Artigos e Materiais de Revistas Científicas - LIM/26

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A coleção de Artigos e Materiais de Revistas Científicas engloba artigos originais, artigos de revisão, artigos de atualização, artigos técnicos, relatos de experiências, resenhas, ensaios, editoriais, cartas ao editor, debates, notas científicas e técnicas, depoimentos, entrevistas e pontos de vista. Consideram-se como artigos científicos originais os trabalhos redigidos para divulgação de informações e resultados sobre determinada pesquisa científica, publicados em periódico científico após avaliação por outros pesquisadores.

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Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy
(2024) PIRES, Daniela A.; BRANDAO-RANGEL, Maysa A. R.; SILVA-REIS, Anamei; OLIMPIO, Fabiana R. S.; AIMBIRE, Flavio; OLIVEIRA, Carlos R.; MATEUS-SILVA, Jose R.; ZAMARIOLI, Lucas S.; BACHI, Andre L. L.; BELLA, Yanesko F.; SANTOS, Juliana M. B.; BINCOLETTO, Claudia; JR, Antonio Herbert Lancha; VIEIRA, Rodolfo P.
Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 mu g/mL and 10 mu g/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 mu M), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 x 10(5) cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 mu g/mL, p < 0.01 and 10 g/mL, p < 0.01) and tumor necrosis factor (TNF) (5 g/mL, p < 0.01 and 10 g/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 g/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 g/mL, p < 0.01 and 10 g/mL, p < 0.01), while only the 10 g/mL dose of vitamin C induced the release of Klotho (10 mu g/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 g/mL, p < 0.01 and 10 g/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.
Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic
(2024) RITTO, Ana Paula; ARAUJO, Adriana Ladeira de; CARVALHO, Carlos Roberto Ribeiro de; SOUZA, Heraldo Possolo De; FAVARETTO, Patricia Manga e Silva; SABOYA, Vivian Renata Boldrim; GARCIA, Michelle Louvaes; KULIKOWSKI, Leslie Domenici; KALLAS, Esper Georges; PEREIRA, Antonio Jose Rodrigues; COBELLO JUNIOR, Vilson; SILVA, Katia Regina; ABDALLA, Eidi Raquel Franco; SEGURADO, Aluisio Augusto Cotrim; SABINO, Ester Cerdeira; RIBEIRO JUNIOR, Ulysses; FRANCISCO, Rossana Pulcineli Vieira; MIETHKE-MORAIS, Anna; LEVIN, Anna Sara Shafferman; SAWAMURA, Marcio Valente Yamada; FERREIRA, Juliana Carvalho; SILVA, Clovis Artur; MAUAD, Thais; GOUVEIA, Nelson da Cruz; LETAIF, Leila Suemi Harima; BEGO, Marco Antonio; BATTISTELLA, Linamara Rizzo; DUARTE, Alberto Jose da Silva; SEELAENDER, Marilia Cerqueira Leite; MARCHINI, Julio; FORLENZA, Orestes Vicente; ROCHA, Vanderson Geraldo; MENDES-CORREA, Maria Cassia; COSTA, Silvia Figueiredo; CERRI, Giovanni Guido; BONFA, Eloisa Silva Dutra de Oliveira; CHAMMAS, Roger; BARROS FILHO, Tarcisio Eloy Pessoa de; BUSATTO FILHO, Geraldo
Introduction The COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.Methods At the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.Results Over the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020-2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.Discussion Research is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.
Effect of Menstrual Cycle Phase on Fuel Oxidation Post HIT in Women Reproductive Age: A Pilot Study
(2023) FRIENTES, C. S.; MARQUEZI, M. L.; APARECIDO, J. M. L.; CASCAPERA, M. S.; ROGERI, P. S.; LANCHA JUNIOR, A. H.
