Neonatal mortality risk of vulnerable newborns by fine stratum of gestational age and birthweight for 230 679 live births in nine low- and middle-income countries, 2000-2017.

OBJECTIVE: To describe the mortality risks by fine strata of gestational age and birthweight among 230 679 live births in nine low- and middle-income countries (LMICs) from 2000 to 2017. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Liveborn infants from 15 population-based cohorts. METHODS: Subnational, population-based studies with high-quality birth outcome data were invited to join the Vulnerable Newborn Measurement Collaboration. All studies included birthweight, gestational age measured by ultrasound or last menstrual period, infant sex and neonatal survival. We defined adequate birthweight as 2500-3999 g (reference category), macrosomia as ≥4000 g, moderate low as 1500-2499 g and very low birthweight as <1500 g. We analysed fine strata classifications of preterm, term and post-term: ≥42+0 , 39+0 -41+6 (reference category), 37+0 -38+6 , 34+0 -36+6 ,34+0 -36+6 ,32+0 -33+6 , 30+0 -31+6 , 28+0 -29+6 and less than 28 weeks. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for neonatal mortality rates (NMR) and relative risks (RR). We also performed meta-analysis for the relative mortality risks with 95% confidence intervals (CIs) by the fine categories, stratified by regional study setting (sub-Saharan Africa and Southern Asia) and study-level NMR (≤25 versus >25 neonatal deaths per 1000 live births). RESULTS: We found a dose-response relationship between lower gestational ages and birthweights with increasing neonatal mortality risks. The highest NMR and RR were among preterm babies born at <28 weeks (median NMR 359.2 per 1000 live births; RR 18.0, 95% CI 8.6-37.6) and very low birthweight (462.8 per 1000 live births; RR 43.4, 95% CI 29.5-63.9). We found no statistically significant neonatal mortality risk for macrosomia (RR 1.1, 95% CI 0.6-3.0) but a statistically significant risk for all preterm babies, post-term babies (RR 1.3, 95% CI 1.1-1.5) and babies born at 370 -386 weeks (RR 1.2, 95% CI 1.0-1.4). There were no statistically significant differences by region or underlying neonatal mortality. CONCLUSIONS: In addition to tracking vulnerable newborn types, monitoring finer categories of birthweight and gestational age will allow for better understanding of the predictors, interventions and health outcomes for vulnerable newborns. It is imperative that all newborns from live births and stillbirths have an accurate recorded weight and gestational age to track maternal and neonatal health and optimise prevention and care of vulnerable newborns.

Quality of vital event data for infant mortality estimation in prospective, population-based studies: an analysis of secondary data from Asia, Africa, and Latin America.

INTRODUCTION: Infant and neonatal mortality estimates are typically derived from retrospective birth histories collected through surveys in countries with unreliable civil registration and vital statistics systems. Yet such data are subject to biases, including under-reporting of deaths and age misreporting, which impact mortality estimates. Prospective population-based cohort studies are an underutilized data source for mortality estimation that may offer strengths that avoid biases. METHODS: We conducted a secondary analysis of data from the Child Health Epidemiology Reference Group, including 11 population-based pregnancy or birth cohort studies, to evaluate the appropriateness of vital event data for mortality estimation. Analyses were descriptive, summarizing study designs, populations, protocols, and internal checks to assess their impact on data quality. We calculated infant and neonatal morality rates and compared patterns with Demographic and Health Survey (DHS) data. RESULTS: Studies yielded 71,760 pregnant women and 85,095 live births. Specific field protocols, especially pregnancy enrollment, limited exclusion criteria, and frequent follow-up visits after delivery, led to higher birth outcome ascertainment and fewer missing deaths. Most studies had low follow-up loss in pregnancy and the first month with little evidence of date heaping. Among studies in Asia and Latin America, neonatal mortality rates (NMR) were similar to DHS, while several studies in Sub-Saharan Africa had lower NMRs than DHS. Infant mortality varied by study and region between sources. CONCLUSIONS: Prospective, population-based cohort studies following rigorous protocols can yield high-quality vital event data to improve characterization of detailed mortality patterns of infants in low- and middle-income countries, especially in the early neonatal period where mortality risk is highest and changes rapidly.

Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.

OBJECTIVE: We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). DESIGN: Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. SETTING: Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. POPULATION: Live birth neonates. METHODS: We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. MAIN OUTCOME MEASURES: Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. RESULTS: There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. CONCLUSIONS: Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.

Construction and validation of the Oxford Neurodevelopment Assessment (OX-NDA) in 1-year-old Brazilian children.

BACKGROUND: Over 250 million children under 5 years, globally, are at risk of developmental delay. Interventions during the first 2 years of life have enduring positive effects if children at risk are identified, using standardized assessments, within this window. However, identifying developmental delay during infancy is challenging and there are limited infant development assessments suitable for use in low- and middle-income (LMIC) settings. Here, we describe a new tool, the Oxford Neurodevelopment Assessment (OX-NDA), measuring cognition, language, motor, and behaviour, outcomes in 1-year-old children. We present the results of its evaluation against the Bayley Scales of Infant Development IIIrd edition (BSID-III) and its psychometric properties. METHODS: Sixteen international tools measuring infant development were analysed to inform the OX-NDA's construction. Its agreement with the BSID-III, for cognitive, motor and language domains, was evaluated using intra-class correlations (ICCs, for absolute agreement), Bland-Altman analyses (for bias and limits of agreement), and sensitivity and specificity analyses (for accuracy) in 104 Brazilian children, aged 12 months (SD 8.4 days), recruited from the 2015 Pelotas Birth Cohort Study. Behaviour was not evaluated, as the BSID-III's adaptive behaviour scale was not included in the cohort's protocol. Cohen's kappas and Cronbach's alphas were calculated to determine the OX-NDA's reliability and internal consistency respectively. RESULTS: Agreement was moderate for cognition and motor outcomes (ICCs 0.63 and 0.68, p < 0.001) and low for language outcomes (ICC 0.30, p < 0.04). Bland-Altman analysis showed little to no bias between measures across domains. The OX-NDA's sensitivity and specificity for predicting moderate-to-severe delay on the BSID-III was 76, 73 and 43% and 75, 80 and 33% for cognition, motor and language outcomes, respectively. Inter-rater (k = 0.80-0.96) and test-rest (k = 0.85-0.94) reliability was high for all domains. Administration time was < 20 minutes. CONCLUSION: The OX-NDA shows moderate agreement with the BSID-III for identifying infants at risk of cognitive and motor delay; agreement was low for language delay. It is a rapid, low-cost assessment constructed specifically for use in LMIC populations. Further work is needed to evaluate its use (i) across domains in populations beyond Brazil and (ii) to identify language delays in Brazilian children.

Slow Spread of SARS-CoV-2 in Southern Brazil Over a 6-Month Period: Report on 8 Sequential Statewide Serological Surveys Including 35 611 Participants.

Objectives. To evaluate the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) over 6 months in the Brazilian State of Rio Grande do Sul (population 11.3 million), based on 8 serological surveys. Methods. In each survey, 4151 participants in round 1 and 4460 participants in round 2 were randomly sampled from all state regions. We assessed presence of antibodies against SARS-CoV-2 using a validated lateral flow point-of-care test; we adjusted figures for the time-dependent decay of antibodies. Results. The SARS-CoV-2 antibody prevalence increased from 0.03% (95% confidence interval [CI] = 0.00%, 0.34%; 1 in every 3333 individuals) in mid-April to 1.89% (95% CI = 1.36%, 2.54%; 1 in every 53 individuals) in early September. Prevalence was similar across gender and skin color categories. Older adults were less likely to be infected than younger participants. The proportion of the population who reported leaving home daily increased from 21.4% (95% CI = 20.2%, 22.7%) to 33.2% (95% CI = 31.8%, 34.5%). Conclusions. SARS-CoV-2 infection increased slowly during the first 6 months in the state, differently from what was observed in other Brazilian regions. Future survey rounds will continue to document the spread of the pandemic.

