logistic and linear regression analyses were performed. Results: Studied population (51% females, median age 43 years old) presented carotid plaques and cIMT ≥ 0.9 mm in 23% and 18% of the participants, respectively. The group with Lp(a) levels > 30 mg/dL presented significantly higher age and atherosclerotic plaques. Indeed, multivariate linear regression analysis showed a significant association between Lp(a), age, and race. On the other hand, logistic regression analysis demonstrated that the subjects with Lp(a) > 30 mg/dL have a significantly high risk of carotid plaques. Conclusion: The data from the present study indicate that Lp(a) levels above 30 mg/dL contribute to the development of carotid plaques even in apparently healthy participants.
  • COVID-19 post-vaccination in healthcare workers and vaccine effectiveness, Brazil, 2021 Original Articles

    Fernandes, Caio Medeiros; Dias, Shirley L.; Ferreira, Maira C.; Luna, Expedito J.A.

    Resumo em Inglês:

    Abstract Objects: This study aimed to describe COVID-19 cases in healthcare workers at a large tertiary hospital, after a vaccination campaign, to understand the individual characteristics, timeliness, symptomatology, and severity of the conditions. Methods: The COVID-19 reporting files from the hospital’s healthcare workers and their records in the vaccine registry were analyzed, regarding vaccination status, symptoms, sociodemographic characteristics, comorbidities, and outcomes. Vaccination descriptive analysis was carried out and the impact and effectiveness of vaccination in relation to symptomatic infection and hospitalization were estimated. Results: In a total of 696 PCR-confirmed COVID-19 patients, vaccination coverage for the 1st and 2nd dose was 92.8% and 85.5%. Patients with complete doses had a mean interval of 96.8 days between vaccination and the onset of symptoms. Of the 664 participants with available clinical data, 165 had at least 1 comorbidity. During the study, 12 patients were hospitalized, 58.3% with a complete vaccination schedule. Three of this group died. The effectiveness of vaccination for symptomatic cases and hospitalization was 22.1% and 69.0%, respectively. The impact of vaccination on symptomatic cases and hospitalization was 81.4% and 89.7%, respectively. Discussion: The majority of COVID-19 cases in the study were classified as mild. The impact of vaccination for confirmed cases was significant, both in reducing the incidence of symptomatic cases and hospitalizations. The presence of comorbidities in approximately ¼ of the patients increased the risk of these individuals. The mean time interval between diagnosis and the 2nd dose of vaccine was longer in the hospitalized group, reinforcing the protective decline over longer periods.
  • Seroconversion in asymptomatic COVID-19 pediatric patients with rheumatic diseases of one tertiary referral hospital Original Articles

    Simon, Juliana R.; Pereira, Maria F.B.; Marques, Heloisa H.; Elias, Adriana M.; Sakita, Neusa K.; Ferreira, Juliana C.O.A.; Precioso, Alexander Roberto; Grisi, Sandra J.F.E.; Ferrer, Ana Paula S.; Bain, Vera; Silva, Clovis A.; Campos, Lúcia M.A.

    Resumo em Inglês:

    Abstract Objectives: To evaluate seroconverted asymptomatic COVID-19 in pediatric Autoimmune Rheumatic Diseases (ARDs) patients and to identify the risk factors related to contagion. Methods: A cross-sectional study was conducted in March 2021, before vaccination of children and adolescents in Brazil, including 77 pediatric ARDs patients, followed at a tertiary hospital and 45 healthy controls, all of them without a previous diagnosis of COVID-19. Data was obtained by a questionnaire with demographic data, symptoms compatible with COVID-19 over the previous year, and contact with people with confirmed COVID-19. Patient’s medical records were reviewed to access data regarding disease and current medications. A qualitative immunochromatographic SARS-CoV-2 test was performed on all participants. Results: Patients and controls were similar in terms of female gender (70.1% vs. 57.8%, p = 0.173), age (14 vs. 13 years, p = 0.269) and SARS-CoV-2 positive serology (22% vs. 15.5%, p = 0.481). 80.5% of rheumatic patients were in use of immunosuppressive drugs: 27.3% of them used corticosteroids (33.3% in high doses), and 7.8% on immunobiologicals. No statistical differences were found between positive (n = 17) and negative serology (n = 60) patients regarding demographic/socioeconomic data, contact with people with confirmed COVID-19, use and number of immunosuppressive drugs, use and dose of corticosteroids, use of hydroxychloroquine and immunobiological drugs (p > 0.05). Conclusions: Pediatric rheumatic disease patients were infected at the same rate as healthy ones. Neither the underlying pathology nor its immunosuppressive treatment seemed to interfere with contagion risk.
  • miRNA-223 expression in patient-derived eutopic and ectopic endometrial stromal cells and its effect on epithelial-to-mesenchymal transition in endometriosis Original Articles

    Xue, Yuan; Lin, Xueyan; Shi, Tingting; Tian, Yongjie

    Resumo em Inglês:

    Abstract Objective: This study was designed to evaluate the expression of microRNA-223 (miRNA-223) in patient-derived eutopic and ectopic endometrial stromal cells (SCs). Given the fact that miRNA-223 was previously shown to be upregulated in these cells and that this upregulation has been linked to epithelial-to-mesenchymal transition (EMT) during endometriosis, this study aimed to further explore the expression of miRNA-223, its effect in endometriosis, and the mechanisms underlying its effects. Methods: Endometrial tissue was collected from 26 patients with endometriosis and 14 patients with hysteromyoma (control group). Primary endometrial SCs were isolated and cultured from several endometrial samples and miRNA-223 expression was evaluated using qRT-PCR. Cells were then transfected with a miRNA-223 overexpression lentiviral vector (sh-miR-223 cells) or an empty control (sh-NC cells) and then used to monitor the effects of miRNA-223 on the expression of several EMT-associated proteins, including N-cadherin, vimentin, and Slug, using western blot. Cellular migration, invasion, and proliferation were then evaluated using a wound healing, Transwell, and CCK-8 assay, respectively. Flow cytometry was used to detect apoptosis. Results: There was a significant decrease in the expression of miRNA-223 in both eutopic and ectopic endometrial SCs (p < 0.05) whereas upregulation of miRNA-223 inhibited the expression of EMT-related molecules and reduced cell migration, invasion, and proliferation. High levels of miRNA-223 also promoted apoptosis. Conclusion: miRNA-223 expression decreased in endometrial SCs from endometriosis patients, which may facilitate the differential regulation of EMT during endometriosis. Clinical Trial registration number: SWYX2020-211.
  • Higher visceral adiposity index is associated with increased likelihood of abdominal aortic calcification Original Articles

    Qin, Zheng; Jiang, Luojia; Sun, Jiantong; Geng, Jiwen; Chen, Shanshan; Yang, Qinbo; Su, Baihai; Liao, Ruoxi

    Resumo em Inglês:

    Abstract Background: The negative effects of visceral adiposity accumulation on cardiovascular health have drawn much attention. However, the association between the Visceral Adiposity Index (VAI) and Abdominal Aortic Calcification (AAC) has never been reported before. The authors aimed to investigate the association between the VAI and AAC in US adults. Methods: Cross-sectional data were derived from the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) of participants with complete data of VAI and AAC scores. Weighted multivariable regression and logistic regression analysis were conducted to explore the independent relationship between VAI and AAC. Subgroup analysis and interaction tests were also performed. Results: A total of 2958 participants were enrolled and participants in the higher VAI tertile tended to have a higher mean AAC score and prevalence of severe AAC. In the fully adjusted model, a positive association between VAI and AAC score and severe AAC was observed (β = 0.04, 95% CI 0.01‒0.08; OR = 1.04, 95% CI 1.01‒1.07). Participants in the highest VAI tertile had a 0.41-unit higher AAC score (β = 0.41, 95% CI 0.08‒0.73) and a significantly 68% higher risk of severe AAC than those in the lowest VAI tertile (OR = 1.68, 95% CI 1.04‒2.71). Subgroup analysis and interaction tests indicated that there was no dependence for the association of VAI and AAC. Conclusion: Visceral adiposity accumulation evaluated by the VAI was associated with a higher AAC score and an increased likelihood of severe AAC.
  • Effects of oxytocin versus promestriene on genitourinary syndrome: a pilot, prospective, randomized, double-blind study Original Articles

