Artigos e Materiais de Revistas Científicas - LIM/05

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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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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.
Providing support to underprivileged people during the COVID-19 pandemic in Brazil: the role of the Trust Group and women leaders in São Paulo’s favelas
(2023) DOMINGOS, A. L. G.; MITKIEWICZ, J. M.; SALDIVA, P. H. N.
São Paulo was one of the epicenters of the COVID-19 pandemic in Brazil. Amongst underprivileged populations, such as slums residents, the impact of the pandemic was severe. This documentary reports the creation of the Trust Group, made up mostly of women community leaders in São Paulo’s slums, and how their actions inspired public policies in Brazil. Their lessons are examples of governance and solidarity in times of crisis and can serve as models for other cities in Latin America. The documentary describes this history as told by those community leaders. To watch the documentary, kindly visit the following link: https://youtu.be/61elJw0oqCY.
Locking and Unlocking Thrombin Function Using Immunoquiescent Nucleic Acid Nanoparticles with Regulated Retention In Vivo
(2022) KE, W.; CHANDLER, M.; CEDRONE, E.; SAITO, R. F.; RANGEL, M. C.; JUNQUEIRA, M. De Souza; WANG, J.; SHI, D.; TRUONG, N.; RICHARDSON, M.; ROLBAND, L. A.; DRéAU, D.; BEDOCS, P.; CHAMMAS, R.; DOKHOLYAN, N. V.; DOBROVOLSKAIA, M. A.; AFONIN, K. A.
The unbalanced coagulation of blood is a life-threatening event that requires accurate and timely treatment. We introduce a user-friendly biomolecular platform based on modular RNA-DNA anticoagulant fibers programmed for reversible extracellular communication with thrombin and subsequent control of anticoagulation via a ""kill-switch""mechanism that restores hemostasis. To demonstrate the potential of this reconfigurable technology, we designed and tested a set of anticoagulant fibers that carry different thrombin-binding aptamers. All fibers are immunoquiescent, as confirmed in freshly collected human peripheral blood mononuclear cells. To assess interindividual variability, the anticoagulation is confirmed in the blood of human donors from the U.S. and Brazil. The anticoagulant fibers reveal superior anticoagulant activity and prolonged renal clearance in vivo in comparison to free aptamers. Finally, we confirm the efficacy of the ""kill-switch""mechanism in vivo in murine and porcine models.
Engaging stakeholders to level up COPD care in LMICs: lessons learned from the ""Breathe Well"" programme in Brazil, China, Georgia, and North Macedonia
(2024) FERNANDES, Genevie; WILLIAMS, Sian; ADAB, Peymane; GALE, Nicola; JONG, Corina de; SOUSA, Jaime Correia de; CHENG, Kk; CHI, Chunhua; COOPER, Brendan G.; DICKENS, Andrew P.; ENOCSON, Alexandra; FARLEY, Amanda; JOLLY, Kate; JOWETT, Sue; MAGLAKELIDZE, Maka; MAGHLAKELIDZE, Tamaz; MARTINS, Sonia; SITCH, Alice; STAMENOVA, Aleksandra; STAVRIKJ, Katarina; STELMACH, Rafael; TURNER, Alice; PAN, Zihan; PANG, Hui; ZHANG, Jianxin; JORDAN, Rachel E.
BackgroundEffective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned.Main bodyEach country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice.ConclusionStakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.
Changes after 12 years of follow-up severe asthma patients cohort: higher obstruction and comorbidities, but significant better quality of life
(2023) JR, N. G. Santos; LIMA, R. M.; ATHANAZIO, R. A.; PINTO, R. M. Carvalho; RABE, K.; CUKIER, A.; STELMACH, R.