Maternal perinatal depression and infant sleep problems at 1 year of age: Subjective and actigraphy data from a population-based birth cohort study.

This study used data from 2,222 mothers and infants participating in a population-based birth cohort to verify whether maternal depression in the perinatal period was associated with poor infant sleep. Mothers who scored ≥13 points on the Edinburgh Postnatal Depression Scale at 16-24 weeks of gestation and/or 3 months after delivery were considered perinatally depressed. The main outcome variable was poor infant sleep at 12 months of age, defined as >3 night wakings, nocturnal wakefulness >1 hr or total sleep duration <9 hr. Infant sleep data were obtained with the Brief Infant Sleep Questionnaire (BISQ) and 24-hr actigraphy monitoring. Prevalence of perinatal depression in the sample was 22.3% (95% confidence interval [CI], 20.5-24.0). After Poisson regression, infants of depressed mothers showed an adjusted relative risk (RR) of 1.44 (95% CI, 1.00-2.08; p = .04) for >3 night wakings with questionnaire-derived data. When actigraphy data were analysed, no association was found between perinatal depression and poor infant sleep (adjusted RR, 1.20; 95% CI, 0.82-1.74; p = .35). In conclusion, although mothers in the depressed group were more likely to report more night wakings, objective data from actigraphy did not replicate this finding. Dysfunctional cognition, maternal behavioural factors and sleep impairment associated with perinatal depression may affect the mother's impression of her infant's sleep.

Periodontal disease and preterm birth: Findings from the 2015 Pelotas birth cohort study.

OBJECTIVES: To verify the association between periodontal conditions and preterm birth. MATERIALS AND METHODS: This study used data from the 2015 Pelotas Birth Cohort Study, Brazil. Pregnant women expected to give birth in 2015 were interviewed and dentally examined by a trained dentist, with periodontal measures collected in all teeth, six sites per tooth. Exposure was periodontal disease. Outcomes were preterm birth (all births <37 weeks of gestational age) and early preterm birth (<34 weeks). Analysis was carried out using Poisson regression according to a directed acyclic graph. RESULTS: A total of 2,474 women participated in the study. Incidence of preterm births was 10.2% and of early preterm births was 3.5%. Frequency of gingivitis was 21.7%, and periodontitis was 14.9%. Periodontitis was associated with a risk almost two times higher of having early preterm delivery compared with healthy pregnant women (RR 1.93; 95% CI 1.09-3.43). Presence of 5+ mm periodontal pocket with bleeding on probing was also associated with higher risk for early preterm delivery. CONCLUSIONS: The association between periodontal disease in pregnancy and the occurrence of preterm delivery is sensitive to the case definitions. Periodontal disease increased the risk of early preterm delivery.

[Prevalence of antibodies against SARS-CoV-2 according to socioeconomic and ethnic status in a nationwide Brazilian surveyPrevalência de anticorpos contra o SARS-CoV-2 de acordo com o status socioeconômico e étnico em uma pesquisa nacional no Brasil]. / Prevalencia de anticuerpos contra el SARS-CoV-2 según el estatus socioeconómico y étnico en una encuesta nacional de Brasil.

OBJECTIVES: To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil. METHODS: In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses. RESULTS: 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant. CONCLUSIONS: The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