Women of childbearing age have variations in substrate oxidation rates that can lead to overweight, type II diabetes, and other conditions that may be associated with metabolic inflexibility and the variations in estrogen concentrations observed during the monthly ovarian cycle. Purpose: This study aimed to verify and compare the influence of eight treadmill high-intensity interval training (HIT) sessions on carbohydrate and lipid oxidation rates (CHOox and LIPox, respectively) and intensities of ventilatory anaerobic thresholds (VATs) of women in different phases of the monthly ovarian cycle. Methods: Eleven irregularly active women performed incremental treadmill exercise testing followed by submaximal work-rate running for 45 min to determine VATs, VO2peak, peak velocity (Vpeak), and substrate oxidation rates, before and after a training period, in different phases of their monthly ovarian cycle (follicular phase group, FL, n = 6; luteal phase group, LT, n = 5). The training period consisted of eight HIT sessions, composed each one of eight sets of 60 s running at 100%Vpeak interspersed by 75 s recovery every 48 h. Results: Our results showed no significant differences in VATs intensities between groups. The comparison between groups showed significant differences in relative energy derived from CHO pre- and post-training of −61.42% and −59.26%, respectively, and LIP pre- and post-training of 27.46% and 34.41%, respectively. The relative energy derived from CHO after the training period was 18.89% and 25.50% higher for FL and LT, respectively; consequently, the relative energy derived from LIPox after the training period was 8,45% and 3.46% lower for FL and LT, respectively. Over the training period, Vpeak was ~13.5 km/h, which produced the relative intensities of ~89%VO2peak e ~93%HRpeak for both groups. Conclusion: The monthly ovarian cycle phases promote significant changes in substrate oxidation rates leading to a decrease in CHOox. High-intensity interval training can minimize the differences observed and constitute an alternative intervention.
Diameter of ureteral access sheath and ureteral stenosis development: a systematic review
(2023) PISSAIA, Tamires Battistini; BELKOVSKY, Mikhael; PASSEROTTI, Carlo Camargo; ARTIFON, Everton Luiz de Almeida; OTOCH, Jose Pinhata; CRUZ, Jose Arnaldo Shiomi da
Purpose: Ureteral access sheaths (UAS) are widely used in ureteroscopy. UAS are believed to pose a significant risk for ureteral stenosis due to ureteral mucosal compression, but little evidence supports this claim. Our systematic review aimed to investigate the relationship between different UAS diameters and stenosis risk. Methods: A systematic search was conducted in PubMed, Embase, Web of Science, Scopus, and Cochrane, from its inception to May 2023. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines were followed. chi 2 test was performed to compare the prevalence within the groups. Results: Six nonrandomized trials and one randomized, with a total of 962 patients, were included. The overall incidence of ureteral stenosis of 0.9%. UAS sizes were: 9.5/11.5Fr, 10/12Fr, 11/13Fr, 12/14Fr, and 14/16Fr. Within each subgroup, the incidence of ureteral stenosis was: 0.4, 8, 0, 1, and 1% (p = 0.099). No trend for stenosis was observed among larger UAS. Conclusion: In this systematic review, no relationship between UAS diameter and incidence of ureteral stenosis was observed. Nonetheless, additional randomized controlled trials are required to support this finding.
EUS-guided choledochoduodenostomy for malignant biliary obstruction: A multicenter comparative study between plastic and metallic stents
(2023) SILVA, Rodrigo Roda Rodrigues da; FACANALI JUNIOR, Marcio Roberto; BRUNALDI, Vitor Ottoboni; OTOCH, Jose Pinhata; ROCHA, Ana Carolina Aguiar; ARTIFON, Everson Luiz de Almeida
Background and Objectives: EUS-guided choledochoduodenostomy (EUS-CDS) is commonly employed to address malignant biliary obstruction (MBO) after a failed ERCP. In this context, both self-expandable metallic stents (SEMSs) and double-pigtail stents (DPSs) are suitable devices. However, few data comparing the outcomes of SEMS and DPS exist. Therefore, we aimed to compare the efficacy and safety of SEMS and DPS at performing EUS-CDS. Methods: We conducted a multicenter retrospective cohort study between March 2014 and March 2019. Patients diagnosed with MBO were considered eligible after at least one failed ERCP attempt. Clinical success was defined as a drop of direct bilirubin levels >= 50% at 7 and 30 postprocedural days. Adverse events (AEs) were categorized as early (<= 7 days) or late (> 7 days). The severity of AEs was graded as mild, moderate, or severe. Results: Forty patients were included, 24 in the SEMS group and 16 in the DPS group. Demographic data were similar between the groups. Technical success rates and clinical success rates at 7 and 30 days were similar between the groups. Similarly, we found no statistical difference in the incidence of early or late AEs. However, there were two severe AEs (intracavitary migration) in the DPS group and none in the SEMS cohort. Finally, there was no difference in median survival (DPS 117 days vs. SEMS 217 days; P = 0.99). Conclusion: EUS-guided CDS is an excellent alternative to achieve biliary drainage after a failed ERCP for MBO. There is no significant difference regarding the effectiveness and safety of SEMS and DPS in this context.
