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ABSTRACT Background: Climate change has significant implications on ecosystems. We verified the effects of climate change on the malaria vector Anopheles aquasalis using simulated climate change scenarios (SSCCs). Methods: An experimental model was designed for SSCCs, which composed of air-conditioned 25 m3 rooms. Results: The wing size was significantly different between SSCCs. A colony of Anopheles aquasalis could not be established in extreme scenarios. Conclusions: Increases in temperature and CO2 in the atmosphere may modify the global epidemiology of malaria, marking its emergence in currently malaria-free areas.

Abstract Background The MTHFR 677C>T variant’s involvement with hyperhomocysteinemia and peripheral arterial disease (PAD) is still unclear. Objectives To evaluate associations between the MTHFR 677C>T (rs1801133) variant and susceptibility to and severity of PAD and homocysteine (Hcy) levels. Methods The study enrolled 157 PAD patients and 113 unrelated controls. PAD severity and anatomoradiological categories were assessed using the Fontaine classification and the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC), respectively. The variant was genotyped using real-time polymerase chain reaction and Hcy levels were determined using chemiluminescence microparticle assay. Results The sample of PAD patients comprised 60 (38.2%) females and 97 (61.8%) males. Patients were older and had higher Hcy than controls (median age of 69 vs. 45 years, pT variant did not differ according to Fontaine or TASC categories. However, Hcy was higher in patients with the CT+TT genotypes than in those with the CC genotype (14.60 µmol/L vs. 12.94 µmol/L, p=0.008). Moreover, patients with the TT genotype had higher Hcy than those with the CC+CT genotypes (16.40 µmol/L vs. 13.22 µmol/L, p=0.019), independently of the major confounding variables. Conclusions The T allele of MTHFR 677C>T variant was associated with higher Hcy levels in PAD patients, but not in controls, suggesting a possible interaction between the MTHFR 677C>T variant and other genetic, epigenetic, or environmental factors associated with PAD, affecting modulation of Hcy metabolism.

Introdução a um programa de pesquisa visando esclarecer uma possível influência dos inseticidas organoclorados na etiologia dos tumores hepáticos primários na população do norte do Estado do Paraná, Brasil.

Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease prevalent in Latin America. Infected patients are treated to eliminate the parasite, reduce the cardiomyopathy risk, and interrupt the disease transmission cycle. The World Health Organization recognizes benznidazole (BZ) and nifurtimox as effective drugs for CD treatment. In the chronic phase, both drugs have low cure rates and serious side effects. T. cruzi infection causes intense tissue inflammation that controls parasite proliferation and CD evolution. Compounds that liberate nitric oxide (NO) (NO donors) have been used as anti-T. cruzi therapeutics. Currently, there is no evidence that nitroxyl (HNO) affects T. cruzi infection outcomes. This study investigated the effects of the HNO donor Angeli’s salt (AS) on C57BL/6 mice infected with T. cruzi (Y strain, 5 × 103 trypomastigotes, intraperitoneally). AS reduced the number of parasites in the bloodstream and heart nests and increased the protective antioxidant capacity of erythrocytes in infected animals, reducing disease severity. Furthermore, in vitro experiments showed that AS treatment reduced parasite uptake and trypomastigote release by macrophages. Taken together, these findings from the murine model and in vitro testing suggest that AS could be a promising therapy for CD.

The Santos and São Vicente Estuarine System (SSVES) is a region with significant economic importance in southeastern Brazil. It contains petrochemical and metallurgical industrial complexes and the largest commercial harbor in South America, which have made the area vulnerable to degradation by chemical pollutants, such as mercury (Hg). This study is the first to evaluate the environmental parameters that control the spatial distribution of Hg in the surface sediments of the SSVES which is influenced mainly by hydrodynamics and total organic carbon. The innermost part of the estuarine system, where weaker currents lead to an environment with more sediment deposition, has anomalous Hg concentrations, reaching values over 7.0 mg kg–1 and enrichment factors of 115, resulting from historical anthropogenic activities. Although there is a low probability of harmful effects of Hg in organisms, this element demonstrates greater mobility and bioavailability in the environment, indicating the need for monitoring Hg for the conservation of this region.