OBJETIVOS: Investigar as desigualdades socioeconômicas e étnicas na prevalência de anticorpos contra SARS-CoV-2 nas 27 unidades federativas do Brasil. MÉTODOS: Neste estudo transversal, três pesquisas domiciliares foram realizadas de 14 a 21 de maio, 4 a 7 de junho, e 21-24 de junho, 2020 em 133 áreas urbanas brasileiras. Amostragem em várias etapas foi utilizada para selecionar 250 indivíduos em cada cidade para se submeter a um teste rápido de anticorpos. Os sujeitos responderam a um questionário sobre bens domésticos, escolaridade e cor da pele/etnicidade (auto-relatada utilizando a classificação padrão brasileira de cinco categorias: branco, preto, pardo, asiático ou indígena). A análise dos componentes principais dos ativos foi utilizada para classificar a posição socioeconómica em cinco quintis de riqueza. A regressão de Poisson foi utilizada para as análises. RESULTADOS: 25 025 indivíduos foram testados na primeira pesquisa, 31 165 na segunda, e 33 207 na terceira, com prevalência de resultados positivos de 1,4%, 2,4% e 2,9%, respectivamente. Indivíduos no quintil mais pobre tinham 2,16 vezes (intervalo de confiança de 95% 1,86; 2,51) mais probabilidade de ter um resultado positivo do que aqueles do quintil mais rico, e aqueles com 12 ou mais anos de escolaridade tinham uma prevalência menor do que aqueles com menos educação. Os indivíduos indígenas tinham 4,71 (3,65; 6,08) vezes mais prevalência do que os brancos, assim como aqueles com cor da pele preta ou parda. O ajuste regional reduziu as taxas de prevalência de acordo com a riqueza, educação e etnia, mas os resultados permaneceram estatisticamente significativos. CONCLUSÕES: A prevalência de anticorpos contra a SARS-CoV-2 no Brasil mostra gradientes relacionados com a posição socioeconómica e a etnia muito acentuados, com os menores riscos entre os indivíduos brancos, educados e ricos.

Prevalence of antibodies against SARS-CoV-2 according to socioeconomic and ethnic status in a nationwide Brazilian survey.

OBJECTIVES: To investigate socioeconomic and ethnic group inequalities in prevalence of antibodies against SARS-CoV-2 in the 27 federative units of Brazil. METHODS: In this cross-sectional study, three household surveys were carried out on May 14-21, June 4-7, and June 21-24, 2020 in 133 Brazilian urban areas. Multi-stage sampling was used to select 250 individuals in each city to undergo a rapid antibody test. Subjects answered a questionnaire on household assets, schooling and self-reported skin color/ethnicity using the standard Brazilian classification in five categories: white, black, brown, Asian or indigenous. Principal component analyses of assets was used to classify socioeconomic position into five wealth quintiles. Poisson regression was used for the analyses. RESULTS: 25 025 subjects were tested in the first, 31 165 in the second, and 33 207 in the third wave of the survey, with prevalence of positive results equal to 1.4%, 2.4%, and 2.9% respectively. Individuals in the poorest quintile were 2.16 times (95% confidence interval 1.86; 2.51) more likely to test positive than those in the wealthiest quintile, and those with 12 or more years of schooling had lower prevalence than subjects with less education. Indigenous individuals had 4.71 (3.65; 6.08) times higher prevalence than whites, as did those with black or brown skin color. Adjustment for region of the country reduced the prevalence ratios according to wealth, education and ethnicity, but results remained statistically significant. CONCLUSIONS: The prevalence of antibodies against SARS-CoV-2 in Brazil shows steep class and ethnic gradients, with lowest risks among white, educated and wealthy individuals.

Cordycepin (3'-deoxyadenosine) and pentostatin (deoxycoformycin) against Trypanosoma cruzi.

The aim of this study was to evaluate in vitro the efficacy of cordycepin and pentostatin (alone or combined) against Trypanosoma cruzi, as well as the therapeutic efficiency of protocols of cordycepin and pentostatin combinations in mice experimentally infected with T. cruzi. In vitro, the cordycepin (3'-deoxyadenosine) and pentostatin (deoxycoformycin) exerted potent trypanocidal effect against T. cruzi (Colombian strain), similarly to benznidazole, which is the reference drug. For epimastigotes, the lethal dose of cordycepin capable of killing 50% (LD50) and 20% (LD20) of the parasites was 0.072 and 0.031 mg/mL, respectively and for trypomastigotes was 0.047 and 0.015 mg/mL, respectively. The combined use of cordycepin and pentostatin resulted in a LD50 and LD20 for epimastigotes of 0.068 and 0.027 mg/mL, respectively, as well as 0.056 and 0.018 mg/mL for trypomastigotes, respectively. In vivo, the combined use of cordycepin and pentostatin did not show the expected curative effect, however it was able to control the parasitema in the peak period. In summary, the combination of cordycepin and pentostatin showed no curative effect in mice infected by T. cruzi, despite the in vitro reduction of epimastigotes and trypomastigotes.