    Santos, Liani Patricia Andrade; Bonduki, Claudio Emílio; Dardes, Rita de Cassia de Maio; Heinke, Thais; Patriarca, Marisa Teresinha

    Resumo em Inglês:

    Abstract Objectives: In this pilot, prospective, randomized, double-blind study, the authors compared the efficacy of oxytocin with promestriene in improving vaginal atrophy of Genitourinary Syndrome of Menopause (GSM). Methods: A total of 51 postmenopausal women with symptoms of GSM were evaluated. They were randomized into two groups: oxytocin (25 patients) and promestriene (26 patients) and were evaluated before and after 90 days of treatment; the evaluation was based on the domains of the Female Sexual Function Index (FSFI) (lubrication, satisfaction, and pain during sexual intercourse), clinical visual examination, and vaginal wall thickness. Results: After the use of the medications, both groups showed significant improvement in the three evaluated FSFI domains (p < 0.05) and there was no significant difference between the groups (p > 0.05). On clinical examination, the medications improved all the evaluated parameters but without statistical significance (p > 0.05). The evaluation of the thickness of the vaginal epithelium showed that both treatments led to increase in the vaginal epithelium (p < 0.05); however, the efficacy of promestriene was higher than that of oxytocin (p < 0.05). Conclusions: Both medications were effective, however, studies with larger samples and longer follow-ups are needed to confirm the clinical applicability.
  • Comparative effects of fractional radiofrequency and microneedling on the genitalia of postmenopausal women: Histological and clinical changes Original Articles

    Maia, Rafaella Rêgo; Sarmento, Ayane Cristine; Silva, Rodrigo Marcel Valentim da; Carreiro, Eneida de Morais; Farias, Stephany Luanna Queiroga; Soares, Ciro Dantas; Meyer, Patrícia Froes; Gonçalves, Ana Katherine

    Resumo em Inglês:

    Abstract Objectives: The authors aimed to evaluate clinical and histological changes induced by Fractional Radiofrequency (FRF) and microneedling in vulvar tissue. Methods: Thirty postmenopausal women were randomly divided into G1 (FRF) and G2 (microneedling) groups. Sub-ablative FRF was executed using disposable fractionated electrodes with an intensity of 8 mJ. Microneedling was performed using a derma roller system. The authors evaluated before and after treatment using the Vaginal Laxity Questionnaire (VLQ), EuroQol Five-Dimensional (EQ-5D) questionnaire, and the Blatt and Kupperman Menopausal Index (BKMI). Additionally, the authors performed biopsies of the labia majora for histological analysis pre- and post-treatment. Data were expressed as mean (± standard deviation). A paired t-test was used for intra-group comparison (pre- and post-treatment), with an independent t-test used to compare intergroup data (both pre- and post-treatment). Results: In the G1 group, the VLQ values showed differences compared to the pre-treatment values with the data obtained 60 days after the beginning of the sessions (p = 0.01). Similarly, the data changes of the G2 group proved to be significant (p = 0.001) across the same time interval. In comparing the groups, VLQ values were not different (p > 0.05). Regarding histological analysis, FRF demonstrated improvement concerning the number of fibroblasts, blood vessels, and fatty degeneration (p < 0.05) compared to the control. Additionally, FRF and microneedling samples showed higher type III collagen and vimentin expression in the immunohistochemical analysis (p < 0.05). Conclusions: The therapies were found to be effective in treating the flaccidity of the female external genitalia. Additionally, histological changes were observed after interventions suggesting collagen remodeling.
  • Central auditory processing in children after traumatic brain injury Original Articles

    Godoy, Carolina Calsolari Figueiredo de; Andrade, Adriana Neves de; Suriano, Italo; Matas, Carla Gentile; Gil, Daniela

    Resumo em Inglês:

    Abstract Introduction: Traumatic brain injury can impair the central auditory pathways and auditory cortex. Hence, individuals who suffered a traumatic brain injury may be at risk of central auditory processing disorders, which can be identified with behavioral tests that assess central auditory function. Objective: To characterize and compare the performance of children and adolescents with and without a history of traumatic brain injury in behavioral tests that assess central auditory processing. Method: The sample comprised 8- to 18-year-old individuals of both sexes who suffered moderate or severe closed traumatic brain injury 3 to 24 months before their participation in the study and whose hearing thresholds were normal. These individuals were matched for sex and age with other subjects without a history of traumatic brain injury and submitted to behavioral assessment of the central auditory processing with special tests to assess hearing skills (namely, auditory closure, figure-ground, and temporal processing), selected according to their chronological age and response-ability. Results: The study group performed statistically worse than the comparison group in auditory closure, figure-ground in verbal dichotic listening, and temporal ordering. The central auditory processing tests with abnormal results in the comparison group were different from those in the study group. Conclusion: Central auditory processing disorders were identified in all subjects of the study group, especially involving auditory closure and temporal processing skills, in comparison with subjects without a history of traumatic brain injury.
  • Melatonin protects against ovarian damage by inhibiting autophagy in granulosa cells in rats Original Articles

    Liu, Yan; Zhu, Xiaohe; Wu, Chunli; Lang, Yan; Zhao, Wenjie; Li, Yanmin

    Resumo em Inglês:

    Abstract Objectives: This study sought to further verify the protective mechanism of Melatonin (MT) against ovarian damage through animal model experiments and to lay a theoretical and experimental foundation for exploring new approaches for ovarian damage treatment. Method: The wet weight and ovarian index of rat ovaries were weighted, and the morphology of ovarian tissues and the number of follicles in the pathological sections of collected ovarian tissues were recorded. And the serum sex hormone levels, the key proteins of the autophagy pathway (PI3K, AKT, mTOR, LC3II, LC3I, and Agt5) in rat ovarian tissues, as well as the viability and mortality of ovarian granulosa cells in each group were measured by ELISA, western blotting, CCK8 kit and LDH kit, respectively. Results: The results showed that MT increased ovarian weight and improved the ovarian index in ovarian damage rats. Also, MT could improve autophagy-induced ovarian tissue injury, increase the number of primordial follicles, primary follicles, and sinus follicles, and decrease the number of atretic follicles. Furthermore, MT upregulated serum AMH, INH-B, and E2 levels downregulated serum FSH and LH levels in ovarian damage rats and activated the PI3K/AKT/mTOR signaling pathway. Besides, MT inhibited autophagic apoptosis of ovarian granulosa cells and repressed the expression of key proteins in the autophagic pathway and reduced the expression levels of Agt5 and LC3II/I. Conclusions: MT inhibits granulosa cell autophagy by activating the PI3K/Akt/mTOR signaling pathway, thereby exerting a protective effect against ovarian damage.
  • TRIM47 promotes ovarian cancer cell proliferation, migration, and invasion by activating STAT3 signaling Original Articles

    Wang, Xi; Fu, Yu; Xing, Yanyan

    Resumo em Inglês:

    HIGHLIGHTS Knockdown of TRIM47 suppressed proliferation of ovarian cancer cells. Knockdown of TRIM47 inhibited ovarian cancer cell migration and invasion. TRIM47 promoted ovarian cancer cell proliferation and invasion via STAT3 signaling.
  • The supplementation of L-carnitine in septic shock patients: Systematic review and meta-analysis Original Articles

    Guedes, Gabriel Voltani; Minicucci, Marcos Ferreira; Tanni, Suzana Erico

    Resumo em Inglês:

    HIGHLIGHTS The objective of this review was to evaluate the effect of L-carnitine compared to placebo or Usual Care (UC) on the mortality rate in hospitalized adult septic shock patients. Two Randomized Controlled Trials were selected for inclusion in this review There is low-quality evidence that L-carnitine has no significant effect on 28-day mortality of septic shock patients
  • The variability of isokinetic ankle strength is different in healthy older men and women Original Articles

    Bersotti, Felipe Marrese; Mochizuki, Luis; Brech, Guilherme Carlos; Soares, André Luiz de Seixas; Soares-Junior, Jose Maria; Baracat, Edmund Chada; Greve, Julia Maria D'Andrea; Alonso, Angelica Castilho

    Resumo em Inglês:

    HIGHLIGHTS Older men are stronger than older women. Higher torque variability in older men. Adaptation to the isokinetics evaluation. Different muscles need different numbers of sets. Different muscles need different numbers of trials.
  • Prevalence of oncogenic human papillomavirus in pregnant adolescents, association with colpocytological changes, risk factors and obstetric outcomes Original Articles

    de Souza, Henrique Diório; Waissman, Adriana Lippi; Diório, Giselle Rodrigues Mota; Peres, Stela Verzinhasse; Francisco, Rossana Pulcineli Vieira; Galletta, Marco Aurélio Knippel