Background The Brazilian Cohort of Asthma Sao Paulo (BRASASP) had a well-characterized severe asthmatic in Brazil, with 12 years of follow-up under standard treatment. Methods Sequential assessment of patients with uncontrolled asthma from BRASASP cohort was carried out with 12 years of follow-up, performing exams and comparing with previous measurements. Results 50 from the 60 initial patients were reevaluated. Twelve years later, FEV1 and the FEV1/FVC ratio have significantly decreased, with a rate of loss of lung function of 11.8 and 14%, respectively, and worsening in small airway parameters such as RV/TLC. BMI, The Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) scores haven't changed. However, exacerbations decreased by 56%. Mean daily inhaled corticosteroid use was similar over time, but daily oral corticosteroid use decreased, in addition to a significant reduction in induced sputum eosinophilic and neutrophilic profile and serum IgE. Rhinitis, sinusitis, and GERD were the main comorbidities. In quality of life according to respiratory questionnaire SGRQ, total score showed a huge improvement (62% of patients). Conclusions There was significant decrease in FEV1 and FEV1/FVC. Data of pulmonary functional small airway characteristics show globally affected airways. Although higher doses of medications, patients were still uncontrolled, but with reduction of exacerbations, daily use of oral corticosteroid, less eosinophils and neutrophils in induced sputum and lower levels of IgE. Improvement in quality of life in 62% of patients.
Ultrasonography on the non-living. Current approaches.
(2023) THOMSEN, Thomas; BLAIVAS, Michael; SADIVA, Paulo; KRIPFGANS, Oliver D.; CHAN, Hsun-Liang; DONG, Yi; CHAMMAS, Maria Cristina; HOFFMANN, Beatrice; DIETRICH, Christoph F.
The vast majority of clinicians associate diagnostic ultrasound with a tool that is designed for the living patient. However, it is of course possible to apply this imaging technology to evaluate the recently deceased patient for postmortem diagnosis, or even just examine postmortem tissue. We describe several cases in which ultrasound-enabled providers obtain answers in postmortem examinations and discuss potential future strategies and applications. In addition, we will also illustrate the use of sonography in minimally invasive post-mortem tissue sampling (MITS), an approach that can be used in post-mortem minimally invasive autopsies as well as for establishing ultrasound diagnostic parameters in new medical fields such as periodontal and dental implant specialties.
COVID-19: detection methods in post-mortem samples
(2023) TEDESCO, Ilaria; MARINO, Federica Zito; RONCHI, Andrea; NETO, Amaro Nunes Duarte; DOLHNIKOFF, Marisa; MUNICINO, Maurizio; CAMPOBASSO, Carlo Pietro; PANNONE, Giuseppe; FRANCO, Renato
COVID-19 identification is routinely performed on fresh samples, such as nasopharyngeal and oropharyngeal swabs, even if, the detection of the virus in formalin-fixed paraffinembedded (FFPE) autopsy tissues could help to underlie mechanisms of the pathogenesis that are not well understood. The gold standard for COVID-19 detection in FFPE samples remains the qRT-PCR as in swab samples, contextually other methods have been developed, including immunohistochemistry (IHC), and in situ hybridization (ISH). In this manuscript, we summarize the main data regarding the methods of COVID-19 detection in pulmonary and extra-pulmonary post-mortem samples, and especially the sensitivity and specificity of these assays will be discussed.
miRNA-143 expression is associated with inflammation and time of exposure to amniotic fluid in experimental gastroschisis
(2023) DINIZ, Ana Maria Bicudo; GUALBERTO, Igor Jose Nogueira; LIMA, Luiza Almeida; CIRINO, Mucio Luiz de Assis; MURAKAMI, Rodrigo Kendi; ISHIKIRIAMA, Bella Luna Colombini; RUANO, Rodrigo; SILVA, Luiz Fernando Ferraz da; TIRAPELLI, Daniela; SBRAGIA, Loureneo
Objective: Gastroschisis (GS) is a congenital anomaly in the abdominal wall with the intestinal loops exiting laterally to the umbilicus. The contact of the loops with Amniotic Fluid (AF) causes an inflammatory process in the exposed part, leading to an extended hospital stay and an increased risk of morbidity due to alterations related to intestinal motility. The authors aimed to evaluate the time of exposure to the AF in the experimental GS and to search for potential biomarkers of intestinal inflammation by measuring microRNAs.Methods: Rat fetuses were divided into three groups: a) CONTROL, b) GS reared on day 18 (GS = 18), and c) GS reared on day 19.5 (GS = 19) (term = 22 days). On day 21.5, the fetuses were removed for biometric parameters and biochemical analyses: 1) Biometrics: Body and Intestinal Weight (BW, IW), and intestinal-body weight ratio (IW/ BW); 2) Descriptive histopathology and 3) miR-143 quantification by real-time Polymerase Chain Reaction (PCR).Results: BW was higher in CONTROL than GS 18 and G19 (p < 0.05). IW, IW/BW, intestinal water, and mRNA-143 were higher in GS 18 and GS 19 than in CONTROL, and GS 18 was higher than GS 19 (p < 0.05). The average of the inflammation score from the intestinal wall with mucosal inflammation and intra-epithelial lymphocytes shows worst in GS 18 and GS 19 vs. CONTROL (p < 0.05).Conclusions: The tissue expression of mRNA-143 and the morphological changes in the intestine of GS worsened according to the time of exposure to AF, which could be a possible marker of fetal intestinal damage.