Evolution towards the elimination of congenital syphilis in Latin America and the Caribbean: a multicountry analysis.

OBJECTIVE: Effective and low-cost interventions for preventing the vertical transmission of syphilis can substantially reduce mortality and morbidity related to maternal and congenital syphilis. This study aims to identify successes and problems in eliminating congenital syphilis in Latin America and the Caribbean (LAC). METHODS: Conducted in 2015, this multicountry study included qualitative data from focal point staff members of the Pan American Health Organization, as well as country information and answers to semiqualitative questions on the elimination of congenital syphilis. Additional information was obtained from five Caribbean countries and Panama. RESULTS: Few of the studied LAC countries use a rapid syphilis test, but most of them do have benzathine penicillin available in primary care facilities. The majority of the countries have national strategies and protocols for eliminating congenital syphilis. There were substantial differences among the national information systems, including with data collection, analysis, and quality control. The major challenges related to eliminating congenital syphilis are the need to improve: prenatal care; test coverage; health worker training about syphilis diagnosis, treatment, and follow-up; and access to institutional deliveries. Other problems include a lack of rapid tests; shortages of benzathine penicillin; and substandard laboratory quality. Poor follow-up of maternal syphilis cases and their sexual contacts was also reported. CONCLUSIONS: Most of the LAC countries studied have national strategic plans and protocols and have advanced in the elimination of congenital syphilis. These countries must keep improving their capacity to collect high-quality data about coverage and inequities and use this data as a basis for decision-making. To accelerate the elimination of congenital syphilis, the good practices and actions that have been undertaken must be reinforced.

Nucleotide and nucleoside involvement in immunomodulation in experimental Chagas disease.

The aim of this study was to evaluate whether Trypanosma cruzi infections cause alterations in the levels of seric purines, which could contribute to host immunomodulation. Twelve mice were divided into two groups identified as control (uninfected) and infected (T. cruzi) groups. The influence of the disease on seric purine levels was verified on day 20 post-infection (PI) by HPLC. Infected mice had circulating trypomastigotes during the experiment, as well as amastigote forms in the heart associated with inflammatory infiltrates. Increases on adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine (ADO), inosine (INO), and uric acid (URIC) levels were observed in the infected animals, while the adenosine monophosphate (AMP) and xanthine (XAN) levels were reduced compared with mice of the control group, indicating a possible impairment on the purinergic system, and consequently, on the immune system during the clinical course of the disease. In summary, the T. cruzi infection alters the seric purine levels, and consequently, modulates the immune system.

Removal of synthetic sex hormones by hydrothermal carbonization.

One of the most prominent fields of environmental chemistry is the study and the removal of micro-pollutants from aqueous matrices. Analytical techniques for their identification and quantification are becoming more sensitive and comprehensive and, as a result, an increasing number of drugs have been detected in environmental samples. However, the literature shows that conventional treatments for drinking water and wastewater are not sufficient for remove these compounds. This study aims to check whether the process of hydrothermal carbonization (CHT) is effective in removing the synthetic sex hormones: ethinyl estradiol, gestodene and cyproterone acetate from aqueous samples. The system used in CHT basically consists of a pressurized reactor made of stainless steel and solutions of compounds of interest, both individual and mixed, with a concentration of 1.0 µg.L-1 and a pH range of 2.0 to 3.0. The maximum surface temperature in the reactor was about 180 °C, the internal pressure was 20 bar with 90 minutes for the reaction. Four experiments were conducted, one for each hormone and one with the three hormones together. In individual tests removal of the compounds was found to be 99.8% for ethinyl estradiol, 99.3% for gestodene and 100% for cyproterone acetate. For a mixture of the hormones treated under the same conditions, the mean values of CHT-removal of Ethinylestradiol, Gestodene and Cyproterone Acetate were 99.60%, 96.80% and 68.90%, respectively. The impact of the matrix effect may have affected the efficiency of the hormone removal process by CHT.