    Resumo em Inglês:

    HIGHLIGHTS One out of every two pregnant adolescents (50.5%) followed in prenatal care were positive for high-risk HPV and about 1 in 6 pregnant women (17.5%) had an abnormal Pap smear. Positivity for oncogenic HPV was an important risk factor for colpocytological alterations, especially for Low-grade Squamous epithelial Lesion (LSIL), increasing the risk by nine times. Higher education, fewer lifetime partners, and profession of religion were associated with the diagnosis of oncogenic HPV in pregnancy.
  • The health facility as a risk factor for multidrug-resistant gram-negative bacteria in critically ill patients with COVID-19 Original Articles

    de Macedo, Viviane; dos Santos, Gabriela de Souza; da Silva, Rodolff Nunes; Couto, Caio Nogara de Menezes; Bastos, Camila; Viecelli, Eloize; Mateus, Marina do Nascimento; Graf, Maria Esther; Gonçalves, Raquel Bernardelli; da Silva, Márcia Aparecida; Bernardini, Patricia Dal Bem; Grando, Roberta Serra Pereira; Boaventura, Viviane Pavanelo; Pereira, Helki Simone Rodrigues; Levin, Anna S.

    Resumo em Inglês:

    HIGHLIGHTS Critically ill patients with COVID-19 can have secondary infections. Some of them are caused by Multidrug-Resistant (MDR) Gram-Negative Bacteria (GNB). To know the risk factors related to MDR-GNB is essential to analyze if it is possible to prevent them. Hospital of admission for patients with COVID-19 posed as high risk for MDR-GNB. This is a modifiable risk factor.
  • Targeted massively parallel sequencing panel to diagnose genetic endocrine disorders in a tertiary hospital Original Articles

    Narcizo, Amanda M.; Cardoso, Lais C.; Benedetti, Anna F.F.; Jorge, Alexander A.L.; Funari, Mariana F.A.; Braga, Barbara L.; Franca, Monica M.; Montenegro, Luciana R.; Lerario, Antonio M.; Nishi, Mirian Y.; Mendonca, Berenice B.

    Resumo em Inglês:

    HIGHLIGHTS The multigenic panel effectively diagnoses patients with endocrine diseases. It is the first panel to diagnose a broad spectrum of endocrine diseases using TMPS. This panel helps the visualization of molecular pathways behind endocrine conditions.
  • Monocyte-to-HDL ratio and non-HDL cholesterol were predictors of septic shock in newborns Original Articles

    Fonseca, Fernanda Andrade Macaferri da; Espósito, Aline Paulino; Silva, Maria Helena Baptista Nunes da; Nunes, Valéria Sutti; Cazita, Patricia Miralda; Ferreira, Guilherme Silva; Ceccon, Maria Esther Jurfest Rivero; Carvalho, Werther Brunow de; Carneiro-Sampaio, Magda; Palmeira, Patricia

    Resumo em Inglês:

    Abstract Background The association between lipoprotein levels and late-onset neonatal sepsis has shown controversial results. The aims are to assess lipid profile, cytokines, and Monocyte-to-HDL (M/H) ratio as diagnostic and prognostic markers for late-onset neonatal sepsis. Methods This prospective study included 49 septic neonates and 17 controls. Cholesterol (CT), Triglyceride (TG), Very-Low-Density (VLDLc), Low-Density (LDLc), and High-Density Lipoproteins (HDLc) were measured at admission (D0) and on days 3, 7 and 10 to evaluate septic shock outcomes. Cytokines and monocytes were evaluated by flow cytometry. Results Septic newborns showed higher IL-6 and IL-8 at D0 and CT levels on D7 and on D10, which also presented higher TG, VLDLc and non-HDL cholesterol concentrations than controls. The septic shock group (n = 22) revealed a higher number of male subjects, CRP, IL-6, IL-8 and IL-10 levels, while lower TG, HDLc, monocyte numbers and M/H ratio at admission compared to the non-shock group (n = 27). M/H ratio and non-HDL cholesterol on D0 were risk factors for septic shock (OR = 0.70, 0.49‒0.99; OR = 0.96, 0.92‒0.99, respectively). Decreasing levels from D0 to D3 of CT (OR = 0.96, 0.93‒0.99), VLDLc (OR = 0.91, 0.85‒0.98), and non-HDL cholesterol (OR = 0.92, 0.87‒0.98) were also predictors of septic shock. Conclusions Lower M/H ratios and non-HDL cholesterol at admission and decreasing levels of cholesterol, VLDLc and non-HDL cholesterol during a hospital stay are associated with the development of septic shock in newborns with late-onset neonatal sepsis.
  • MiR-135a-5p suppresses breast cancer cell proliferation, migration, and invasion by regulating BAG3 Original Articles

    Zhang, Hongxu; Wang, Minghui; Lang, Zhiqiang; Liu, Haiwang; Liu, Jianping; Ma, Lihui

    Resumo em Inglês:

    Abstract Background MicroRNAs (miRNAs) are involved in the progression of diverse human cancers. This work aimed to delve into how microRNA-135a-5p (miR-135a-5p) affects the biological behaviors of Breast Cancer (BC) cells. Methods Gene Expression Omnibus (GEO) datasets were used to analyze the expression differences of miR-135a-5p in cancer tissues of BC patients. Quantitative real-time PCR and western blot were conducted to detect miR-135a-5p and Bcl-2 Associated Athanogene (BAG3) expression levels in BC tissues and cells, respectively. The proliferation, migration, invasion, and cell cycle of BC cells were detected by cell counting kit-8 assay, BrdU assay, wound healing assay, transwell assay, and flow cytometry. The targeted relationship between miR-135a-5p and BAG3 mRNA 3′UTR predicted by bioinformatics was further testified by a dual-luciferase reporter gene assay. Pearson's correlation analysis was adopted to analyze the correlation between miR-135a-5p expression and BAG3 expression. The downstream pathways of BAG3 were analyzed by the LinkedOmics database. Results MiR-135a-5p was significantly down-regulated and BAG3 expression was significantly raised in BC tissues. MiR-135a-5p overexpression repressed the viability, migration and invasion of BC cells, and blocked cell cycle progression in G0/G1 phase while inhibiting miR-135a-5p worked oppositely. BAG3 was verified as a target of miR-135a-5p. Overexpression of BAG3 reversed the impacts of miR-135a-5p on the malignant biological behaviors of BC cells. The high expression of BAG3 was associated with the activation of the cell cycle, mTOR and TGF-β signaling pathways. Conclusion MiR-135a-5p regulates BAG3 to repress the growth, migration, invasion, and cell cycle progression of BC cells.
  • High expression of prolyl 4-hydroxylase subunit alpha-2 in lung adenocarcinoma indicates poor prognosis Original Articles

    Lu, Xiao-Hong; Sang, Die; Zhang, Yu-Rong; Yuan, Qing

    Resumo em Inglês:

    Abstract Objective To analyze the Prolyl 4-Hydroxylase subunit Alpha-2 (P4HA2) expression in Lung Adenocarcinoma (LAUD). Methods The authors assessed P4HA2 expression in the LUAD tumor ecosystem using single-cell analysis. The authors analyzed the relationship between P4HA2 expression and clinical features in LUAD and Brain Metastasis (BM) cases. The authors assessed the biological functions of P4HA2 using The Cancer Genome Atlas-LUAD dataset. Results P4HA2 was more highly expressed in fibroblasts than in epithelial cells in normal lung and lung adenocarcinoma tissues (p < 0.001). P4HA2 was more highly expressed in malignant epithelial cells than in fibroblasts in the BM tissue (p = 0.002). P4HA2 expression was significantly higher in female cases than in male cases (p = 0.049) and was related to lymph node metastasis (p = 0.019) and a higher TNM stage (p = 0.020). High P4HA2 expression indicated a poor prognosis and served as an independent prognostic risk factor in lung cancer. P4HA2 was mainly enriched in the extracellular matrix organization, NADH regeneration, and canonical glycolysis. P4HA2 expression was negatively correlated with naive B cells, T-cells, CD8, and activated natural killer cells, but positively correlated with CD4 memory-activated T cells, regulatory T-cells, resting dendritic cells, and dendritic cell activation. P4HA2 messenger RNA expression was correlated with programmed death-ligand 1 and cytotoxic T-lymphocyte-associated protein 4. Conclusion P4HA2 is highly expressed in LUAD tumor cells, especially for the BM subtype, and is a valuable prognostic indicator of LUAD. It may be involved in a biological activity of distant metastasis of LUAD tumor cells and serve as a potential treatment target.
  • Clinical and anatomical characteristics associated with obstructive sleep apnea severity in children Original Articles

    Bozzini, Maria Fernanda; Di Francesco, Renata C.; Soster, Letícia A.