Mental health among children and adolescents after SARS-CoV-2 infection: A prospective study in a tertiary university hospital
(2023) MATSUO, Olivia Mari; LINDOSO, Livia; MARQUES, Heloisa Helena de Sousa; V, Guilherme Polanczyk; FARHAT, Sylvia Costa Lima; BAIN, Vera; FINK, Thais T.; MARTINS, Fernanda; ASTLEY, Camilla; SUGUITA, Priscila; TRINDADE, Vitor; CORREA-SILVA, Simone; PALMEIRA, Patricia; SANSON, Camila; PAULA, Yoshino de; LITVINOV, Nadia; FERREIRA, Juliana Caires O. A.; SAKITA, Neusa Keico; GUALANO, Bruno; SILVA, Clovis Artur A.; PEREIRA, Maria Fernanda Badue
A novel program of infiltrative control in astrocytomas: ADAM23 depletion promotes cell invasion by activating γ-secretase complex
(2023) JANDREY, Elisa Helena Farias; BARNABE, Gabriela Filoso; MALDAUN, Marcos; ASPRINO, Paula Fontes; SANTOS, Natalia Cristina dos; INOUE, Lilian Tiemi; ROZANSKI, Andrei; GALANTE, Pedro Alexandre Favoretto; MARIE, Suely Kazue Nagahashi; OBA-SHINJO, Sueli Mieko; SANTOS, Tiago Goss dos; CHAMMAS, Roger; LANCELLOTTI, Carmen Lucia Penteado; FURNARI, Frank B.; CAMARGO, Anamaria Aranha; COSTA, Erico Tosoni
Background. Infiltration is a life-threatening growth pattern in malignant astrocytomas and a significant cause of therapy resistance. It results in the tumor cell spreading deeply into the surrounding brain tissue, fostering tumor recurrence and making complete surgical resection impossible. We need to thoroughly understand the mechanisms underlying diffuse infiltration to develop effective therapies.Methods We integrated in vitro and in vivo functional assays, RNA sequencing, clinical, and expression information from public data sets to investigate the role of ADAM23 expression coupling astrocytoma's growth and motility.Results. ADAM23 downregulation resulted in increased infiltration, reduced tumor growth, and improved overall survival in astrocytomas. Additionally, we show that ADAM23 deficiency induces gamma-secretase (GS) complex activity, contributing to the production and deposition of the Amyloid-beta and release of NICD. Finally, GS ablation in ADAM23-low astrocytomas induced a significant inhibitory effect on the invasive programs.Conclusions. Our findings reveal a role for ADAM23 in regulating the balance between cell proliferation and invasiveness in astrocytoma cells, proposing GS inhibition as a therapeutic option in ADAM23 low-expressing astrocytomas.