Does displacement of lower pole stones during retrograde intrarenal surgery improves stone-free status? A systematic review and meta-analysis
(2023) SANTANA, Roberto Nogueira; PORTO, Breno Cordeiro; PASSEROTTI, Carlo Camargo; ARTIFON, Everson Luiz de Almeida; OTOCH, Jose Pinhata; CRUZ, Jose Arnaldo Shiomi da
Purpose: Kidney stones are one of the most common urological diseases worldwide. The size and location of the stone are the most important factors in determining the most suitable treatment options. The aim of this review was to evaluate the displacement of lower pole stones. Methods: Three studies assessing the efficacy of translocating kidney stones from the lower pole of the kidney to other locations during retrograde intrarenal surgery published in the last 20 years were included. A systematic search was conducted in the PubMed, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), and Web of Science databases using the following search terms: ""Lower pole,"" ""Lithotripsy."" Meta-analysis was performed using Review Manager version 5.4. Results: Stone-free rates were improved through displacement (odds ratio - OR = -0.15; 95% confidence interval-95%CI -0.24--0.05; p = 0.002; I2 = 21%), but at the cost of increased surgical duration (mean difference = -12.50; 95%CI -24.06--0.95; p = 0.03; I2 = 94%). Although this represents a potentially negative outcome, the improvement in clearance rates justifies the additional investment of time and effort. Conclusion: Displacement of lower pole kidney stones for subsequent lithotripsy brings significant benefits in terms of stone-free rate, with no difference in laser energy usage. However, it results in increased surgical time. Despite these factors, the benefits to patients undergoing the procedure are substantial.
Public and private fundraising as a tool for professional development: What is fundraising?
(2023) ARTIFON, Everson Luiz de Almeida; MAGON, Mariana Goncalves; JR, Marcio Roberto Facanali; MONTERO, Edna Frasson de Souza
Comparing financing models for supplementary healthcare in appendectomy: activity-based costing (fee-for-service) vs. diagnosis related group remuneration (bundled payment) - a systematic review and meta-analysis
(2023) LINO, Andre de Arimateia de Souza; CRUZ, Jose Arnaldo Shiomi da; PORTO, Breno Cordeiro; NOGUEIRA, Rhuan Pimentel; OTOCH, Jose Pinhata; ARTIFON, Everson Luiz de Almeida
Purpose: In Brazil, healthcare services traditionally follow a fee-for-service (FFS) payment system, in which each medical procedure incurs a separate charge. An alternative reimbursement with the aim of reducing costs is diagnosis related group (DRG) remuneration, in which all patient care is covered by a fixed amount. This work aimed to perform a systematic review followed by meta-analysis to assess the effectiveness of the Budled Payment for Care Improvement (BPCI) versus FFS. Methods: Our work was performed following the items of the PRISMA report. We included only observational trials, and the primary outcome assessed was the effectiveness of FFS and DRG in appendectomy considering complications. We also assessed the costs and length of hospital stay. Meta-analysis was performed with Rev Man version 5.4. Results: Out of 735 initially identified articles, six met the eligibility criteria. We demonstrated a shorter hospital stay associated with the DRG model (mean difference = 0.39; 95% confidence interval - 95%CI - 0.38-0.40; p < 0.00001; I2 = 0%), however the hospital readmission rate was higher in this model (odds ratio = 1.57; 95%CI 1.02-2.44, p = 0.04; I2 = 90%). Conclusion: This study reveals a potential decrease in the length of stay for appendectomy patients using the DRG approach. However, no significant differences were observed in other outcomes analysis between the two approaches.
Use of artificial intelligence for sepsis risk prediction after flexible ureteroscopy: a systematic review
(2023) ALVES, BEATRIZ MESALIRA; BELKOVSKY, MIKHAEL; PASSEROTTI, CARLO CAMARGO; ARTIFON, EVERSON LUIZ DE ALMEIDA; OTOCH, JOSÉ PINHATA; CRUZ, JOSÉ ARNALDO SHIOMI DA
ABSTRACT Introduction: flexible ureteroscopy is a minimally invasive surgical technique used for the treatment of renal lithiasis. Postoperative urosepsis is a rare but potentially fatal complication. Traditional models used to predict the risk of this condition have limited accuracy, while models based on artificial intelligence are more promising. The objective of this study is to carry out a systematic review regarding the use of artificial intelligence to detect the risk of sepsis in patients with renal lithiasis undergoing flexible ureteroscopy. Methods: the literature review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The keyword search was performed in MEDLINE, Embase, Web of Science and Scopus and resulted in a total of 2,496 articles, of which 2 met the inclusion criteria. Results: both studies used artificial intelligence models to predict the risk of sepsis after flexible uteroscopy. The first had a sample of 114 patients and was based on clinical and laboratory parameters. The second had an initial sample of 132 patients and was based on preoperative computed tomography images. Both obtained good measurements of Area Under the Curve (AUC), sensitivity and specificity, demonstrating good performance. Conclusion: artificial intelligence provides multiple effective strategies for sepsis risk stratification in patients undergoing urological procedures for renal lithiasis, although further studies are needed.