    Resumo em Inglês:

    Abstract Purpose To determine the clinical and anatomical characteristics associated with obstructive sleep apnea severity in children with adenotonsillar hypertrophy. Methods The authors conducted a cross-sectional multidisciplinary survey and selected 58 Brazilian children (4‒9 years old) with adenotonsillar hypertrophy, parental complaints of snoring, mouth-breathing, and witnessed apnea episodes. The authors excluded children with known genetic, craniofacial, neurological, or psychiatric conditions. Children with a parafunctional habit or early dental loss and those receiving orthodontic treatment were not selected. All children underwent polysomnography, and three were excluded because they showed an apnea-hypopnea index lower than one or minimal oxygen saturation higher than 92%. The sample consisted of 55 children classified into mild (33 children) and moderate/severe (22 children) obstructive sleep apnea groups. Detailed clinical and anatomical evaluations were performed, and anthropometric, otorhinolaryngological, and orthodontic variables were analyzed. Sleep disorder symptoms were assessed using the Sleep Disturbance Scale for Children questionnaire. All children also underwent teleradiography exams and Rickett's and Jarabak's cephalometric analyses. Results The mild and moderate/severe obstructive sleep apnea groups showed no significant differences in clinical criteria. Facial depth angle, based on Ricketts cephalometric analysis, was significantly different between the groups (p= 0.010), but this measurement by itself does not express the child's growth pattern, as it is established by the arithmetic mean of the differences between the obtained angles and the normal values of five cephalometric measurements. Conclusions The clinical criteria and craniofacial characteristics evaluated did not influence the disease severity.
  • Diagnosis of parapneumonic pleural effusion with serum and pleural fluid Activin A Original Articles

    Zhou, Guanghui; Liu, Kan; Ji, Xiuhai; Fen, Yan; Gu, Yinjie; Ding, Hui

    Resumo em Inglês:

    Abstract Objective The aim is to evaluate the diagnostic value of Activin A levels in serum and pleural fluid on Parapneumonic Pleural Effusion (PPE). Methods The authors collected serum and pleural fluid from 86 PPE and 37 Non-PPE (NPPE) patients. Including Activin A, levels of biomarkers such as Lactate Dehydrogenase (LDH), Procalcitonin (PCT), and C-Reactive Protein (CRP) were measured. All factors were calculated for association with days after admission. The diagnostic potential of biomarkers on PPE was considered by Receiver Operating Characteristic (ROC) curve analysis. Results Levels of Activin A in serum and pleural fluid of PPE patients were significantly higher than those of the NPPE patients. Moreover, concentrations of Activin A in pleural fluid showed a more obvious relevant days after admission. ROC curve analysis found that Activin A in pleural fluid had AUCs of 0.899 with 93% sensitivity and 84% specificity for PPE diagnosis. Conclusion Activin A in pleural fluid correlated with disease severity could act to diagnose PPE.
  • Relevant proteins for the monitoring of engraftment phases after allogeneic hematopoietic stem cell transplantation Original Articles

    Souza, Milena Monteiro; Coutinho-Camillo, Cláudia Malheiros; de Paula, Fabiana Martins; de Paula, Fernanda; Bologna, Sheyla Batista; Lourenço, Silvia Vanessa

    Resumo em Inglês:

    Abstract Introduction Hematopoietic Stem Cell Transplant (HSCT) has been successfully used as standard therapy for hematological disorders. After conditioning therapy, patients undergoing allogeneic HSCT, present three different phases of engraftment: early pre-engraftment, early post-engraftment, and late engraftment. Severe complications are associated with morbidity, mortality, and malignancies in these phases, which include effects on the oral cavity. Objectives The changes in the salivary composition after HSCT may contribute to identifying relevant proteins that could map differences among the phases of diseases, driven for personalized diagnostics and therapy. Methods Unstimulated whole saliva was collected from patients submitted to HSCT. The samples were submitted to trypsin digestion for a Mass spectrometry analysis. MaxQuant processed the Data analysis, and the relevant expressed proteins were subjected to pathway and network analyses. Results Differences were observed in the most identified proteins, specifically in proteins involved with the regulation of body fluid levels and the mucosal immune response. The heatmap showed a list of proteins exclusively expressed during the different phases of HSCT: HBB, KNG1, HSPA, FGB, APOA1, PFN1, PRTN3, TMSB4X, YWHAZ, CAP1, ACTN1, CLU and ALDOA. Bioinformatics analysis implicated pathways involved in protein processing in the endoplasmic reticulum, complement and coagulation cascades, apoptosis signaling, and cholesterol metabolism. Conclusion The compositional changes in saliva reflected the three phases of HSCT and demonstrated the usefulness of proteomics and computational approaches as a revolutionary field in diagnostic methods.
  • Clinical characteristics and evolution of 71 neonates born to mothers with COVID-19 at a tertiary center in Brazil Original Articles

    Duarte, Bruna de Paula; Krebs, Vera Lucia Jornada; Calil, Valdenise Martins Laurindo Tuma; Carvalho, Werther Brunow de; Gibelli, Maria Augusta Bento Cicaroni; Francisco, Rossana Pulcineli Vieira

    Resumo em Inglês:

    Abstract Introduction Limited data are available on pregnant women with COVID-19 and their neonates. Objective This study aimed to describe clinical characteristics and evolution from birth to discharge of a retrospective cohort of 71 neonates, with one set of twins, born to women with COVID-19 diagnosed at the end of pregnancy. The authors included all newborns admitted into a neonatal unit of a tertiary hospital in Brazil, between March 2020 and March 2021, whose unvaccinated mothers had COVID-19 symptoms and RT-PCR (Real-Time Polymerase Chain Reaction) for SARS-CoV-2 positive within fourteen days prior to delivery. Newborns to mothers with COVID-19 symptoms and negative tests for SARS-CoV-2 were excluded. Results The main route of birth delivery was cesarean, corresponding to 60 pregnant women (84.5%). The foremost indications for cesarean were pregnant with critical disease (24.6%) and acute fetal distress (20.3%). The mean birth weight was 2452 g (865‒3870 g) and the mean gestational age was 345/7weeks (25‒40 weeks). There were 45 premature newborns (63.3%), of which 21 newborns (29.5%) were less than 32 weeks of gestational age. RT-PCR for SARS-CoV-2 on oropharyngeal swabs was positive in 2 newborns (2.8%) and negative in the other 69 newborns (97.2%). Most newborns (51.4%) needed respiratory support. Therapeutic interventions during hospitalization were inotropic drugs (9.9%), antibiotics (22.8%), parenteral nutrition (26.8%), and phototherapy (46.5%). Conclusion Maternal COVID-19 diagnosticated close to delivery has an impact on the first days of neonatal life.
  • Adolescents’ knowledge of HPV and sexually transmitted infections at public high schools in São Paulo: A cross-sectional study Original Articles

    Soares Junior, Jose Maria; de Oliveira, Hervillin Maria Creusa; Luquetti, Camilla Maganhin; Zuchelo, Lea Tami Suzuki; de Arruda Veiga, Eduardo Carvalho; Raimundo, Juliana Zangirolami; dos Santos Figueiredo, Francisco Winter; Alves, Mayara Souza; Sorpreso, Isabel Cristina Esposito; Baracat, Edmund Chada

    Resumo em Inglês:

    Abstract Purpose To assess the knowledge of students from public high schools in poor communities about HPV and Sexually Transmitted Infections and their attitude towards and prevention of such diseases. Patients and methods Cross-sectional study with adolescents from public schools of São Paulo - Brazil. Participants were selected for an interview by a randomization program. A questionnaire about knowledge, attitudes, and preventive practices regarding STIs, including HPV, according to sex was administered and answers were analyzed by the Poisson regression model with robust variance. Results Median age of the 269 participants was 16 years. The majority was of African descent (68.8%, n = 185), most (74%, n = 199) were religious and the vast majority (90.7%, n = 244) lived with their parents. The Poisson regression revealed statistically significant sex-related differences regarding the following questions: “Do you know how it is prevented?” (PR = 1.12 [1.03‒1.23], p = 0.007); “Have you ever been concerned with HPV?” (PR = 1.10 [1.02‒1.19], p = 0.011); “Have you ever sought health care due to concerns about HPV?” (PR = 1.09 [1.04‒1.14], p < 0.001); “Do you know what a Pap Smear is?” (PR = 1.24 [1.13‒1.36], p < 0.001); “Do you know what the cervix is?” (PR = 1.23 [1.13‒1.34], p < 0.001); “Do you know what cervical cancer is?” (PR = 1.13 [1.04‒1.22], p = 0.004). Conclusions The present results show that adolescents from public schools in poor communities in São Paulo City know little about HPV and cervical cancer. Male adolescents know less than female adolescents and are less concerned with health care.
  • Methylene Blue to Neonatal Septic Shock treatment in neonate pigs, Original Articles

    Gonçalves-Ferri, Walusa Assad; Albuquerque, Agnes Afrodite Sumarelli; de Castro, Renata Sayuri Ansai Pereira; Ferreira, Cristina Helena Faleiros; Oharomari Jr., Luis K.; Silva Lessa, Diego Fernando; Evora, Paulo Roberto Barbosa

    Resumo em Inglês:

    Abstract Objective The authors design an animal model of neonatal sepsis to analyze the treatment of neonatal septic shock with Methylene Blue (MB) in a swine model. Methods The study design included twenty male newborn pigs divided into four groups: 1) The control group; 2) The sepsis group (induced with lipopolysaccharide); 3) The MB group, and 4) The MB-treated sepsis group. Septic shock was defined as Blood Pressure (BP) dropping 20% below the baseline value. Continuous Blood Pressure (BP), Nitric Oxide (NO) levels, cyclic Guanosine Monophosphate (cGMP), malondialdehyde acid, base excess, lactate, arterial blood gases, hematocrit, and echocardiography were analyzed. Results The BP of the sepsis group treated with MB showed a slight improvement in the first hour after treatment; however, a significant difference was not observed compared to the untreated sepsis group. Besides hemodynamic stability, the current study did not show symptomatic pulmonary hypertension, suggesting that MB was safe in neonates and children. An improvement in Base Excel (BE) levels after MB administration in septic animals may indicate a possible improvement in microcirculation. Conclusion The MB improved biomarkers related to septic shock prognosis, although an improvement in the blood levels could not be detected. MB might be a beneficial drug for hemodynamic instability in infants.
  • A meta-analysis of the effect of Sjögren′s syndrome on adverse pregnancy outcomes Original Articles

    Geng, Baoqing; Zhang, Keyue; Huang, Xianqian; Chen, Yong

    Resumo em Inglês:

    Abstract Objective This study aimed to assess the correlation between Sjögren′s Syndrome (SS) and adverse pregnancy outcomes, with the aim of providing a basis for preconception and pregnancy interventions in women with SS. Methods A search of electronic databases in English and Chinese databases from January 2005 to December 2021, was conducted to collect the literature of case-control studies or cohort studies on the association between SS and pregnancy outcome studies. Literature inclusion and data extraction were performed according to established criteria, and the Newcastle-Ottawa scale was used to evaluate the quality of the literature. Stata 15 software was used for meta-analysis. Results A total of nine papers were included in this study. Meta-analysis results showed that SS was associated with spontaneous abortion (RR = 8.85, 95% CI 3.10‒25.26), preterm birth (RR = 2.27, 95% CI 1.46‒3.52), low birth mass (RR = 1.99, 95% CI 1.34‒2.97), and birth defects (RR = 4.28, 95% CI 3.08‒5.96). Conclusion SS can increase the incidence of adverse pregnancy outcomes.
  • Sudden unexpected death in Parkinson's disease: Insights from clinical practice Review Articles

    Scorza, Fulvio A; Guimarães-Marques, Marcia; Nejm, Mariana; Almeida, Antônio Carlos G de; Scorza, Carla A; Fiorini, Ana C; Finsterer, Josef

    Resumo em Inglês:

    Abstract Classified as the second most common neurodegenerative disorder associated with aging after Alzheimer's disease, Parkinson's disease (PD) is the most common movement disorder. In the last decade, despite advances in treatment, mortality rates linked with PD continued to reach significant figures. Available studies have shown that compared with healthy controls, patients with PD are accompanied by high rates of premature death. This is usually caused by factors such as pneumonia and cerebrovascular and cardiovascular diseases. Recently, it has been demonstrated that a significant proportion of patients with PD die suddenly. This is referred to as a sudden and unexpected death in PD (SUDPAR). Here, we focus on the magnitude of SUDPAR. Finally, it is important to learn more about SUDPAR for the implementation of effective prevention strategies.
  • From H1N1 to COVID-19: What we have seen in children with hemoglobinopathies Review Articles

    Oliveira, Claudia de Melo; Soares, Victor Jablonski; Rechenmacher, Ciliana; Daudt, Liane Esteves; Michalowski, Mariana Bohns

    Resumo em Inglês:

    Abstract This work aimed to better understand the impact of pandemics of respiratory viruses on children with hemoglobinopathies through a comprehensive review of the literature. MEDLINE, SCIELO, LILACS, and PUBMED were used as data sources to find articles without time period restrictions. Previous observations suggest that patients with hemoglobinopathies are a group especially susceptible to the complications of viral respiratory infections, with greater morbidity and mortality related to them. Within this context, this review found that, during the 2009 H1N1 pandemic, the risk of hospitalization in children and adults increased, especially in patients with a history of complications such as acute chest syndrome. In addition, the Coronavirus Disease 2019 (COVID-19) pandemic appears to have less repercussion among children with hemoglobinopathies compared to adults, similar to what is seen in the general population. In the H1N1 pandemic, patients with hemoglobinopathies behaved as a group more susceptible to complications, with increased morbidity and mortality. However, for COVID-19, the existing data to date on these patients do not show the same clinical impact. Thus, although these children deserve attention in case of infection due to their potential risks, they seem to have a favorable evolution. Highlights Children with hemoglobinopathies have less severe conditions with Coronavirus 2019 Disease (COVID-19) compared to adults, which is similar to that observed in the general population In the H1N1 pandemic, patients with hemoglobinopathies behaved as the group most susceptible to complications, with increased morbidity and mortality
  • Ischemic stroke in 455 COVID-19 patients Review Articles

    Finsterer, Josef; Scorza, Fulvio Alexandre; Scorza, Carla Alessandra; Fiorini, Ana Claudia

    Resumo em Inglês:

    ABSTRACT There is increasing evidence that COVID-19 can be associated with ischemic stroke (COVID-stroke). The frequency and pathogenesis of COVID-stroke, however, remains largely unknown. This narrative review aimed at summarizing and discussing current knowledge about frequency and pathogenesis of COVID-stroke in 455 patients collected from the literature. COVID-stroke occurs in all age groups and predominantly in males. The anterior circulation is more frequently affected than the posterior circulation. COVID-stroke is most frequently embolic. The severity of COVID-stroke ranges from NIHSS 3 to 32. Cardiovascular risk factors are highly prevalent in patients with COVID-stroke. COVID-stroke occurs simultaneously with the onset of pulmonary manifestations or up to 40 days later. Clinical manifestations of COVID-19 are most frequently mild or even absent. The majority of patients with COVID-stroke achieve complete or partial recovery, but in one-quarter of patients, the outcome is fatal. In conclusion, the frequency of ischemic stroke has not increased since the outbreak of the SARS-CoV-2 pandemic. COVID-stroke predominantly affects males and the anterior circulation. COVID-stroke is multifactorial but predominantly embolic and more frequently attributable to cardiovascular risk factors than to coagulopathy.
  • Arterial stiffness and atrial fibrillation: A review Review Articles

    Lage, Joao Gabriel Batista; Bortolotto, Alexandre Lemos; Scanavacca, Mauricio Ibrahim; Bortolotto, Luiz Aparecido; Darrieux, Francisco Carlos da Costa

    Resumo em Inglês:

    ABSTRACT Arterial stiffness has been investigated as part of the physiopathology of arterial hypertension since the 1970s. Its role in increasing the “pulsatile load” imposed over the Left Ventricle (LV) has been intensely studied recently and has helped in understanding the mechanisms of Atrial Fibrillation (AF) in hypertensive patients. This paper aims to review the main evidence on this issue and establish possible mechanisms involved in the development of AF in patients with arterial stiffness. A PubMed search was performed, and selected articles were searched for references focusing on this topic. In the long term, lower blood pressure levels allow for arterial wall remodeling, leading to a lower stiffness index. To this day, however, there are no available treatments that directly promote the lowering of arterial wall stiffness. Most classes of anti-hypertensive drugs ‒ with stronger evidence for beta-blockers and diuretics ‒ could be effective in reducing arterial stiffness. There is strong evidence demonstrating an association between arterial stiffness and AF. New studies focusing on arterial stiffness and pre-fibrillatory stages would strengthen this causality relation.
  • Efficacy and safety in the use of intraperitoneal hyperthermia chemotherapy and peritoneal cytoreductive surgery for pseudomyxoma peritonei from appendiceal neoplasm: A systematic review Review Articles

    Floriano, Idevaldo; Silvinato, Antônio; Reis, João C.; Cafalli, Claudia; Bernardo, Wanderley Marques

    Resumo em Inglês:

    Highlights Hyperthermia chemotherapy and cytoreductive surgery in patients with peritoneal pseudomyxoma.
  • Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review Review Articles

    Cortez, Vitor Santos; Moraes, Walter Augusto; Taba, João Victor; Condi, Alberto; Suzuki, Milena Oliveira; Nascimento, Fernanda Sayuri do; Pipek, Leonardo Zumerkorn; Mattos, Vitoria Carneiro de; Torsani, Matheus Belloni; Meyer, Alberto; Hsing, Wu Tu; Iuamoto, Leandro Ryuchi

    Resumo em Inglês:

    Abstract The objective of this study is to compare the effectiveness of dextrose-prolotherapy with other substances for pain relief in patients with primary knee osteoarthritis. The literature screening was done in January 2021 through Medline (PubMed), EMBASE, and Database of the National Institute of Health based on the following criteria: randomized clinical trials that subjected patients with primary knee osteoarthritis who underwent treatment with dextrose-prolotherapy and other substances for pain relief. Paired reviewers independently identified 3381 articles and included 8 trials that met the eligibility criteria. According to the findings of this review, participants that underwent dextrose-prolotherapy showed improvements between baseline and posterior assessments and when compared to saline injections, but when compared to other substances, the results were not clear. Although dextrose-prolotherapy is a useful treatment method by itself, it is still not possible to clearly affirm that it is superior or inferior to its counterparts. There is an urgent need for further studies to bring more evidence to the field. HIGHLIGHTS Dextrose injections promote deposition of collagen into injured structures through growth factors and inflammatory cells. Dextrose-prolotherapy is a useful treatment method, but it is not superior or inferior to its counterparts.
  • Medical errors, medical negligence and defensive medicine: A narrative review Review Articles

    Miziara, Ivan Dieb; Miziara, Carmen Silvia Molleis Galego

    Resumo em Inglês:

    Abstract Error in medicine and medical liability has a long history dating back to Antiquity. During the 19th Century, most lawsuits related to errors in treating surgical problems were settled. However, in the first half of the 20th Century, lawsuits claimed that mistakes were related to the doctor's action: the doctor made something wrong (errors of commission). In Brazil, medical error is defined as inappropriate conduct, including negligence and recklessness, that causes harm to the patient. The physician's fear of being suited is the reason for some practice named defensive Medicine (D.M.), defined as ordering unnecessary tests and procedures or avoiding treatments for patients considered at high-risk. Thus, this narrative review aims to analyze and describe the relationship between medical errors, medical negligence, and the practice of D.M. So, the authors propose procedures and attitudes to avoid medical errors and the approach of D.M.: a national focus to create leadership and research tools to enhance the knowledge base about patient safety; a reporting system that would help to identify and learn from errors; the use of a computer-based protocol reminder; some technological devices to help the medical practice (electronic prescribing and information technology systems); creating risk management programs in hospitals. Therefore, the authors conclude that the most critical attitude to avoid medical liability is a good and ethical medical practice with the proper use of technology, based on knowledge of scientific evidence and ethical principles of medicine - for the benefit of patients. HIGHLIGHTS This article defines medical errors and medical responsibility from a Brazilian perspective. This article calls attention to the risks of medical liability and the unethical use of defensive medicine. The authors propose some procedures and attitudes to avoid medical errors like the use of technology at the bedside and computer-based protocols. The authors state that a good and ethical medical practice can avoid medical liability.
  • Efficacy and safety of potassium-competitive acid blockers versus proton pump inhibitors as Helicobacter pylori eradication therapy: a meta-analysis of randomized clinical trials Review Articles

    Zhang, Mengran; Pang, Mingge; Zhang, Mei

    Resumo em Inglês:

    Abstract Background and aims: Potassium-Competitive Acid Blockers (P-CABs) have been used in Helicobacter pylori (H. pylori) eradication therapies in recent years. However, the efficacy and safety of P-CABs compared to ProtonPump Inhibitors (PPIs) in this setting remain controversial. Methods: The efficacy and safety of P-CABs and PPIs for H. pylori eradication were compared in a meta-analysis based on a systematic literature search of major electronic databases for relevant Randomized Controlled Trials (RCTs). Results: Seven studies and 1,168 patients were included. The pooled eradication rate determined by Intention-ToTreat (ITT) analysis was 90.2% for P-CAB-based and 75.5% for PPI-based triple therapy (pooled RR [95% CI] = 1.17 [1.08-1.28], p < 0.001). The Per-Protocol (PP) analysis also demonstrated significant superiority of P-CABs (pooled eradication rate = 92.4% vs. 77.8%; pooled RR [95% CI] = 1.14 [1.03–1.26], p < 0.01). In a subgroup evaluation, P-CABs were significantly better than PPIs as a first-line eradication therapy, in both the ITT analysis (pooled eradication rate = 91.8% vs. 76.4%; pooled RR [95% CI] = 1.18 [1.10-1.28], p < 0.0001) and the PP analysis (pooled eradication rate = 93.0% vs. 78.6%; pooled RR [95% CI] = 1.13 [1.02 –1.26], p < 0.05). However, P-CABs were not superior to PPIs when administered as salvage therapy, as determined in the ITT (75.0% vs. 66.0%, pooled RR [95% CI] = 1.11 [0.69–1.78], p = 0.66) and PP (85.7% vs. 70.0%, pooled RR [95% CI] = 1.20 [0.82–1.75], p = 0.34) analyses. In a subgroup analysis limited to Japanese patients, both the ITT analysis (pooled eradication rate = 89.6% vs. 73.9%; RR [95% CI] = 1.21 [1.14 –1.29], p < 0.01) and the PP analysis (pooled eradication rate = 92.0% vs. 75.7%; RR [95% CI] = 1.18 [1.06 –1.32], p < 0.01) showed that P-CABs were significantly superior compared to PPIs as triple eradication therapy. However, in the subgroup analysis of patients from other countries, there was no significant difference in either the ITT analysis (pooled eradication rate = 93.8% vs. 85.2%; RR [95% CI] = 1.10 [0.99-1.22], p = 0.07) or PP analysis (pooled eradication rate = 95.0% vs. 90.8%; RR [95% CI] = 1.05 [0.98–1.14], p = 0.17). The incidence of adverse events associated with the two regimens did not significantly differ (P-CABs vs. PPIs: 33.6% vs. 40.0%; RR [95% CI] = 0.84 [0.71‒1.00], p = 0.05). The incidence of serious adverse events and dropout rate due to adverse events also did not differ (p = 0.44 and p = 0.67, respectively). Conclusions: The efficacy of P-CAB-based triple therapy is superior to that of PPI-based triple therapy as a first-line approach to H. pylori eradication, particularly in Japanese patients. As salvage therapy, the efficacy of the two treatments did not significantly differ. The tolerability of P-CAB-based and PPI-based triple therapy was comparable, as was the incidence of adverse events. HIGHLIGHTS The efficacy of P-CAB-based triple therapy is superior to that of PPI-based triple therapy as a first-line approach to H. pylori eradication, particularly in Japanese patients. P-CABs were not superior to PPIs as a salvage triple eradication therapy. The safety and tolerability of P-CAB are comparable to PPI in H. pylori triple eradication therapies. Further large RCTs conducted in multiple regions and countries are necessary.
  • SARS-CoV-2 vaccinations reduce the prevalence of post-COVID Guillain-Barre syndrome Review Articles

    Finsterer, Josef; Matovu, Daniel; Scorza, Fulvio A.