Intranasal Liposomal Formulation of Spike Protein Adjuvanted with CpG Protects and Boosts Heterologous Immunity of hACE2 Transgenic Mice to SARS-CoV-2 Infection
(2023) RUSSO, Momtchilo; MENDES-CORREA, Maria Cassia; LINS, Bruna B.; KERSTEN, Victor; PERNAMBUCO, Paulo C. A.; MARTINS, Toni Ricardo; TOZETTO-MENDOZA, Tania Regina; BOAS, Lucy Santos Vilas; GOMES, Brisa Moreira; DATI, Livia Mendonca Munhoz; DUARTE-NETO, Amaro Nunes; REIGADO, Gustavo Roncoli; FREDERICO, Ana Beatriz T.; CUNHA, Danielle R. de A.; PAULA, Anderson Vicente de; SILVA, Jose Igor G. da; VASCONCELOS, Carlos F. Moreira; CHAMBERGO, Felipe S.; NUNES, Viviane Abreu; BOM, Ana Paula Dinis Ano; CASTILHO, Leda R.; MARTINS, Rodrigo A. P.; HIRATA, Mario Hiroyuki; MIROTTI, Luciana; TRIPP, Ralph A.
Mucosal vaccination appears to be suitable to protect against SARS-CoV-2 infection. In this study, we tested an intranasal mucosal vaccine candidate for COVID-19 that consisted of a cationic liposome containing a trimeric SARS-CoV-2 spike protein and CpG-ODNs, a Toll-like receptor 9 agonist, as an adjuvant. In vitro and in vivo experiments indicated the absence of toxicity following the intranasal administration of this vaccine formulation. First, we found that subcutaneous or intranasal vaccination protected hACE-2 transgenic mice from infection with the wild-type (Wuhan) SARS-CoV-2 strain, as shown by weight loss and mortality indicators. However, when compared with subcutaneous administration, the intranasal route was more effective in the pulmonary clearance of the virus and induced higher neutralizing antibodies and anti-S IgA titers. In addition, the intranasal vaccination afforded protection against gamma, delta, and omicron virus variants of concern. Furthermore, the intranasal vaccine formulation was superior to intramuscular vaccination with a recombinant, replication-deficient chimpanzee adenovirus vector encoding the SARS-CoV-2 spike glycoprotein (Oxford/AstraZeneca) in terms of virus lung clearance and production of neutralizing antibodies in serum and bronchial alveolar lavage (BAL). Finally, the intranasal liposomal formulation boosted heterologous immunity induced by previous intramuscular vaccination with the Oxford/AstraZeneca vaccine, which was more robust than homologous immunity.
Association between illness perception and clinical control, quality of life, physical activity, and psychosocial status in subjects with moderate to severe asthma: a cluster analysis
(2023) SILVA, Simone T. Camargo; FREITAS, Patricia Duarte; LUNARDI, Adriana Claudia; XAVIER, Rafaella Fagundes; BARBOSA, Renata Cleia C.; STELMACH, Rafael; CARVALHO, Celso R. F.
Background: Illness perception (IP) is a psychosocial factor involved in several chronic diseases and is associated with relevant clinical outcomes. However, the relationship between IP and health-related quality of life (HRQoL), psychosocial status, and physical activity in daily life (PADL) in subjects with asthma is poorly understood.Objective: To identify groups of subjects with asthma based on their IPs and to assess their association with clinical control, HRQoL, psychosocial disturbances, and PADL.Methods: This cross-sectional study included 149 subjects with moderate to severe asthma. IP, anthropometric data, Asthma Control Questionnaire-7, Asthma Quality of Life Questionnaire, Hospital Anxiety and Depression Scale, PADL (accelerometry), and general self-efficacy (GSE) were assessed. Cluster analysis was performed to identify clusters with similar profiles and investigate their characteristics and differences. Pearson's correlation coefficient was used to test the associations between IP and other variables.Results: Statistical analyses identified two clusters of subjects with asthma based on IP. Cluster 1 presented worse IP in seven out of eight domains than Cluster 2. Cluster 1 had more negative consequences of the disease, worse understanding, and a high emotional representation of the disease than Cluster 2. Cluster 1 also had a greater extent of asthma symptoms, poor clinical control, worse HRQoL, and more symptoms of anxiety and depression. No difference between clusters was found for PADL or self-efficacy.Conclusion: Subjects with asthma who have worse IP have more negative symptoms, worse clinical control, HRQoL, and symptoms of anxiety and depression.
