The translational challenge in chagas disease drug development

Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.Fil: Kratz, Jadel M.. No especifíca;Fil: Gonçalves, Karolina R.. Universidade de Sao Paulo; BrasilFil: Romera, Lavínia M. D.. Universidade de Sao Paulo; BrasilFil: Borsoi Moraes, Carolina. Universidade Federal de Sao Paulo; BrasilFil: Bittencourt Cunha, Paula. Universidade de Sao Paulo; Brasil. Universidade Federal de Sao Paulo; BrasilFil: Schenkman, Sergio. Universidade Federal de Sao Paulo; BrasilFil: Chatelain, Eric. No especifíca;Fil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentin

Growth, nutrition and biological fixation of nitrogen in mixed-species plantations of eucalypt with leguminous trees

O objetivo deste trabalho foi avaliar o crescimento inicial da parte aérea e do sistema radicular, a nutrição mineral e a fixação biológica de N2 (FBN) em plantios consorciados de Eucalyptus grandis e leguminosas arbóreas. O delineamento experimental foi o de blocos ao acaso com três repetições e sete tratamentos por bloco. Nas linhas de plantio, entre as plantas de E. grandis, foram plantadas, intercaladamente, leguminosas arbóreas nativas de matas brasileiras – Peltophorum dubium, Inga sp., Mimosa scabrella, Acacia polyphylla, Mimosa caesalpiniaefolia – e uma leguminosa exótica, Acacia mangium. Realizou-se, também, o plantio puro de E. grandis. Mimosa scabrella e A. mangium foram as leguminosas com maior crescimento. Eucalyptus grandis consorciado com M. scabrella cresceu menos, no entanto foi o povoamento com maior acumulação de biomassa. As densidades de raízes finas (DRF) do E. grandis foram 6 a 20 vezes maiores que as DRF das leguminosas na camada superficial do solo (0–10 cm) 24 meses após plantio. A DRF de M. scabrella e de M. caesalpiniaefolia foi maior na camada 30–50 cm e menor na camada 10–30 cm. Os valores de d15N da M. scabrella indicam que 90% do N acumulado em seus tecidos é oriundo da FBN.The objective of this work was to assess interactions between species on the above and belowground growth, nitrogen uptake and biological nitrogen fixation (BNF) in mixed stands of Eucalyptus grandis and native leguminous N2-fixing trees. A complete randomized block design was installed with seven treatments and three blocks. Within the lines of the E. grandis seedlings, native leguminous N2-fixing trees – Peltophorum dubium, Inga sp., Mimosa scabrella, Acacia polyphylla, Mimosa caesalpiniaefolia – and one exotic leguminous plant, Acacia mangium, were intercropped. E. grandis was also solely planted. Mimosa scabrella and A. mangium were the legume trees that presented the highest growth. Although E. grandis showed a lower growth when combined with M. scabrella, this mixed-species stand exhibited the highest biomass accumulation. Eucalyptus grandis fine root densities (FRD) were 6–20 times higher than the FRD of the leguminous species in the upper soil layer (0–10 cm) 24 months after planting. The FRD of M. scabrella and M. caesalpiniaefolia in the 30–50 cm soil layer was higher than in the 10–30 cm layer. The d15N values of M. scabrella indicated that 90% of stocked N is derived from BNF

Compostos pseudopeptídicos inibidores da serino protease, composições inibidoras da serino protease e composições farmacêuticas contendo tais compostos

DepositadaRelata compostos pseudopeptídeos inibidores da serino protease que apresentam um cerne rígido derivado do D-manitol, isomanídeo, capaz de conferir rigidez ao inibidor, e que por sua natureza química também pode atuar em polimerases, como DNA ou RNA polimerases, inibindo-as. Esses compostos inibidores de serino proteases e polimerases são base de composições inibidoras da serino protease, bem como composições farmacêuticas destinadas à elaboração de potenciais medicamentos antivirais, contra vírus da família Flaviviridae sendo relacionada, principalmente, aos vírus da Hepatite C (HCV) e o vírus da Dengue

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

Cutting Ability of Nickel-titanium rotary systems protaper, mtwo and k3

Nickel-titanium rotatory systems should remove dentin during the root canal preparation to promote the enlargement and tapered shape with continuously narrowing towards the apex. Objective: The aim of this study was to analyze the cutting ability of three NiTi rotatory systems (n = 12): ProTaper (group 1), Mtwo (group 2), and K3 (group 3). Material and methods: Thirty six maxillary molar teeth were weighted on an analytical balance before and after the rotatory preparation of the mesio-buccal root canal. Data was statistically analyzed by ANOVA and Tukey s test with a significance level of 5%. Results: The results revealed the following mass differences (g) before and after the root canal preparation: ProTaper (group 1 – 0.0159 ± 0.004), Mtwo (group 2 – 0.0125 ± 0.002), and K3 (group 3 – 0.007 ± 0.003). Conclusion: ProTaper showed the highest cutting ability among the three tested nickel-titanium rotatory systems followed by Mtwo and K3

A inovaçâo e os fatores organizacionais característicos

O objetivo do presente estudo é o de identificar os fatores organizacionais determinantes para que uma empresa possa ser considerada inovadora na indústria de equipamentos Eletro-Médicos. A pesquisa foi feita dentro do enfoque quantitativo, intencionando obter a visão dos próprios fabricantes de equipamentos quanto aos fatores organizacionais característicos que contribuem para o sucesso do processo de inovação. Foram pesquisados 46 fabricantes de equipamentos Eletro-Médicos por meio de uma amostra não probabilística por conveniência. A análise quantitativa com tratamento estatístico multivariado, por meio da análise fatorial, indicou a presença de seis fatores respondendo por 80,6% da variância total, sendo que apenas dois fatores determinantes das organizações pesquisadas, �Liderança e Comprometimento� e �Reconhecimento e Interação� respondem respectivamente por 47% e por 9 % da variância total