    Resumo em Inglês:

    Abstract Guillain-Barre Syndrome (GBS) has been repeatedly reported as a neurological complication of COVID-19 (post-COVID GBS [PCG]). Whether the introduction of SARS-CoV-2 vaccines reduced the prevalence of PCG is unknown. This narrative review aimed to compare the number of published PCG cases between the second half of 2020 (no vaccination available) with those of the first half of 2021 (vaccination available). A total of 124 articles reported 300 patients with PCG between January 2020 and June 2021. The ages ranged from 7 to 94y. There was male dominance. The latency between the onset of COVID-19 and the onset of PCG ranged from -10 to 90d Acute, inflammatory, demyelinating polyneuropathy was diagnosed in 171 patients, acute, motor axonal neuropathy in 24, and acute, motor, and sensory axonal neuropathy in 16 patients. Regarding treatment, 241 patients received immunoglobulins, 28 patients' plasmaphereses, and 7 patients' steroids. Artificial ventilation was required in 59 patients. Full recovery was achieved in 42 cases, partial recovery in 163 cases, and 17 patients died. The number of published PCG patients fell from 192 in the second half of 2020 to 75 patients in the first half of 2021. It is concluded that the prevalence of PCG has decreased since the introduction of SARS-CoV-2 vaccines. SARS-CoV-2 vaccinations have a positive effect on the prevalence of PCG. HIGHLIGHTS SARS-CoV-2 infections can be complicated by Guillain-Barre Syndrome (GBS). The prevalence of SARS-CoV-2 associated GBS declined since the introduction of SARS-CoV-2 vaccines. The outcome of SARS-CoV-2 associated GBS is worse among those with comorbidities compared to those without.
  • Liver transplant after SARS-CoV-2 infection: A systematic review Review Articles

    Nacif, Lucas S.; Fernandes, Michel Ribeiro; Waisberg, Daniel R.; Pinheiro, Rafael S.; Rocha-Santos, Vinicius; Galvão, Flávio; Andraus, Wellington; Carneiro-D’Albuquerque, Luiz

    Resumo em Inglês:

    Abstract Background: The Coronavirus 19 (COVID-19) pandemic has dramatically impacted liver organ transplantation. The American Society of Transplantation recommends a minimum of 28 days after symptom resolution for organ donation. However, the exact time for transplantation for recipients is unknown. Considering that mortality on the waiting list for patients with MELD >25 or fulminant hepatitis is higher than that of COVID-19, the best time for surgery after SARS-CoV-2 infection remains undetermined. This study aims to expand the current knowledge regarding the Liver Transplantation (LT) time for patients after COVID-19 and to provide transplant physicians with essential decision-making tools to manage these critically ill patients during the pandemic. Methods: Systematic review of patients who underwent liver transplantation after diagnosis of COVID-19. The MEDLINE, PubMed, Cochrane, Lilacs, Embase, and Scielo databases were searched until June 20, 2021. The MESH terms used were “COVID-19” and “Liver transplantation”. Results: 558 articles were found; of these 13 articles and a total of 18 cases of COVID-19 prior to liver transplantation were reported. The mean age was 38.7±14.6, with male prevalence. Most had mild symptoms of COVID. Five patients have specific treatment for COVID-19 with convalescent plasm or remdesivir/oseltamivir, just one patient received hydroxychloroquine, and 12 patients received only symptomatic treatment. The median time between COVID-19 to LT was 19 days (13.5-44.5). Deceased donor liver transplantation accounted for 61% of cases, while living donor transplantation was 39%. Conclusion: Despite the concerns regarding the postoperative evolution, the mortality of patients with high MELD or fulminant hepatitis transplanted shortly after COVID-19 diagnosis does not seem to be higher. (PROSPERO, registration number = CRD42021261790)
  • Cervical cancer screening in low- and middle-income countries: A systematic review of economic evaluation studies Review Articles

    Casas, Carmen Phang Romero; Albuquerque, Rita de Cassia Ribeiro de; Loureiro, Rafaela Borge; Gollner, Angela Maria; Freitas, Marina Goncalves de; Duque, Graciela Paula do Nascimento; Viscondi, Juliana Yukari Kodaira

    Resumo em Inglês:

    Abstract Economic assessments are relevant to support the decision to incorporate more cost-effective strategies to reduce Cervical Cancer (CC) mortality. This systematic review analyzes the economic evaluation studies of CC prevention strategies (HPV DNA-based tests and conventional cytology) in low- and middle-income countries. Medline, EMBASE, CRD, and LILACS were searched for economic evaluation studies that reported cost and effectiveness measures of HPV DNA-based tests for CC screening and conventional cytology in women, without age, language, or publication date restrictions. Selection and data extraction were carried out independently. For comparability of results, cost-effectiveness measures were converted to international dollars (2019). Report quality was assessed using the CHEERS checklist. The Dominance Matrix Ranking (DRM) was used to analyze and interpret the results. The review included 15 studies from 12 countries, with cost-effectiveness analyzes from the health system’s perspective and a 3% discount rate. The strategies varied in age and frequency of screening. Most studies used the Markov analytical model, and the cost-benefit threshold was based on the per capita GDP of each country. The sensitivity analysis performed in most studies was deterministic. The completeness of the report was considered sufficient in most of the items evaluated by CHEERS. The Dominance Interpretation (DRM) varied; in 6 studies, the HPV test was dominant, 5 studies showed a weak dominance evaluating greater effectiveness of the HPV test at a higher cost, yet in 2 studies conventional cytology was dominant. Although the context-dependent nature of economic evaluations, this review points out the challenge of methodological standardization in the analytical models.
  • Maternal vaccination as an additional approach to improve the protection of the nursling: Anti-infective properties of breast milk Review Articles

    Zheng, Yingying; Correa-Silva, Simone; Palmeira, Patricia; Carneiro-Sampaio, Magda

    Resumo em Inglês:

    Abstract Human milk constitutes a secretion with unique functions of both nourishing the nursling and providing protection against enteric and respiratory infections, mainly due to its content of secretory IgA antibodies but also due to the presence of a plethora of bioactive factors. Specific IgA antibodies are produced locally by plasma cells derived from B lymphocytes that migrate from other mucosae to the mammary gland during lactation, particularly from the gastrointestinal and respiratory tracts. Therefore, here, the authors will provide a comprehensive review of the content and functions of different nutritional and bioactive anti-infectious components from breast milk, such as oligosaccharides, lactoferrin, haptocorrin, α-lactalbumin, k-casein, lysozyme, lactoperoxidase, mucin, fatty acids, defensins, cytokines and chemokines, hormones and growth factors, complement proteins, leukocytes and nucleic acids, including microRNAs, among many others, and the induction of antibody responses in breast milk after maternal vaccination with several licensed vaccines, including the anti-SARS-CoV-2 vaccine preparations used worldwide. Currently, in the midst of the pandemic, maternal vaccination has re-emerged as a crucial source of passive immunity to the neonate through the placenta and breastfeeding, considering that maternal vaccination can induce specific antibodies if performed during pregnancy and after delivery. There have been some reports in the literature about milk IgA antibodies induced by bacterial antigens or inactivated virus vaccines, such as anti-diphtheria-tetanus-pertussis, anti-influenza viruses, anti-pneumococcal and meningococcal polysaccharide preparations. Regarding anti-SARS-CoV-2 vaccines, most studies demonstrate elevated levels of specific IgA and IgG antibodies in milk with virus-neutralizing ability after maternal vaccination, which represents an additional approach to improve the protection of the nursling during the entire breastfeeding period.
  • We need to talk about critical care in Brazil Comments

    Batista Filho, Luiz Alberto Cerqueira; Randhawa, Varinder Kaur; Maciel, Alexandre Toledo; Coimbra, Marcelo Rocha
  • The impact of multivisceral liver resection on short- and long-term outcomes of patients with colorectal liver metastasis: A systematic review and meta-analysis Review Articles