Elastic tape reduces dyspnea and improves health status in the short term in nonobese COPD males: A randomized controlled trial
(2024) SANTOS, Eloise Arruda dos; PINTO, Thiago Fernandes; XAVIER, Rafaella Fagundes; STELMACH, Rafael; CARVALHO-PINTO, Regina Maria; CARVALHO, Celso Ricardo Fernandes de
Introduction and objectives: The elastic tape (ET) is a novel intervention that acutely improves exercise capacity in laboratory tests; however, its effect on a patient's daily life remains unknown. This randomized controlled trial evaluated the effects of ET on daily life physical activity (DLPA), dyspnea symptoms, health status, and health -related quality of life (HRQoL) in individuals with COPD. Methods: Fifty males with moderate to very severe COPD were randomly assigned to an intervention group (ETG, n = 25), receiving ET on the chest wall and abdomen, or a control group (CG, n = 25). The intervention was for 14 days. DLPA (accelerometry; steps per day, and sedentary time), dyspnea symptoms (transition dyspnea index, TDI; and modified Medical Research Council, mMRC), health status (COPD assessment test, CAT), and health -related quality of life (HRQoL, CRQ) were evaluated at baseline and on Day 21 after the intervention. Results: No change in the DLPA was observed in between-group comparison. CG presented a reduction in step counts after 21days (-707,p <0.05) while ETG. maintained (-114,p > 0.94). However, ET reduced dyspnea symptoms in all TDI domains (functional, task, and effort) and on the mMRC scale after 14 days compared with CG (p < 0.01). Also, the ETG improved CAT score compared to the CG, reaching minimal clinical important difference (MCID) (-4.4 score, p <0.01). The ETG also improved in most CRQ domains reaching MCID after 21 days. Conclusions: ET does not modify DLPA but reduces dyspnea and improves health status and HRQoL in nonobese males with moderate to very severe COPD in the short term. This novel and low-cost intervention improves COPD symptoms.
Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression
(2023) TOBIAS, Gabriel C.; GOMES, Joao L. P.; FERNANDES, Larissa G.; VOLTARELLI, Vanessa A.; ALMEIDA, Ney R. de; JANNIG, Paulo R.; SOUZA, Rodrigo W. Alves de; NEGRAO, Carlos E.; OLIVEIRA, Edilamar M.; CHAMMAS, Roger; ALVES, Christiano R. R.; BRUM, Patricia C.
Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.
Small airways morphological alterations associated with functional impairment in lymphangioleiomyomatosis
(2024) MENDONCA, Ligia Pelosi; COSTA, Natalia de Souza Xavier; NASCIMENTO, Ellen Caroline Toledo do; OLIVEIRA, Martina Rodrigues de; CARVALHO, Carlos Roberto Ribeiro de; BALDI, Bruno Guedes; DOLHNIKOFF, Marisa
BackgroundLymphangioleiomyomatosis (LAM) is a rare neoplastic and cystic pulmonary disease characterized by abnormal proliferation of the so-called LAM cells. Despite the functional obstructive pattern observed in most patients, few studies investigated the morphological changes in the small airways, most of them in patients with severe and advanced LAM undergoing lung transplantation. Understanding the morphological changes in the airways that may occur early in the disease can help us understand the pathophysiology of disease progression and understand the rationale for possible therapeutic approaches, such as the use of bronchodilators. Our study aimed to characterize the morphological alterations of the small airways in patients with LAM with different severities compared to controls, and their association with variables at the pulmonary function test and with LAM Histological Score (LHS).MethodsThirty-nine women with LAM who had undergone open lung biopsy or lung transplantation, and nine controls were evaluated. The histological severity of the disease was assessed as LHS, based on the percentage of tissue involvement by cysts and infiltration by LAM cells. The following morphometric parameters were obtained: airway thickness, airway closure index, collagen and airway smooth muscle content, airway epithelial TGF-beta expression, and infiltration of LAM cells and inflammatory cells within the small airway walls.ResultsThe age of patients with LAM was 39 +/- 8 years, with FEV1 and DLCO of 62 +/- 30% predicted and 62 +/- 32% predicted, respectively. Patients with LAM had increased small airway closure index, collagen and smooth muscle content, and epithelial TGF-beta expression compared with controls. Patients with LAM with the more severe LHS and with greater functional severity (FEV1 <= 30%) presented higher thicknesses of the airways. Bronchiolar inflammation was mild; infiltration of the small airway walls by LAM cells was rare. LHS was associated with an obstructive pattern, air trapping, and reduced DLCO, whereas small airway wall thickness was associated with FEV1, FVC, and collagen content.ConclusionLAM is associated with small airway remodelling and partial airway closure, with structural alterations observed at different airway compartments. Functional impairment in LAM is associated with airway remodelling and, most importantly, with histological severity (LHS).
