Molecular and cellular biomarkers of COVID-19 prognosis : protocol for the prospective cohort TARGET study

Background: Since the beginning of the COVID-19 pandemic, the world’s attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. Objective: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. Methods: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction–confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. Results: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase

Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil

The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Antitumor and immunomodulatory activities of thiosemicarbazones and 1,3-Thiazoles in Jurkat and HT-29 cells

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-29T13:13:53Z No. of bitstreams: 1 Santos TAR Antitumor and immunomodulatory....pdf: 770132 bytes, checksum: b6d055670f9e6f1821da4d2895ab7c0d (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-29T13:24:03Z (GMT) No. of bitstreams: 1 Santos TAR Antitumor and immunomodulatory....pdf: 770132 bytes, checksum: b6d055670f9e6f1821da4d2895ab7c0d (MD5)Made available in DSpace on 2016-12-29T13:24:03Z (GMT). No. of bitstreams: 1 Santos TAR Antitumor and immunomodulatory....pdf: 770132 bytes, checksum: b6d055670f9e6f1821da4d2895ab7c0d (MD5) Previous issue date: 2016Brazilian National Research Council (CNPq), Research Foundation of Pernambuco State (FACEPE) and FIOCRUZ.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunogenética. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunogenética. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunogenética. Recife, PE, BrasilCancer remains a high incidence and mortality disease, causing around 8.2 million of deaths in the last year. Current chemotherapy needs to be expanded, making research for new drugs a necessary task. Immune system modulation is an emerging concept in cancer cell proliferation control. In fact, there are a number of mechanisms underlying the role immune system plays in tumor cells. In this work, we describe the structural design, synthesis, antitumor and immunomodulatory potential of 31 new 1,3-thiazole and thiosemicarbazone compounds. Cisplatin was used as anticancer drug control. Cytotoxicity against J774A.1 macrophages and antitumor activity against HT-29 and Jurkat cells was determined. These 1,3-thiazole and thiosemicarbazone compounds not only exhibited cytotoxicity in cancer cells, but were able to cause irreversible cancer cell damage by inducing necrosis and apoptosis. In addition, these compounds, especially pyridyl-thiazoles compounds, regulated immune factors such as interleukin 10 and tumor necrosis factor, possible by directing immune system in favor of modulating cancer cell proliferation. By examining their pharmacological activity, we were able to identify new potent and selective anticancer compounds

Conformational restriction of aryl thiosemicarbazones produces potent and selective anti-Trypanosoma cruzi compounds which induce apoptotic parasite death

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-23T17:44:38Z No. of bitstreams: 1 Moreira DRM Conformational restriction....pdf: 1062616 bytes, checksum: 2f9250256b9569bd49a2a776fd0360cb (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-23T18:13:22Z (GMT) No. of bitstreams: 1 Moreira DRM Conformational restriction....pdf: 1062616 bytes, checksum: 2f9250256b9569bd49a2a776fd0360cb (MD5)Made available in DSpace on 2018-04-23T18:13:22Z (GMT). No. of bitstreams: 1 Moreira DRM Conformational restriction....pdf: 1062616 bytes, checksum: 2f9250256b9569bd49a2a776fd0360cb (MD5) Previous issue date: 2014CNPq (grant 471461/2011-3 to A.C.L.L. and 477435/2012-2 to R.S.F.) and FACEPEFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade de São Paulo. Instituto de Física de São Carlos. São Carlos, SP, BrasilUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilChagas disease, caused by Trypanosoma cruzi, is a life-threatening infection leading to approximately 12,000 deaths per year. T. cruzi is susceptible to thiosemicarbazones, making this class of compounds appealing for drug development. Previously, the homologation of aryl thiosemicarbazones resulted in an increase in anti-T. cruzi activity in comparison to aryl thiosemicarbazones without a spacer group. Here, we report the structural planning, synthesis and anti-T. cruzi evaluation of new aryl thiosemicarbazones (9a-x), designed as more conformationally restricted compounds. By varying substituents attached to the phenyl ring, substituents were observed to retain, enhance or greatly increase the anti-T. cruzi activity, in comparison to the nonsubstituted derivative. In most cases, hydrophobic and bulky substituents, such as bromo, biphenyl and phenoxyl groups, greatly increased antiparasitic activity. Specifically, thiosemicarbazones were identified that inhibit the epimastigote proliferation and were toxic for trypomastigotes without affecting mouse splenocytes viability. The most potent anti-T. cruzi thiosemicarbazones were evaluated against cruzain. However, inhibition of this enzyme was not observed, suggesting that the compounds work through another mechanism. In addition, examination of T. cruzi cell death showed that these thiosemicarbazones induce apoptosis. In conclusion, the structural design executed within the series of aryl thiosemicarbazones (9a-x) led to the identification of new potent anti-T. cruzi agents, such as compounds (9h) and (9r), which greatly inhibited epimastigote proliferation, and demonstrated a toxicity for trypomastigotes, but not for splenocytes. Mechanistically, these compounds do not inhibit the cruzain, but induce T. cruzi cell death by an apoptotic process