PurposeAlthough the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice.MethodsMale Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting.ResultsResistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia.ConclusionOur results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.

Background Chagas disease is a neglected tropical disease that is still considered a global health emergency. In the Amazon region, most of the reports are of acute cases that are associated with oral transmission. This study aimed to evaluate myocardial injury in patients with acute Chagas disease before and after treatment. Methods and Results We evaluated 23 patients with acute Chagas disease in 3 different stages of progression. Group 1 had 12 patients evaluated during the acute phase, at the time of diagnosis, and 1 year after treatment, and Group 2 had 11 patients in the late postacute phase who were evaluated 5.2 years on average after diagnosis and treatment. ECGs with the Selvester score, 24‐hour Holter exam, and cardiovascular magnetic resonance imaging were performed. The mean age of the 23 patients was 44.3±18.9 years, and they were mostly men (15/65.24%) from Amazonas state (22/95.6%). In 69.6% (n=16) of the patients, some ECG alterations were found, the most frequent being left anterior fascicular block and ventricular repolarization. In Group 1, the 24‐hour Holter exam showed atrial tachycardia in 3 (25%) patients and ventricular extrasystoles in 2 (16.7%) patients. In Group 2, 1 patient had ventricular extrasystoles. Myocardial injury was observed in 7 patients (58.3%) at the acute phase and in 5 (50%) patients at the 1‐year follow‐up in Group 1 and in 2 (18.2%) patients in Group 2. Conclusions This article describes, for the first time, myocardial injury shown by cardiovascular magnetic resonance imaging in a group of patients with acute Chagas disease and reveals the importance of early detection and follow‐up of the cardiac impairment in these patients.

Abstract Background In the Brazilian Amazon, a new epidemiological profile of Chagas disease transmission, the oral route, has been detected and cited as being responsible for the increase in acute cases in Brazil. The clinical evaluation of acute Chagas disease (ACD) has been a challenge since it can progress to a chronic phase with cardiac alterations, and the follow-up by modern diagnostic methods is very difficult due to the socio-geographical characteristics of the Brazilian Amazon. Thus, alternatives should be sought to alleviate this problem. We conducted a study to evaluate subjects with ACD using the 12-lead ECG QRS score (Selvester score) as an estimative of myocardial injury progression before and after ACD treatment. Methods The study included indigenous subjects from the Amazon region with ACD in clinical follow-up at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado (FMT-HVD) Chagas Disease outpatient clinic in the state of Amazonas, Brazil. The control group consisted of 31 healthy volunteers with no history of heart disease and no reactive serology for Chagas disease. Baseline ECG was performed in all subjects. The Selvester scoring method was performed according to the standardized guide ( 3: points × 3% = % of the predicted LV infarction). Results A total of 62 subjects were included, 31 as cases and 31 as controls. The mean follow-up of the case group was 17 months. The control group presented normal ECG. The case group presented 13 alterations before treatment and 11 after. Nineteen individuals presented scores > 3 points, 6 before and 13 after. In 19.36% of subjects, myocardial injury was found before treatment and in 41.94% after treatment. Conclusion This is the first study that uses the Selvester score (SS) to predict myocardial injury in subjects with ACD. The results of this study suggest the significant presence of myocardial injury from the beginning of treatment to the period post treatment of ACD, which demonstrates that the SS can be applied for stratification and follow-up of Chagas disease in the Amazon region.