Neurovascular and hemodynamic responses to mental stress and exercise in severe COVID-19 survivors
(2023) FARIA, Diego; MOLL-BERNARDES, Renata; TESTA, Laura; MONIZ, Camila M. V.; RODRIGUES, Erika C.; MOTA, Jose M.; SOUZA, Francis R.; ALVES, Maria Janieire N. N.; ONO, Bruna E.; IZAIAS, Joao E.; SALES, Artur O.; RODRIGUES, Thais S.; SALEMI, Vera M. C.; JORDAO, Camila P.; ANGELIS, Katia De; CRAIGHEAD, Daniel H.; ROSSMAN, Matthew J.; BORTOLOTTO, Luiz A.; CONSOLIM-COLOMBO, Fernanda M.; IRIGOYEN, Maria C. C.; SEALS, Douglas R.; NEGRAO, Carlos E.; SALES, Allan R. K.
Previous studies show that COVID-19 survivors have elevated muscle sympathetic nerve activity (MSNA), endothelial dysfunction, and aortic stiffening. However, the neurovascular responses to mental stress and exercise are still unexplored. We hypothesized that COVID-19 survivors, compared with age-and body mass index (BMI)-matched control subjects, exhibit abnormal neurovascular responses to mental stress and physical exercise. Fifteen severe COVID-19 survivors (aged: 49 +/- 2 yr, BMI: 30 +/- 1 kg/m(2)) and 15 well-matched control subjects (aged: 46 +/- 3 yr, BMI: 29 +/- 1 kg/m(2)) were studied. MSNA (microneurography), forearm blood flow (FBF), and forearm vascular conductance (FVC, venous occlusion plethysmography), mean arterial pressure (MAP, Finometer), and heart rate (HR, ECG) were measured during a 3-min mental stress (Stroop Color-Word Test) and during a 3-min isometric handgrip exercise (30% of maximal voluntary contraction). During mental stress, MSNA (frequency and incidence) responses were higher in COVID-19 survivors than in controls (P < 0.001), and FBF and FVC responses were attenuated (P < 0.05). MAP was similar between the groups (P > 0.05). In contrast, the MSNA (frequency and incidence) and FBF and FVC responses to handgrip exercise were similar between the groups (P > 0.05). MAP was lower in COVID-19 survivors (P < 0.05). COVID-19 survivors exhibit an exaggerated MSNA and blunted vasodilatory response to mental challenge compared with healthy adults. However, the neurovascular response to handgrip exercise is preserved in COVID-19 survivors. Overall, the abnormal neurovascular control in response to mental stress suggests that COVID-19 survivors may have an increased risk to cardiovascular events during mental challenge.