The associations that income, education, and ethnicity have with birthweight and prematurity: how close are they?

OBJECTIVES: To identify evidence that income, education, or ethnicity might be associated with low birthweight, small-for-gestational-age birth, or preterm birth. METHODS: A systematic review was conducted using searches in two online databases, PubMed and Literature in the Health Sciences in Latin America and the Caribbean (LILACS). The searches covered materials published between 1 January 1982 and 5 May 2016. The search terms used were ("infant, premature" OR "infant, small for gestational age" OR "fetal growth retardation") AND ("socioeconomic factors" OR "ethnic groups" OR "maternal age"). RESULTS: A total of 3 070 references that met the initial selection criteria were analyzed, and 157 relevant studies were fully read. We located 18 studies that investigated associations of family or maternal income, education, or ethnicity with low birthweight, small-for-gestational-age birth, or preterm birth. Of the 18, 10 of them involved high-income countries, and 8 dealt with middle- or low-income countries. Greater evidence was found for an association between ethnicity and the three outcomes studied, particularly for prematurity among children of black mothers. There was little evidence for an association between maternal/family income or education and any of the three outcomes. CONCLUSIONS: Income and education weren't determinants for low birthweight, small-for-gestational-age birth, or preterm birth. However, black ethnicity was strongly associated with the three outcomes, especially with prematurity.

Cupuaçu (Theobroma grandiflorum) residue and its potential application in the bioremediation of 17-Α-ethinylestradiol as a Pycnoporus sanguineus laccase inducer.

Bioremediation is a strategy to mitigate environmental impacts of hazardous pollutants from anthropogenic sources. Natural byproducts, including agroindustrial wastes (AW) can be used to induce enzyme biosynthesis, leading up to enhancement of pollutants degradation process. Therefore, this study aimed to evaluate the use of cupuaçu, Theobroma grandiflorum AW as Pycnoporus sanguineus Laccase (Lac) inducer in order to promote 17-α-ethinylestradiol (EE2) bioremediation. The macro and micro-nutrients levels of cupuaçu AWs were evaluated in order to establish further correlations with enzymatic biosynthesis induction. The fungus was cultivated for 7 days in temperature of 28 ± 2 °C and agitation of 150 rpm. For bioremediation, Lac enzymatic extract was added to EE2 solution (10 µg mL-1) and the percentage of removal was evaluated by HPLC after 1-24 hr of reaction. At optimized conditions, the enzyme extract production was remarkably enhanced by adding only 1% (w/v) of cupuaçu AW. Lac activity reached 1642 U mL-1 on the 6th day of culture, which was higher than positive control (511 U mL-1). 86% of EE2 removal was reached after 4 hr, and after 8 hr of reaction, 96.5% was removed. Analysis by direct infusion in MS-ESI-TOF exhibited intermediary compounds formed by radical hydroxilation.

Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation.