Medical gas plasmas are of emerging interest in pre-clinical oncological research. Similar to an array of first-line chemotherapeutics and physics-based therapies already approved for clinical application, plasmas target the tumor redox state by generating a variety of highly reactive species eligible for local tumor treatments. Considering internal tumors with limited accessibility, medical gas plasmas help to enrich liquids with stable, low-dose oxidants ideal for intratumoral injection and lavage. Pre-clinical investigation of such liquids in numerous tumor entities and models in vitro and in vivo provided evidence of their clinical relevance, broadening the range of patients that could benefit from medical gas plasma therapy in the future. Likewise, the application of such liquids might be promising for recurrent BRAF(V600E) papillary thyroid carcinomas, resistant to adjuvant administration of radioiodine. From a redox biology point of view, studying redox-based approaches in thyroid carcinomas is particularly interesting, as they evolve in a highly oxidative environment requiring the capability to cope with large amounts of ROS/RNS. Knowledge on their behavior under different redox conditions is scarce. The present study aimed to clarify resistance, proliferative activity, and the oxidative stress response of human papillary thyroid cancer cells K1 after exposure to plasma-oxidized DMEM (oxDMEM). Cellular responses were also evaluated when treated with different dosages of hydrogen peroxide and the RNS donor sodium nitroprusside (SNP). Our findings outline plasma-oxidized liquids as a promising approach targeting BRAF(V600E) papillary thyroid carcinomas and extend current knowledge on the susceptibility of cells to undergo ROS/RNS-induced cell death.

Abstract Background Elimination of malaria depends on mastering transmission and understanding the biological basis of Plasmodium infection in the vector. The first mosquito organ to interact with the parasite is the midgut and its transcriptomic characterization during infection can reveal effective antiplasmodial responses able to limit the survival of the parasite. The vector response to Plasmodium vivax is not fully characterized, and its specificities when compared with other malaria parasites can be of fundamental interest for specific control measures. Methods Experimental infections were performed using a membrane-feeding device. Three groups were used: P. vivax-blood-fed, blood-fed on inactivated gametocytes, and unfed mosquitoes. Twenty-four hours after feeding, the mosquitoes were dissected and the midgut collected for transcriptomic analysis using RNAseq. Nine cDNA libraries were generated and sequenced on an Illumina HiSeq2500. Readings were checked for quality control and analysed using the Trinity platform for de novo transcriptome assembly. Transcript quantification was performed and the transcriptome was functionally annotated. Differential expression gene analysis was carried out. The role of the identified mechanisms was further explored using functional approaches. Results Forty-nine genes were identified as being differentially expressed with P. vivax infection: 34 were upregulated and 15 were downregulated. Half of the P. vivax-related differentially expressed genes could be related to autophagy; therefore, the effect of the known inhibitor (wortmannin) and activator (spermidine) was tested on the infection outcome. Autophagic activation significantly reduced the intensity and prevalence of infection. This was associated with transcription alterations of the autophagy regulating genes Beclin, DRAM and Apg8. Conclusions Our data indicate that P. vivax invasion of An. aquasalis midgut epithelium triggers an autophagic response and its activation reduces infection. This suggests a novel mechanism that mosquitoes can use to fight Plasmodium infection.

Abstract Chagas disease is caused by the protozoan Trypanosoma cruzi. Seven lineages have been identified based on different molecular markers, namely TcI, TcII, TcIII, TcIV, TcV, TcVI, and TcBat. Dogs play the role of epidemiological sentinels being domestic reservoirs of T. cruzi. The aim of the current study was to report the first case of CD in a domestic dog in Manaus, Amazonas, Brazil, infected with T. cruzi DTU TcIV. We hope our report encourages veterinarians and surveillance professionals to a take a deeper look at T. cruzi infection in domestic animals.

The analysis of hydrocarbons in terms of individual compounds is relevant to understand the origin and source of these substances, as well as its distribution in environmental compartments, including sediments and biota. Hydrocarbons concentrations were determined in sediments and in whole-body soft tissues of the tropical clam Anomalocardia flexuosa in sediment toxicity testing using samples of Mucuripe bay (Ceará State, NE Brazil) collected in 2011 during dredging events [1]. Data of target compounds included aliphatic (AHs) and aromatic hydrocarbons (PAHs), and linear alkylbenzenes (LABs). AHs compounds were determined on gas chromatography with flame ionization detector (GC-FID), while PAHs and LABs were determined on gas chromatography coupled to a mass spectrometer (GC/MS) in a selected ion mode (SIM). The potential of this dataset is baseline information on hydrocarbons contamination in sediments from a semi-arid region and the bioaccumulation of organic contaminants in marine organisms that can be used as models in ecotoxicological studies.