Detection of unreported usage of the antiretroviral drug lamivudine in two blood donors
(2023) NISHIYA, Anna; SALLES, Nanci; ALMEIDA-NETO, Cesar de; FERREIRA, Suzete; NOGUEIRA, Fatima; ROCHA, Vanderson; MENDRONE, Alfredo
Background Unreported HIV antiretroviral (ARV) drug usage by blood donors compromises the ability to detect evidence of HIV infection in blood screening tests and represents a risk for blood transfusion safety. Our objective was to determine the frequency of undeclared ARV drug use by blood donors with altered HIV markers.Study Design and Methods This was a retrospective cross-sectional analysis of donations that were tested for HIV antibody (ab), antigen (ag), and RNA by chemiluminescent immunoassay and nucleic acid screening tests. Positive samples were retested and were subjected to ARV drug testing by high-performance liquid chromatography-tandem mass spectrometry.Results Of 345,252 blood donations, 361 (0.1%) were positive on initial testing. Samples from 296 (81.9%) of these donations were available for further analysis. The presence of HIV ab/ag and/or RNA was confirmed in 83 (28.0%) of these samples. All 296 bloods were subjected to ARV testing. The ARV drug lamivudine, at 11.3 and 6.7 ng/mL, was detected in 2 of 83 (2.4%) donations that were HIV positive. Other drugs were not detected.Conclusion Unreported ARV usage was identified in two candidates for blood donation. More intensive efforts to educate donors about disclosure and to investigate the extent of this phenomenon in Brazil are needed.
Randomised controlled trial testing effectiveness of feedback about lung age or exhaled CO combined with very brief advice for smoking cessation compared to very brief advice alone in North Macedonia: findings from the Breathe Well group
(2023) GJORGJIEVSKI, Dragan; STAVRIKJ, Katarina; JORDAN, Rachel; ADAB, Peymane; STANOEVSKI, Gjorgji; STAMENOVA, Aleksandra; KRSTEVSKA, Emilija; SIMONOVSKA, Sara; TRPCHESKI, Fillip; ADAMS, Rachel; EASTER, Christina; RAI, Kiran; CHENG, Kar Keung; CHI, Chunhua; COOPER, Brendan G.; CORREIA-DE-SOUSA, Jaime; DICKENS, Andrew P.; ENOCSON, Alexandra; GALE, Nicola; JOLLY, Kate; JOWETT, Sue; MAGLAKELIDZE, Mariam; MAGHLAKELIDZE, Tamaz; MARTINS, Sonia; SITCH, Alice; STELMACH, Rafael; TURNER, Alice; WILLIAMS, Sian; FARLEY, Amanda
IntroductionIn 2019, smoking prevalence in North Macedonia was one of the world's highest at around 46% in adults. However, access to smoking cessation treatment is limited and no co-ordinated smoking cessation programmes are provided in primary care.MethodsWe conducted a three parallel-armed randomised controlled trial (n = 1368) to investigate effectiveness and cost-effectiveness of lung age (LA) or exhaled carbon monoxide (CO) feedback combined with very brief advice (VBA) to prompt smoking cessation compared with VBA alone, delivered by GPs in primary care in North Macedonia. All participants who decided to attempt to quit smoking were advised about accessing smoking cessation medications and were also offered behavioural support as part of the ""ACT"" component of VBA. Participants were aged >= 35 years, smoked >= 10 cigarettes per day, were recruited from 31 GP practices regardless of motivation to quit and were randomised (1:1:1) using a sequence generated before the start of recruitment. The primary outcome was biochemically validated 7-day point prevalence abstinence at 4 weeks (wks). Participants and GPs were not blinded to allocation after randomisation, however outcome assessors were blind to treatment allocation.ResultsThere was no evidence of a difference in biochemically confirmed quitting between intervention and control at 4wks (VBA + LA RR 0.90 (97.5%CI: 0.35, 2.27); VBA + CO RR 1.04 (97.5%CI: 0.44, 2.44)), however the absolute number of quitters was small (VBA + LA 1.6%, VBA + CO 1.8%, VBA 1.8%). A similar lack of effect was observed at 12 and 26wks, apart from in the VBA + LA arm where the point estimate was significant but the confidence intervals were very wide. In both treatment arms, a larger proportion reported a reduction in cigarettes smoked per day at 4wks (VBA + LA 1.30 (1.10, 1.54); VBA + CO 1.23 (1.03, 1.49)) compared with VBA. The point estimates indicated a similar direction of effect at 12wks and 26wks, but differences were not statistically significant. Quantitative process measures indicated high fidelity to the intervention delivery protocols, but low uptake of behavioural and pharmacological support. VBA was the dominant intervention in the health economic analyses.ConclusionOverall, there was no evidence that adding LA or CO to VBA increased quit rates. However, a small effect cannot be ruled out as the proportion quitting was low and therefore estimates were imprecise. There was some evidence that participants in the intervention arms were more likely to reduce the amount smoked, at least in the short term. More research is needed to find effective ways to support quitting in settings like North Macedonia where a strong smoking culture persists.Trial registrationThe trial was registered at http://www.isrctn.com (ISRCTN54228638) on the 07/09/2018.