BACKGROUND: In November, 2015, an epidemic of microcephaly was reported in Brazil, which was later attributed to congenital Zika virus infection. 7830 suspected cases had been reported to the Brazilian Ministry of Health by June 4, 2016, but little is known about their characteristics. We aimed to describe these newborn babies in terms of clinical findings, anthropometry, and survival. METHODS: We reviewed all 1501 liveborn infants for whom investigation by medical teams at State level had been completed as of Feb 27, 2016, and classified suspected cases into five categories based on neuroimaging and laboratory results for Zika virus and other relevant infections. Definite cases had laboratory evidence of Zika virus infection; highly probable cases presented specific neuroimaging findings, and negative laboratory results for other congenital infections; moderately probable cases had specific imaging findings but other infections could not be ruled out; somewhat probable cases had imaging findings, but these were not reported in detail by the local teams; all other newborn babies were classified as discarded cases. Head circumference by gestational age was assessed with InterGrowth standards. First week mortality and history of rash were provided by the State medical teams. FINDINGS: Between Nov 19, 2015, and Feb 27, 2015, investigations were completed for 1501 suspected cases reported to the Brazilian Ministry of Health, of whom 899 were discarded. Of the remainder 602 cases, 76 were definite, 54 highly probable, 181 moderately probable, and 291 somewhat probable of congenital Zika virus syndrome. Clinical, anthropometric, and survival differences were small among the four groups. Compared with these four groups, the 899 discarded cases had larger head circumferences (mean Z scores -1·54 vs -3·13, difference 1·58 [95% CI 1·45-1·72]); lower first-week mortality (14 per 1000 vs 51 per 1000; rate ratio 0·28 [95% CI 0·14-0·56]); and were less likely to have a history of rash during pregnancy (20·7% vs 61·4%, ratio 0·34 [95% CI 0·27-0·42]). Rashes in the third trimester of pregnancy were associated with brain abnormalities despite normal sized heads. One in five definite or probable cases presented head circumferences in the normal range (above -2 SD below the median of the InterGrowth standard) and for one third of definite and probable cases there was no history of a rash during pregnancy. The peak of the epidemic occurred in late November, 2015. INTERPRETATION: Zika virus congenital syndrome is a new teratogenic disease. Because many definite or probable cases present normal head circumference values and their mothers do not report having a rash, screening criteria must be revised in order to detect all affected newborn babies. FUNDING: Brazilian Ministry of Health, Pan American Health Organization, and Wellcome Trust.

High-risk papillomavirus infection among women living with human Immunodeficiency virus: Brazilian multicentric study.

Cervical cancer is an important health issue in Latin America. Although HPV infections can have spontaneous clearance, persistence of high-risk (HR) HPV is a risk factor for cervical cancer among women and it is even higher in HIV-infected women. To determine the prevalence of HR-HPV and risk factors among HIV-infected women attending reference services for HIV/AIDS in different regions of Brazil. Cross-sectional study conducted among HIV-infected women attended at referral care centers for HIV/AIDS in nine states of Brazil. Women from 18 to 49 years that accept to participate and were not pregnant at the time of the approach were recruited for the study. The HPV screening was realized using qPCR in closed system, in vitro Diagnostic, COBAS® -HPV Roche. The cytology results were available by the Bethesda System. A total of 802(89.1%) from the selected women agreed to participate in the study. Median age was 39(Inter quartile range [IQR34-46]) years and median education was 9(IQR6-11) years. General prevalence of HR-HPV was 28.4%(228/802). HPV-16 prevalence rate was 8.1%(65/802), HPV-18 was 3.7%(30/802) and other types of HR-HPV were 23.6% (189/802). Risk factors for HR-HPV infection in the multivariate logistic regression analysis were: age ranging from 18 to 34 years (OR = 1.43[95%CI:1.18-1.75]), illicit drugs use (OR = 1.61[95%CI:1.10-2.42]) and abnormal cervical cytology (OR = 1.56[95%CI:1.34-1.81]). Results showed a prevalence rate of 28.4% of HR-HPV infection in women living with HIV in Brazil. These infections were significantly associated with having less than 35 years old, illicit drug use and abnormal cervical cytology.

Treatment with 3'-deoxyadenosine and deoxycoformycin in mice infected by Trypanosoma cruzi and its side effect on purinergic enzymes.