    Silveira Junior, Sergio; Tustumi, Francisco; Magalhães, Daniel de Paiva; Jeismann, Vagner Birk; Fonseca, Gilton Marques; Kruger, Jaime Arthur Pirola; Coelho, Fabricio Ferreira; Herman, Paulo

    Resumo em Inglês:

    Abstract The impact of Multivisceral Liver Resection (MLR) on the outcome of patients with Colorectal Liver Metastasis (CRLM) is unclear. The present systematic review aimed to compare patients with CRLM who underwent MLR versus standard hepatectomy regarding short- and long-term outcomes. MLR is a feasible procedure but has a higher risk of major complications. MLR did not negatively affect long-term survival, suggesting that an extended resection is an option for potentially curative treatment for selected patients with CRLM.
  • MICRObiota on BILIOpancreatic malignant diseases [MICROBILIO]: A systematic review Review Articles

    Mattos, Vitoria Carneiro de; Nascimento, Fernanda Sayuri do; Suzuki, Milena Oliveira; Taba, Joao Victor; Pipek, Leonardo Zumerkorn; Moraes, Walter Augusto Fabio; Cortez, Vitor Santos; Kubrusly, Marcia Saldanha; Torsani, Matheus Belloni; Iuamoto, Leandro; Hsing, Wu Tu; Carneiro-D’Albuquerque, Luiz Augusto; Meyer, Alberto; Andraus, Wellington

    Resumo em Inglês:

    Abstract Introduction: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). Methods: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. Results: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies’ results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. Conclusion: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.
  • Effectiveness of neuromuscular electrostimulation in COPD subjects on mechanical ventilation. A systematic review and meta-analysis Review Articles

    Gutierrez-Arias, Ruvistay; Jalil, Yorschua; Fuentes-Aspe, Rocío; Seron, Pamela

    Resumo em Inglês:

    Abstract Objective: To estimate the effectiveness of Neuromuscular Electrostimulation (NMES) in adults with COPD undergoing MV. Method: A sensitive search was performed in MEDLINE, Embase, CENTRAL, CINAHL and other resources. Randomized Controlled Clinical Trials (RCTs) or non-RCTs that enrolled adults with COPD on MV due to an exacerbation of their disease were included. Two independent reviewers screened, extracted information, and assessed the risk of bias (RoB 2 tool) and the certainty of evidence (GRADE approach) from the included studies. Results: Four RCTs (144 participants) were included. Subjects who underwent NMES were able to move from bed to chair independently in less time (MD = 4.98 days less; 95% CI -8.55 to -1.47; 2 RCTs; low certainty of the evidence) and they were fewer days on MV (MD = 2.89 days less; 95% CI -4.58 to -1.21); 3 RCTs; low certainty of the evidence) than the control group. However, the effect of NMES on muscle strength is unclear (very low certainty of the evidence). Conclusions: NMES may improve functional independence and decrease MV time in adults with COPD; however, its effectiveness on muscle strength is uncertain. More and better RCTs are needed to determine with greater certainty the effectiveness of NMES in this population.
  • Inhibition of Toll-like Receptor-4 expression for amelioration of myocardial injury in diabetes: A meta-analysis Review Articles

    Yuan, Jinxin; Yin, Xingwen; Jiang, Hua

    Resumo em Inglês:

    Abstract To understand the relationship between the inhibition of Toll-Like Receptor-4 (TLR4) expression levels and diabetic myocardial injury, studies on TLR4 and diabetic myocardial injury in the China National Knowledge Internet (CNKI), WanFang database, VIP Database, PubMed, The Cochrane Library, Web of Science, and other databases were explored (retrieval details: November 2020). A meta-analysis of the selected literature was performed using the RevMan 5.4 software to detect publication bias using funnel plots and conduct a sensitivity analysis. Nine publications were finally included in this study, of which six included data on Heart Weight/Body Weight (HW/BW) indexes, and five included data on Left Ventricular Systolic Pressure (LVSP) and Left Ventricular End-Diastolic Pressure (LVEDP) indices. The meta-analysis showed that HW/BW was significantly reduced after the suppression of TLR4 expression (Standardized Mean Difference [SMD = 1.9], 95% CI between 0.59 and 3.21, p = 0.004), LVSP was significantly improved (SMD = -2.39, 95% CI between -4.32 and -0.46, p = 0.02), and LVEDP was significantly reduced (SMD = 2.88, 95% CI between 1.05 and 4.71, p = 0.002). The TLR4 signaling pathway plays an essential role in the pathogenesis of Diabetic Cardiomyopathy (DCM). Inhibition of TLR4 expression can improve the degree of cardiac impairment. TLR4 may become a new target for the treatment of DCM, and the use of TLR4 inhibitors may prove to be a novel strategy for therapeutic research.
  • Patient with agammaglobulinemia produces anti-SARS-CoV-2 reactive T-cells after CoronaVac vaccine Comments

    Oshiro, Telma Miyuki; Silva, Lais Teodoro da; Ortega, Marina Mazzilli; Perazzio, Sandro Felix; Duarte, Alberto Jose da Silva; Carneiro-Sampaio, Magda
  • Stigma in Parkinson's disease: Placing it outside the body Comments

    Rosa, Tomás de la; Scorza, Fúlvio Alexandre
  • Artificial intelligence in the medical profession: ready or not, here AI comes Comments

    Pucchio, Aidan; Papa, Joshua Del; Moraes, Fabio Ynoe de
  • Time-to-event assessment for the discovery of the proper prognostic value of clinical biomarkers optimized for COVID-19 Comments

    Ferreira Junior, José Raniery
  • Care coordination in pediatrics: Experience of the outpatient clinic for Children with Special Health Care Needs (CSHCN) Comments

    Ferrer, Ana Paula Scoleze; Scaramuzzi, Daleth Rodrigues; Bourroul, Maria Lúcia M.; Zuccolotto, Sandra M.C.; Grisi, Sandra J.F.E.
  • Palliative care in the COVID-19 pandemic: Strategy of HCFMUSP Comments

    Carvalho, Ricardo Tavares de; Crispim, Douglas Henrique; Franck, Ednalda Maria; Santi, Daniel Battacini Dei; Anagusko, Sergio Seiki; Fukuda, Márcio Veronesi; Cavalcante, Luciana Suelly Barros; Jales, Sumatra Melo da Costa Pereira; Queiroz, Mônica Estuque Garcia de; Bonfá, Eloisa Silva Dutra de Oliveira
  • Long COVID-19: Rethinking mental health Comments

    Gallegos, Miguel; Portillo, Nelson; Martino, Pablo; Cervigni, Mauricio
  • Sudden unexpected death in epilepsy and abnormal glucose metabolism in the rat insular cortex: A brain within the heart Comments

    Scorza, Fulvio A.; Almeida, Antonio-Carlos G. de; Scorza, Carla A.; Finsterer, Josef
  • Comments: Myositis-specific and myositis-associated autoantibody profiles and their clinical associations in a large series of patients with polymyositis and dermatomyositis Comments

    Ferreira, Bruno Silva de Araujo; Cunha, Bernardo Matos da; Moreira, Larissa Aniceto; Fonseca, Michel Fabrício Silveiro e; Cavalcante, Eduardo Boiteux Uchoa
  • The implication of cardio-oncology on Parkinson's disease: answers begin to emerge Comments

    Scorza, Fulvio A.; Almeida, Antonio-Carlos G. de; Finsterer, Josef; Hajjar, Ludhmila A.
  • “Similia Similibus Curentur”: The scientific grounding of the homeopathic therapeutic principle through the systematic study of the rebound effect of modern drugs Comments

    Teixeira, Marcus Zulian

    Resumo em Inglês:

    Highlights Homeopathy employs the principle of therapeutic similitude as a method of treatment. Primary action of drugs is followed by secondary and opposite reaction of the organism. This secondary and opposite reaction of the organism is namely the rebound effect of drugs. Homeopathy employs the rebound effect of drugs in a therapeutic way.
  • Guillain-Barre syndrome related to SARS-CoV-2 vaccinations Comments

    Finsterer, Josef; Scorza, Carla A.; Scorza, Fulvio A.
  • Developmental and Behavioral Pediatrics: an emerging subspecialty. Experience of the Instituto da Criança e do Adolescente — ICr-HCFMUSP Comments

    Ferrer, Ana Paula Scoleze; Grisi, Sandra Josefina Ferraz Ellero
  • Erratum to Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital” [Clinics. 2021;76:e3511] Errata

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