Effect of photobiomodulation on neuropathic pain of diabetic origin: a narrative review of the literature
(2023) SILVA, Alisson Pereira da; OLIVEIRA, Victoria Regina da Silva; DALE, Camila Squarzoni
To update the literature on the effectiveness of photobiomodulation (PBM) therapy in relieving pain in patients with diabetic peripheral neuropathy (DPN) compared to the effects of post-intervention, control/placebo groups, and other therapies. Search on the following databases: PORTAL PERIODICOS CAPES, PUBMED, GOOGLE ACADEMIC/SCHOLAR, SCOPUS, SCIELO, CENTRAL, and MEDLINE. Manual search: 1) manually capture the references of relevant articles originally selected to be included in the eligible studies. Two independent researchers performed the screening and selection of studies, methods assessment, and data extraction with unblinded authors and impressions. Subsequently, the full text of the originally selected studies was screened. The screening form registered the criteria for excluding literature from the full-text screening. The screening resulted in a total of 1692 citations. Out of these, 1402 citations were examined for titles and abstracts, followed by the removal of duplicated studies; therefore, 68 articles remained for full-text evaluation. 54 articles were excluded after full-text screening. Fourteen articles met the selection criteria, hence being selected and included in this narrative review. PBM showed to be a promising modality in relieving painful symptoms in DPN, especially when implemented in combination with other therapies, by improving the quality of life of diabetic patients.
Cancer-Related Fatigue Outcome Measures in Integrative Oncology: Evidence for Practice and Research Recommendations
(2022) GENTILE, Danielle; BEELER, Dori; WANG, Xin Shelley; BEN-ARYE, Eran; ZICK, Suzanna; BAO, Ting; CARLSON, Linda E.; GHELMAN, Ricardo; MASTER, Viraj A.; TRIPATHY, Debu; ZHI, W. Iris
Cancer-related fatigue (CRF) is one of the most common symptoms across the cancer continuum and is often underreported and undertreated. Defined as a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or its treatment, CRF includes physical, emotional, cognitive, and spiritual dimensions. Patient-reported outcome (PRO) measures are the most widely used tool to screen for and assess fatigue and the associated negative impacts on quality of life. However, selecting subjective CRF measures can be complex. This has resulted in the availability of and inconsistent use of numerous PROs, limiting the ability to cross-compare outcomes clinically and within research. To address this, the PROs that are most widely reported in the literature are recommended to support the standardization of a core set of validated measures. The National Comprehensive Cancer Network single-item tool for clinical significance is recommended for quick use in clinical environments; the Brief Fatigue Inventory allows for fast, easy, helpful cutoffs on severity threshold for triage, and measures both severity and interference with daily functioning; while the MD Anderson Symptom Inventory allows for multisymptomatic assessment. In addition, a fundamental consideration for any PRO use is the administrative burden on the patient and clinician. In this review, we aim to summarize current, validated PROs specific to CRF to aid clinicians and researchers in patient care and in study design and implementation. We conclude with suggestions for future directions in CRF research that can increase the possibility for long-term impact on future guidelines of fatigue management.
Assessing the safety and use of medicinal herbs during pregnancy: a cross-sectional study in São Paulo, Brazil
(2023) IM, Hyea Bin; GHELMAN, Ricardo; PORTELLA, Caio Fabio Schlechta; HWANG, Jung Hye; CHOI, Dain; KUNWOR, Sangita Karki; MORAES, Sandra Dircinha Teixeira de Araujo; HAN, Dongwoon
Background: Despite the lack of evidence supporting the safety and clinical efficacy of herbal medicine (HM), its use among pregnant women continues to increase. Given the high prevalence of contraindicated herbs among the pregnant population in Brazil, it is crucial to examine the use of HM and evaluate its safety based on the current scientific literature to ensure that women are using HM appropriately.Methods: A cross-sectional study was conducted from October 2022 to January 2023 at a public teaching hospital in Sao Paulo, Brazil. A total of 333 postpartum women in the postnatal wards and postnatal clinic were interviewed using a semi-structured questionnaire. The survey instrument consisted of 51 items covering the use of HM during pregnancy, sociodemographic and health-related characteristics, COVID-19 experiences, and pregnancy outcomes. For data analysis, chi-square and multivariate logistic regression were conducted using SPSS ver. 26.0.Results: Approximately 20% of respondents reported using HM during their most recent pregnancy, with a higher use observed among women from ethnic minority groups and those with prior HM experience. Among the 20 medicinal herbs identified, 40% were found to be contraindicated or recommended for use with caution during pregnancy. However, only half of the women discussed their HM use with obstetric care providers.Conclusion: This study emphasizes the continued public health concern regarding the use of contraindicated or potentially harmful HM among pregnant women in Brazil, highlighting the need for sustained efforts to reduce the risk of inappropriate HM use. By updating antenatal care guidelines based on the latest scientific evidence, healthcare providers can make informed clinical decisions and effectively monitor pregnant women's HM use, ultimately promoting safer and more effective healthcare practices.