Few test organisms are employed for sediment toxicity assessments in Tropical regions, including Brazil. We assessed the ability of the clam Anomalocardia flexuosa to respond to contamination in sediment bioassays using dredging materials of a semi-arid region (Ceará State, NE Brazil), with attention to sublethal responses. Sediments were collected during and after dredging (survey 1 and 2, respectively) and animals exposed in laboratory over 28 days, with responses measured at 7 days. Bioaccumulation of contaminants was determined in whole-body soft tissues as a metric of bioavailability, and biomarkers' changes were monitored in terms of enzymes of phase I and II metabolism, acetylcholinesterase (AChE), and antioxidant responses, lipid peroxidation (LPO) and DNA damage (strand breaks). Clams accumulated aliphatic (AHs) and aromatic hydrocarbons (PAHs), and linear alkylbenzenes (LABs) compared to control conditions (day 0), with increased amounts of As, Cd, Cu, and Zn observed in some samples. The enzyme glutathione S-transferase was enhanced in animals exposed to samples, indicating activation of phase II metabolism. Changes observed in glutathione peroxidase (GPx), glutathione reductase (GR), LPO and strand breaks were related to oxidative stress. AChE enzymatic activity also changed, as an indicator of neurotoxicity caused by sediment exposure. The computed integrated biomarker response index (IBR) ranked sites according to the contamination status and proximity to its sources. Correlations found for biomarkers and bioaccumulation of hydrocarbons indicated the influence of harbor activities, effluent discharges, and urban runoff on the sediment pollution of Mucuripe Bay. Data also showed that SQGs are unable to predict bioaccumulation and subchronic effects. Based on our results we consider that biomarkers responses in A. flexuosa are important endpoints to be applied in sediment toxicity bioassays in tropical regions.

It has been suggested that nitric oxide (NO) from iNOS source is involved in inflammation and oxidative stress, and hypertension in obese subjects involves an inflammatory process. However, no study evaluated the participation of iNOS inhibition on cardiovascular, autonomic, and inflammatory parameters in obese rats. Obesity was induced by the administration of 4 mg/g body weight of monosodium glutamate (MSG) or equimolar saline (CTR) in newborn rats. On the 60th day, treatment with aminoguanidine (Amino, 50 mg/kg), an iNOS inhibitor, or 0.9% saline, was started. On the 90th day, mean arterial pressure (MAP) and heart rate (HR) were recorded in conscious rats and autonomic modulation was conducted with the CardioSeries software. Plasma samples were collected to assess lipid peroxidation and prostaglandins (PGE2). In addition, iNOS immunohistochemistry in cardiac tissue was evaluated. MSG rats showed hypertension compared to CTR, and Amino treatment did not reverse it. Obese rats presented increased sympathetic and decreased parasympathetic modulation to the heart, reverted by Amino treatment. Plasma PGE2 was increased in obese rats, and Amino treatment decreased. Obese rats presented increased plasma lipoperoxidation, which was decreased after Amino treatment. Also, cardiac iNOS immunohistochemistry was decreased after Amino treatment. Our data suggest that iNOS activation is involved in the systemic and cardiac mechanisms of oxidative stress, inflammation, and autonomic dysfunction derived from obesity.