New 1,3-thiazole derivatives and their biological and ultrastructural effects on Trypanosoma cruzi

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-13T14:26:25Z No. of bitstreams: 1 Gomes PATM New 1,3-thiazole derivatives....pdf: 2013088 bytes, checksum: 8ca722694d65ed4ac9b209d95a69248c (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-13T16:21:46Z (GMT) No. of bitstreams: 1 Gomes PATM New 1,3-thiazole derivatives....pdf: 2013088 bytes, checksum: 8ca722694d65ed4ac9b209d95a69248c (MD5)Made available in DSpace on 2016-12-13T16:21:46Z (GMT). No. of bitstreams: 1 Gomes PATM New 1,3-thiazole derivatives....pdf: 2013088 bytes, checksum: 8ca722694d65ed4ac9b209d95a69248c (MD5) Previous issue date: 2016CNPq; CAPES; PRONEX-FAPESB; PRONEM/FACEPE/CNPq.Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade de Pernambuco. Petrolina, PE, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilMinistry of Education of Brazil. CAPES Foundation. Brasília, DF, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilIn previous studies, the compound 3-(bromopropiophenone) thiosemicarbazone was described as a potent anti-Trypanosoma cruzi and cruzain inhibitor. In view to optimize this activity, 1,3-thiazole core was used as building-block strategy to access new lead generation of anti T. cruzi agents. In this way a series of thiazole derivatives were synthesized and most of these derivatives exhibited antiparasitic activity similar to benznidazole (Bzd). Among them, compounds (1c) and (1g) presented better selective index (SI) than Bzd. In addition, compounds showed inhibitory activity against the cruzain protease. As observed by electron microscopy, compound (1c) treatment caused irreversible and specific morphological changes on ultrastructure organization of T. cruzi, demonstrating that this class of compounds is killing parasites

Phthalimido-thiazoles as building blocks and their effects on the growth and morphology of Trypanosoma cruzi.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-13T16:12:59Z No. of bitstreams: 1 Gomes PATM Phthalimido....pdf: 1703584 bytes, checksum: 52e53fea525abd4a9ca1d384144f5738 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-05-13T17:31:23Z (GMT) No. of bitstreams: 1 Gomes PATM Phthalimido....pdf: 1703584 bytes, checksum: 52e53fea525abd4a9ca1d384144f5738 (MD5)Made available in DSpace on 2016-05-13T17:31:23Z (GMT). No. of bitstreams: 1 Gomes PATM Phthalimido....pdf: 1703584 bytes, checksum: 52e53fea525abd4a9ca1d384144f5738 (MD5) Previous issue date: 2016Universidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilLaboratório de Imunologia Keizo Asami-LIKA/UFPE. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Centro de Ciências da Saúde. Recife, PE, BrasilChagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 6e7 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases; however, its efficacy during the symptomatic chronic phase is controversial. The present work reports the synthesis and anti-T. cruzi activities of a novel series of phthalimido-thiazoles. Some of these compounds showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in spleen cells, and the resulting structure-activity relationships are discussed. We also showed that phthalimido-thiazoles induced ultrastructural alterations on morphology, flagellum shortening, chromatin condensation, mitochondria swelling, reservosomes alterations and endoplasmic reticulum dilation. Together, these data revealed, for the first time, a novel series of phthalimido-thiazoles-structure-based compounds with potential effects against T. cruzi and lead-like characteristics against Chagas disease