EUS-Guided Biliary Drainage Versus ERCP in Malignant Biliary Obstruction Before Hepatobiliary Surgery
(2023) TYBERG, Amy; SARKAR, Avik; SHAHID, Haroon M.; SHAH-KHAN, Sardar M.; GAIDHANE, Monica; SIMON, Alexa; EISENBERG, Ian A.; LAJIN, Michael; KARAGYOZOV, Petko; LIAO, Kelvin; PATEL, Roohi; ZHAO, Eric; MARTINEZ, Ma Guadalupe; ARTIFON, Everson L.; LINO, Andre D.; VANELLA, Giuseppe; ARCIDIACONO, Paolo G.; KAHALEH, Michel
Introduction:Endoscopic ultrasound-guided biliary drainage (EUS-BD) is the procedure of choice for patients who cannot undergo endoscopic retrograde cholangiopancreatography (ERCP). The outcomes of patients undergoing surgery after EUS-BD for malignancy are unknown.Methods:We conducted an international, multicenter retrospective comparative study of patients who underwent hepatobiliary surgery after having undergone EUS-BD or ERCP from 6 tertiary care centers. Patient demographics, procedural data, and follow-up care were collected in a registry.Results:One hundred forty-five patients were included: EUS-BD n=58 (mean age 66, 45% male), ERCP n=87 (mean age 68, 53% male). The majority of patients had pancreatic cancer, cholangiocarcinoma, or gallbladder malignancy. In the EUS-BD group, 29 patients had hepaticogastrostomy, 24 had choledochoduodenostomy, and 5 had rendezvous technique done. The most common surgery was Whipple in both groups (n=41 EUS-BD, n=56 ERCP) followed by partial hepatectomy (n=7 EUS-BD, n=14 ERCP) and cholecystectomy (n=2 EUS-BD, n=2 ERCP). Endoscopy clinical success was comparable in both groups (98% EUS-BD, 94% ERCP). Adverse event rates were similar in both groups: EUS-BD (n=10, 17%) and ERCP (n=23, 26%). Surgery technical success and clinical success were significantly higher in the EUS-BD group compared with the ERCP group (97% vs. 83%, 97% vs. 75%). Total Hospital stay from surgery to discharge was significantly higher in the ERCP group (19 d vs. 10 d, P=0.0082).Discussion:Undergoing EUS-BD versus ERCP before hepatobiliary surgery is associated with fewer repeat endoscopic interventions, shorter duration between endoscopy and surgical intervention, higher rates of surgical clinical success, and shorter length of hospital stay after surgery.
Understanding yellow fever-associated myocardial injury: an autopsy study
(2023) GIUGNI, Fernando Rabioglio; DEMARCHIAIELLO, Vera; FARIA, Caroline Silverio; POUR, Shahab Zaki; CUNHA, Marielton dos Passos; GIUGNI, Melina Valdo; PINESI, Henrique Trombini; LEDESMA, Felipe Lourenco; MORAIS, Carolina Esteves; HO, Yeh-Li; SZTAJNBOK, Jaques; FERNEZLIAN, Sandra de Morais; SILVA, Luiz Fernando Ferraz da; MAUAD, Thais; ALVES, Venancio Avancini Ferreira; SALDIVA, Paulo Hilario do Nascimento; ANTONANGELO, Leila; DOLHNIKOFF, Marisa; DUARTE-NETO, Amaro Nunes
Background Yellow fever (YF) is a viral hemorrhagic fever, endemic in parts of South America and Africa. There is scarce evidence about the pathogenesis of the myocardial injury. The objective of this study is to evaluate the cardiac pathology in fatal cases of YF.Methods This retrospective autopsy study included cases from the Sao Paulo (Brazil) epidemic of 2017-2019. We reviewed medical records and performed cardiac tissue histopathological evaluation, electron microscopy, immunohistochemical assays, RT-qPCR for YF virus (YFV)-RNA, and proteomics analysis on inflammatory and endothelial biomarkers.Findings Seventy-three confirmed YF cases with a median age of 48 (34-60) years were included. We observed myocardial fibrosis in 68 (93.2%) patients; cardiomyocyte hypertrophy in 68 (93.2%); endothelial alterations in 67 (91.8%); fiber necrosis in 50 (68.5%); viral myocarditis in 9 (12.3%); and secondary myocarditis in 5 (6.8%). Four out of five patients with 17DD vaccine-associated viscerotropic disease presented with myocarditis. The cardiac conduction system showed edema, hemorrhages and endothelial fibrinoid necrosis. Immunohistochemistry detected CD68-positive inflammatory interstitial cells and YFV antigens in endothelial and inflammatory cells. YFV-RNA was detected positive in 95.7% of the cardiac samples. The proteomics analysis demonstrated that YF patients had higher levels of multiple inflammatory and endothelial biomarkers in comparison to cardiovascular controls, and higher levels of interferon gamma-induced protein 10 (IP-10) in comparison to sepsis (p = 0.01) and cardiovascular controls (p < 0.001) in Dunn test.Interpretation Myocardial injury is frequent in severe YF, due to multifactorial mechanisms, including direct YFV-mediated damage, endothelial cell injury, and inflammatory response, with a possible prominent role for IP-10.