The aim of this study was to evaluate the efficacy of 3'-deoxyadenosine and deoxycoformycin combination in the treatment of mice infected by T. cruzi, as well as to verify the influence of the treatment on purinergic enzymes. Heart and serum samples were collected from 60 mice (30 infected and 30 uninfected) at day 12 post-infection. To verify treatment efficacy, parasitemia was monitored, and the treatment with 3'-deoxy adenosine and deoxycoformycin combination was able to reduce it, but had no curative effect on mice. Seric activities of NTPDase (ATP and ADP substrate) and ADA were increased significantly in untreated mice infected by T. cruzi compared to the negative control, as well as mice treated with 3'-deoxyadenosine and deoxycoformycin (alone or combined) modulated the activity of NTPDase (ATP and ADP substrate), preventing them from increasing in infected animals (activity similar to healthy animals). Treatment with deoxycoformycin alone and associated with 3'-deoxyadenosine modulated the activity of ADA preventing them from increasing in infected animals. However, seric activities of ADA in mice treated with 3'-deoxyadenosine (cordycepin) alone does not modify the ADA activity compared with infected and non-treated mice. However, the 5'-nucleotidase activity decreased significantly in infected untreated animals and the same occurred in infected and treated animals with deoxycoformycin and 3'-deoxyadenosine. However, treatment with deoxycoformycin associated with 3'-deoxyadenosine preventing them from decreasing the 5'-nucleotidase activity. Therefore, we conclude that the treatments did not have curative success for mice infected by T. cruzi. However, the treatments were able to modulate the purinergic enzymes during the infection by T. cruzi, which may contribute to reduce the inflammatory damage in heart.

Purinergic ecto-enzymes participate in the thromboregulation in acute in mice infection by Trypanosoma cruzi.

Coagulation disorders have been described in Chagas disease with thrombocytopenia as an important event. Several mechanisms may be related to this pathogenesis, such as enzymes of the purinergic system, purine, and receptors involved in the regulation and modulation of physiological events related to hemostasis. Therefore, the aim of this study was to evaluate the activities of E-NTPDase, E-5'nucleotidase, and ecto-adenosine deaminase (E-ADA) in platelets of mice experimentally infected by Trypanosoma cruzi. Twelve female mice were used, divided into two groups (n = 6): uninfected and infected. Mice of infected group were intraperitoneally inoculated with 104 trypomastigotes of T. cruzi (strain Y). On day 12 post-infection (PI), blood samples were collected for quantitation and separation of platelets. A significant reduction in the number of platelets of infected mice (P < 0.05) was observed. The activities of E-NTPDase (ATP and ADP substrates), E-5'nucleotidase, and E-ADA in platelets increased significantly (P < 0.05) in mice infected by T. cruzi compared with uninfected animals. A negative correlation (P < 0.01)was observed between the number of platelets and ATP hydrolysis (r = -0.64), and ADP hydrolysis (r = -0.69) by E-NTPDase. Therefore, there is a response from the purinergic system activating ecto-enzymes in platelets of mice T. cruzi infected, as a compensatory effect of thrombocytopenia.

Solving the challenge of the blood-brain barrier to treat infections caused by Trypanosoma evansi: evaluation of nerolidol-loaded nanospheres in mice.

Despite significant advances in therapies against Trypanosoma evansi, its effective elimination from the central nervous system (CNS) remains a difficult task. The incapacity of trypanocidal drugs to cross the blood-brain barrier (BBB) after systemic administrations makes the brain the main refuge area for T. evansi. Nanotechnology is showing great potential to improve drug efficacy, such as nerolidol-loaded nanospheres (N-NS). Thus, the aim of this study was to investigate whether the treatment with N-NS was able to cross the BBB and to eliminate T. evansi from the CNS. High-performance liquid chromatography revealed that N-NS can cross the BBB of T. evansi-infected mice, while free nerolidol (F-N) neither the trypanocidal drug diminazene aceturate (D.A.) were not detected in the brain tissue. Polymerase chain reaction revealed that 100% of the animals treated with N-NS were negatives for T. evansi in the brain tissue, while all infected animals treated with F-N or D.A. were positives. Thus, we concluded that nanotechnology improves the therapeutic efficacy of nerolidol, and enables the transport of its active principle through the BBB. In summary, N-NS treatment can eliminate the parasite from the CNS, and possesses potential to treat infected animals.