Effect of aerobic and resistance exercise training on endothelial function in individuals with overweight and obesity: a systematic review with meta-analysis of randomized clinical trials
(2023) CORTES, Maiquel Bueno; SILVA, Raphael Silveira Nunes da; OLIVEIRA, Patricia Caetano de; SILVA, Diego Silveira da; IRIGOYEN, Maria Claudia Costa; WACLAWOVSKY, Gustavo; SCHAUN, Maximiliano Isoppo
The objective of this systematic review was to examine the effects of exercise training on endothelial function in individuals with overweight and obesity. Our review study included only randomized controlled trials (RCTs) involving adults (>= 18 years of age) with body mass index (BMI)>= 25.0 kg/m(2). Our search was conducted in the electronic bases MEDLINE (PubMed), Cochrane, LILACS and EMBASE and in the gray literature. We performed random-effects analyses for effect estimates and used 95% prediction intervals (95% PI) for estimating the uncertainty of the study results. There were selected 10 RCTs involving 14 groups (n=400). The quality assessment of studies using Cochrane risk-of-bias 2 (RoB 2) tool identified some concerns. Exercise training resulted in improved flow-mediated dilation (FMD) in individuals with overweight and obesity (p<0.001) compared to the no-exercise control group. This effect of training modalities on FMD was seen for aerobic training (p<0.001) but not for resistance training (p=0.051). There was no difference in FMD in response to exercise training by BMI classification (overweight, obesity, overweight+obesity), p=0.793. The present results are consistent with the notion that aerobic exercise training elicits favorable adaptations in endothelial function in individuals with overweight and obesity. Our findings should be interpreted with caution because of the small number of studies included in this review.
Fast and cost-effective protocol to produce Paracoccidioides spp. antigens
(2023) FERNANDES-BERALDO, Karolina Rosa; FREITAS-XAVIER, Roseli Santos de; PARDINI-VICENTINI, Adriana
Introduction. The existing methods for Paracoccidioides spp. antigen production are problematic in terms of standardization, specificity, stability, repeatability, and reproducibility.Objective. To optimize the methodology for Paracoccidioides spp. antigen production and evaluate its applicability in paracoccidioidomycosis immunodiagnosis.Materials and methods. The antigens were obtained from Paracoccidioides lutzii isolates (01, 66, and 8334), Paracoccidioides brasiliensis sensu stricto (113), and Paracoccidioides restripiensis (B-339). These fungi were grown at 36 degrees C +/- 1 degrees C, on modified Fava-Netto agar, according to Freitas et al. (2018). Paracoccidioides lutzii antigens were obtained after 5, 10, and 20 days of culture, whereas P. brasiliensis and P. restripiensis antigens were obtained after 10 days. Antigens were evaluated in natura, 10 and 20 times concentrated. Antigenic capacity was evaluated using a double immunodiffusion assay against serum samples from patients with paracoccidioidomycosis, histoplasmosis, and aspergillosis, and random blood donors.Results. Cross-reactivity between Paracoccidioides spp. antigens was observed when P. brasiliensis, P. restrepiensis antigens, and P. lutzii antigens were evaluated with the polyclonal antibodies against P. lutzii and P. brasiliensis, respectively. No cross-reactivity was obtained for polyclonal antibodies against Histoplasma capsulatum, Aspergillus fumigatus, and random blood donors. The proposed protocol allowed stable, repeatable, and reproducible genus-specific antigen production at a low cost and in a short cultivation time.Conclusion. The proposed protocol allowed us to obtain genus-specific antigens that can be developed and reproduced in all laboratories in Brazil and South America, where paracoccidioidomycosis is a neglected disease, contributing to an early diagnosis, especially in endemic regions, regardless of the species.

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