COVID-19 induces more pronounced extracellular matrix deposition than other causes of ARDS
(2023) COSTA, Natalia de Souza Xavier; RIBEIRO JUNIOR, Gabriel; NASCIMENTO, Ellen Caroline Toledo do; BRITO, Jose Mara de; ANTONANGELO, Leila; FARIA, Caroline Silverio; MONTEIRO, Jhonatas Sirino; SETUBAL, Joao Carlos; PINHO, Joao Renato Rebello; PEREIRA, Roberta Verciano; SEELAENDER, Marilia; CASTRO, Gabriela Salim de; LIMA, Joanna D. C. C.; MONTEIRO, Renata Aparecida de Almeida; DUARTE-NETO, Amaro Nunes; SALDIVA, Paulo Hilario Nascimento; SILVA, Luiz Fernando Ferraz da; DOLHNIKOFF, Marisa; MAUAD, Thais
BackgroundLung fibrosis is a major concern in severe COVID-19 patients undergoing mechanical ventilation (MV). Lung fibrosis frequency in post-COVID syndrome is highly variable and even if the risk is proportionally small, many patients could be affected. However, there is still no data on lung extracellular matrix (ECM) composition in severe COVID-19 and whether it is different from other aetiologies of ARDS.MethodsWe have quantified different ECM elements and TGF-beta expression in lung tissue of 28 fatal COVID-19 cases and compared to 27 patients that died of other causes of ARDS, divided according to MV duration (up to six days or seven days or more). In COVID-19 cases, ECM elements were correlated with lung transcriptomics and cytokines profile.ResultsWe observed that COVID-19 cases presented significant increased deposition of collagen, fibronectin, versican, and TGF-beta, and decreased decorin density when compared to non-COVID-19 cases of similar MV duration. TGF-beta was precociously increased in COVID-19 patients with MV duration up to six days. Lung collagen was higher in women with COVID-19, with a transition of upregulated genes related to fibrillogenesis to collagen production and ECM disassembly along the MV course.ConclusionsFatal COVID-19 is associated with an early TGF-beta expression lung environment after the MV onset, followed by a disordered ECM assembly. This uncontrolled process resulted in a prominent collagen deposition when compared to other causes of ARDS. Our data provides pathological substrates to better understand the high prevalence of pulmonary abnormalities in patients surviving COVID-19.
Mild to moderate post-COVID-19 alters markers of lymphocyte activation, exhaustion, and immunometabolic responses that can be partially associated by physical activity level- an observational sub-analysis fit-COVID study
(2023) SILVA, Bruna Spolador de Alencar; PEREIRA, Telmo; MINUZZI, Luciele Guerra; PADILHA, Camila Souza; FIGUEIREDO, Caique; OLEAN-OLIVEIRA, Tiago; SANTOS, Ivete Vera Medeiros dos; MORANO, Ana Elisa von Ah; MARCHIOTO, Osmar; RIBEIRO, Jose Procopio Jabur; SANTOS, Vanessa Ribeiro Dos; SEELAENDER, Marilia; TEIXEIRA, Alexandre Abilio; SANTOS, Ronaldo Vagner T. Dos; LEMOS, Valdir de Aquino; FREIRE, Ana Paula Coelho Figueira; DORNELES, Gilson Pires; MARMETT, Bruna; OLEAN-OLIVEIRA, Andre; TEIXEIRA, Marcos F. S.; SERAPHIM, Patricia M.; CASEIRO, Armando; PINHO, Ricardo Aurino; ISLAM, Hashim; LITTLE, Jonathan Peter; KRUEGER, Karsten; ROSA-NETO, Jose Cesar; COELHO-E-SILVA, Manuel-Joao; LIRA, Fabio Santos
Aim: This study aimed to evaluate if physical activity is associated with systemic and cellular immunometabolic responses, in young adults after mild-to-moderate COVID-19 infection. Methods: Mild- to- moderate post-COVID-19 patients (70.50 +/- 43.10 days of diagnosis; age: 29.4 (21.9-34.9) years; BMI: 25.5 +/- 4.3 kg m(2) n = 20) and healthy age-matched controls (age: 29.3 (21.2 - 32.6) years; BMI: 25.4 +/- 4.7 kg m(2); n = 20) were evaluated. Physical activity levels (PAL), body composition, dietary habits, muscular and pulmonary function, mental health, sleep quality, metabolic parameters, immune phenotypic characterization, stimulated whole blood and PBMC culture (cytokine production), mRNA, and mitochondrial respiration in PBMCs were evaluated. Results: The post-COVID-19 group exhibited lower levels of moderate to vigorous physical activity (MVPA) (p = 0.038); therefore, all study comparisons were performed with adjustment for MVPA. Post-COVID-19 impacted the pulmonary function (FEV1, FEV1%pred, FVC, and FVC %pred) compared with the control (p adjusted by MVPA (p adj) <0.05). Post-COVID-19 exhibited lower levels of serum IL-6 (p adj <0.01), whereas it showed higher serum IL-10, triglyceride, leptin, IgG, ACE activity, TNFRSF1A, and PGE(2) (p adj <0.05) levels compared with controls. Post-COVID-19 presented a lower percentage of Treg cells (p adj = 0.03) and altered markers of lymphocyte activation and exhaustion (lower CD28 expression in CD8(+) T cells (p adj = 0.014), whereas CD4(+)T cells showed higher PD1 expression (p adj = 0.037)) compared with the control group. Finally, post- COVID-19 presented an increased LPS-stimulated whole- blood IL-10 concentration (p adj <0.01). When exploring mitochondrial respiration and gene expression in PBMCs, we observed a higher LEAK state value (p adj <0.01), lower OXPHOS activity (complex I) (p adj = 0.04), and expression of the Rev-Erb-alpha clock mRNA after LPS stimulation in the post-COVID-19 patients than in the control (p adj <0.01). Mainly, PAL was associated with changes in IL-10, triglyceride, and leptin levels in the plasma of post-COVID-19 patients. PAL was also associated with modulation of the peripheral frequency of Treg cells and the expression of PD-1 in CD8+ T cells, although it abrogated the statistical effect in the analysis of TNF-alpha and IL-6 production by LPS- and PMA-stimulated PBMC of post-COVID-19 patients. Conclusion: Young adults after mild-to-moderate SARS-CoV-2 infection appeared to have lower physical activity levels, which can be associated with clinical and immunometabolic responses in a complex manner.
The Effect of Gene Editing by CRISPR-Cas9 of miR-21 and the Indirect Target MMP9 in Metastatic Prostate Cancer
(2023) CAMARGO, Juliana A.; VIANA, Nayara I.; PIMENTA, Ruan; GUIMARAES, Vanessa R.; SANTOS, Gabriel A. dos; CANDIDO, Patricia; GHAZARIAN, Vitoria; ROMAO, Poliana; SILVA, Iran A.; BIRBRAIR, Alexander; SROUGI, Miguel; NAHAS, William C.; LEITE, Katia R.; TRARBACH, Ericka B.; REIS, Sabrina T.
Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.
Intracellular peptides in SARS-CoV-2-infected patients
(2023) MARTUCCI, Luiz Felipe; EICHLER, Rosangela A. S.; SILVA, Renee N. O.; COSTA, Tiago J.; TOSTES, Rita C.; BUSATTO, Geraldo F.; SEELAENDER, Marilia C. L.; DUARTE, Alberto J. S.; SOUZA, Heraldo P.; FERRO, Emer S.
Intracellular peptides (InPeps) generated by the orchestrated action of the proteasome and intracellular peptidases have biological and pharmacological sig-nificance. Here, human plasma relative concentration of specific InPeps was compared between 175 patients infected with severe acute respiratory syn-drome coronavirus 2 (SARS-CoV-2), and 45 SARS-CoV-2 non-infected patients; 2,466 unique peptides were identified, of which 67% were InPeps. The results re-vealed differences of a specific group of peptides in human plasma comparing non-infected individuals to patients infected by SARS-CoV-2, following the re-sults of the semi-quantitative analyses by isotope-labeled electrospray mass spectrometry. The protein-protein interactions networks enriched pathways, drawn by genes encoding the proteins from which the peptides originated, re-vealed the presence of the coronavirus disease/COVID-19 network solely in the group of patients fatally infected by SARS-CoV-2. Thus, modulation of the rela-tive plasma levels of specific InPeps could be employed as a predictive tool for disease outcome.
Role of Nutritional Supplements on Gut-Muscle Axis Across Age: a Mini-Review
(2023) NUCCI, Ricardo Aparecido Baptista; NEHMI FILHO, Victor Abou; JACOB-FILHO, Wilson; OTOCH, Jose Pinhata; PESSOA, Ana Flavia Marcal
Sarcopenia is a progressive skeletal muscle disorder associated with aging, resulting in loss of muscle mass and function. It has been linked to inflammation, oxidative stress, insulin resistance, hormonal changes (i.e. alterations in the levels or activity of hormones which can occur due to a variety of factors, including aging, stress, disease, medication, and environmental factors), and impaired muscle satellite cell activation. The gut microbiome is also essential for muscle health, and supplements such as probiotics, prebiotics, protein, creatine, and beta-alanine can support muscle growth and function while also promoting gut health. Chronic low-grade inflammation is a leading cause of sarcopenia, which can activate signaling pathways that lead to muscle wasting and reduce muscle protein synthesis. Insulin resistance, hormonal changes, and impaired muscle satellite cell activation contribute to sarcopenia, and high levels of fat mass also play a role in the pathogenesis of sarcopenia. Resistance exercise and dietary supplementation have been shown to be effective treatments for sarcopenia. In addition, a combination of resistance exercise and supplementation has been shown to have a more significant beneficial effect on anthropometric and muscle function parameters, leading to a decrease in sarcopenic state. Thus, understanding the relationship between the gut microbiome and muscle metabolism is crucial for developing new treatments for sarcopenia across age groups.
Cachexia causes time-dependent activation of the inflammasome in the liver
(2023) NEVES, Rodrigo Xavier das; YAMASHITA, Alex S.; RICCARDI, Daniela M. R.; KOHN-GAONE, Julia; CAMARGO, Rodolfo G.; NETO, Nelson I.; CAETANO, Daniela; GOMES, Silvio P.; SANTOS, Felipe H.; LIMA, Joanna D. C. C.; JR, Miguel L. Batista; ROSA-NETO, Jose Cesar; ALCANTARA, Paulo Sergio Martins De; MAXIMIANO, Linda F.; OTOCH, Jose P.; TRINCHIERI, Giorgio; TIRNITZ-PARKER, Janina E. E.; SEELAENDER, Marilia
BackgroundCachexia is a wasting syndrome associated with systemic inflammation and metabolic disruption. Detection of the early signs of the disease may contribute to the effective attenuation of associated symptoms. Despite playing a central role in the control of metabolism and inflammation, the liver has received little attention in cachexia. We previously described relevant disruption of metabolic pathways in the organ in an animal model of cachexia, and herein, we adopt the same model to investigate temporal onset of inflammation in the liver. The aim was thus to study inflammation in rodent liver in the well-characterized cachexia model of Walker 256 carcinosarcoma and, in addition, to describe inflammatory alterations in the liver of one cachectic colon cancer patient, as compared to one control and one weight-stable cancer patient. MethodsColon cancer patients (one weight stable [WSC] and one cachectic [CC]) and one patient undergoing surgery for cholelithiasis (control, n = 1) were enrolled in the study, after obtainment of fully informed consent. Eight-week-old male rats were subcutaneously inoculated with a Walker 256 carcinosarcoma cell suspension (2 x 10(7) cells in 1.0 mL; tumour-bearing [T]; or phosphate-buffered saline-controls [C]). The liver was excised on Days 0 (n = 5), 7 (n = 5) and 14 (n = 5) after tumour cell injection. ResultsIn rodent cachexia, we found progressively higher numbers of CD68(+) myeloid cells in the liver along cancer-cachexia development. Similar findings are described for CC, whose liver showed infiltration of the same cell type, compared with both WSC and control patient organs. In advanced rodent cachexia, hepatic phosphorylated c-Jun N-terminal kinase protein content and the inflammasome pathway protein expression were increased in relation to baseline (P < 0.05). These changes were accompanied by augmented expression of the active interleukin-1 beta (IL-1 beta) form (P < 0.05 for both circulating and hepatic content). ConclusionsThe results show that cancer cachexia is associated with an increase in the number of myeloid cells in rodent and human liver and with modulation of hepatic inflammasome pathway. The latter contributes to the aggravation of systemic inflammation, through increased release of IL-1 beta.

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