Seabirds are very sensitive to environmental changes and due to their large longevity they are also sensitive to cumulative impacts. These birds usually occupy the higher trophic levels. White-chinned petrel (Procellaria aequinoctialis) and black-browed albatross (Thalassarche melanophris) are Procellariiformes, which is a seabird order, composed of 4 families. In the last years, researches are being done and actions are being taken to reduce the mortality of albatrosses and petrels caused by human activities. Due to the great ecological importance of these birds and the developed work with Procellariiformes, this study purpose was to quantify the Br, Cl, Cu, K, Mg, Mn, Na and V elements in white-chinned petrel and black-browed albatross feathers. Bird specimens were killed accidentally by pelagic longline fisheries operating off southern Brazil. Feathers were cleaned with acetone and then milled in a cryogenic mill. Instrumental Neutron Activation Analysis (INAA) was used for quantification of the element concentrations and measurements of induced activities were performed in a High Purity Germanium (HPGe) detector for gamma ray spectrometry. The obtained results on feathers showed that concentrations in these birds are not higher than others studies with the same species and, with exception of Br, there are no significant differences between elements mean concentrations in the two seabirds.

This study aims to analyze factors related to the occurrence of American Tegumentary Leishmaniasis in the Purus Region, based on the reporting of cases between 2001 and 2013, correlating them with livelihoods and subsistence farming in the region, and analyzing them in regards to sex, age, clinical form, occupation, diagnostic methods and seasonality. The analysis parameter which was used included all cases of American Tegumentary Leishmaniasis in each sub-region by municipality. The Purus Region, between the states of Amazonas and Acre, consists of three sub-regions: Upper, Middle, and Lower Purus. We observed that socio-environmental impacts influenced the livelihoods of the human population and that the interaction with extractive activities, especially latex and Brazil nut collecting, where the labor regime implies a long stay in the jungle, leads to socio-environmental conditions that are favorable to the contraction of American Tegumentary Leishmaniasis. During the referred period, there were 13,971 cases of American Tegumentary Leishmaniasis distributed among the sub-regions: High (12611 cases = 90.27%), Middle (1225 cases = 8.77%) and Lower (135 cases = 0.96%). Among the 22 municipalities that were studied, Rio Branco stands out with 31.6% of cases, followed by Xapuri with 12.6% and Sena Madureira with 12.5%. In the results, we highlight the high percentage (20.8%) of mucous forms; the age group from 11 to 50 (70.2%), however, 20.2% were in the age group of 1 month to 10 years of age; cases in males were 69.8%, and, in the reports examined, 43.7%. cited their occupation as extractivism. A statistically significant negative association was demonstrated between cutaneous leishmaniasis and rainfall between Purus municipalities. However, in regards to the association of cutaneous leishmaniasis for both, temperature and Municipal Human Development Index-MHDI, no significant associations were found in Purus. We concluded that American Tegumentary Leishmaniasis occurring in the Purus Region is related to two distinct aspects: the development of enterprises that extend the agricultural frontier, and a change in lifestyle, namely the extraction of wood as an occupation, which has, as a consequence, an environmental impact and creates difficulties in accessing treatment.

Infection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO−/−) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of T. cruzi infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO−/− mice during T. cruzi infection. iNOS inhibition generated a remarkable increase in T. cruzi infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN-γ production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward T. cruzi infection.

Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p ˂ 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p ˂ 0.026) and decreased leptin levels (p ˂ 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE.

Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling. To test this hypothesis, we investigated the antiproliferative and cytotoxic effects of citral on B16F10 murine melanoma cells evaluating its effects on cellular oxidative stress, DNA damage, cell death, and important signaling pathways, as these pathways, namely, extracellular signal-regulated kinases 1/2 (ERK1/2), AKT, and phosphatidylinositol-3 kinase, are involved in cell proliferation and differentiation. The p53 and nuclear factor kappa B were also investigated due to their ability to respond to intracellular stress. We observed that citral exerted antiproliferative and cytotoxic effects in B16F10; induced oxidative stress, DNA lesions, and p53 nuclear translocation; and reduced nitric oxide levels and nuclear factor kappa B, ERK1/2, and AKT. To investigate citral specificity, we used non-neoplastic human and murine cells, HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts), and observed that although citral effects were not specific for cancer cells, non-neoplastic cells were more resistant to citral than B16F10. These findings highlight the potential clinical utility of citral in melanoma, with a mechanism of action involving the oxidative stress generation, nitric oxide depletion, and interference in signaling pathways related to cell proliferation.

Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide dismutase can be involved in the exacerbation of experimental colitis by nonselective nonsteroidal anti-inflammatory drugs.

The study presents an evaluation of potentially toxic elements deposition in Bertioga Channel (Southeastern Brazilian coast) along the last 150 years, the main anthropogenic activity period in the area. Five sediment cores by means of ICP-OES to determine the levels of metals (Cd, Cr, Cu, Ni, Pb and Zn) and As. The pollution load index (PLI) and enrichment factor (EF) were calculated to identify the relative elements toxicity of the sediments and the anthropogenic contribution of the investigated elements. The indexes indicated the absence of contamination but a higher input of As in cores B2 and B5, which have been sampled in an area that presents higher sedimentation rates. Through an statistical analysis of time series decomposition, it was verified that the metals flux to the area follow the cycles of rainy (austral summer and autumn) and dry seasons (austral winter and spring). In conclusion, the enrichment corresponds to the end of the 19th Century, when Santos Harbor was inaugurated, and to the 1970s, when Santos Harbor activities expanded. In addition, the analysis of the indexes and the temporal decomposition indicate that these elements' input to Bertioga Channel is due to natural processes of weathering and sedimentation.

Parasites of the genus Leishmania are capable of inhibiting effector functions of macrophages. These parasites have developed the adaptive ability to escape host defenses; for example, they inactivate the NF-κB complex and suppress iNOS expression in infected macrophages, which are responsible for the production of the major antileishmanial substance nitric oxide (NO), favoring then its replication and successful infection. Metal complexes with NO have been studied as potential compounds for the treatment of certain tropical diseases, such as ruthenium compounds, known to be exogenous NO donors. In the present work, the compound cis-[Ru(bpy)2SO3(NO)]PF6, or RuNO, showed leishmanicidal activity directly and indirectly on promastigote forms of Leishmania (Leishmania) amazonensis. In addition, treatment with RuNO increased NO production by reversing the depletion of NO caused by Leishmania. We also found increased expression of Akt, iNOS, and NF-κB in infected and treated macrophages. These results demonstrated that RuNO was able to kill the parasite by NO release and modulate the transcriptional capacity of the cell.

Green tea (Camellia sinensis) and its main components, the catechins present several biological activities such as: antioxidant and chemoprotective action against hepatotoxic agent as diethylnitrosamine(DEN), a known cytotoxic substance. This work has the objective to evaluate and understand the green tea extract (GTE) mechanisms of action as a chemoprotector agent. Therefore, tests in vivo with Wistar rats using GTE 2% (2mg/100mL) was taken orally as the only source of water for 35 days. To verify the antioxidant and chemoprotective capacity of GTE, DEN (200mg/kg) was used as a lesion agent. The results indicate that green tea if the dosage close to the ones taken by the population is not able to expressively inhibit the lesion caused for the high dose of DEN, but the results indicated a tendency to chemoprotection, suggesting to green tea may act as a prevention substance even in low dosage in presence of a classically known hepatotoxic agent. O chá verde (Camellia sinensis) e seus principais componentes, as catequinas, apresentam várias atividades biológicas, dentre elas a ação antioxidante e quimioprotetora contra agentes hepatotóxicos, como a dietilnitrosamina (DEN), um conhecido agente citotóxico. Este trabalho tem como objetivo avaliar e compreender os mecanismos da ação do extrato do chá verde (ECV), como agente antioxidante e quimioprotetor. Foram realizados testes in vivo com ratos Wistar machos utilizando o ECV a 2% (2mg/100mL) via oral, como única fonte de água, durante 35 dias. Para verificar a capacidade antioxidante e quimioprotetora do ECV utilizou-se a DEN (200mg/kg) como agente lesivo. Os resultados indicam que o chá verde, nas doses próximas as que são ingeridas pela população, não é capaz de inibir significativamente a lesão causada pela alta dose da DEN, mas os resultados indicaram uma tendência à quimioproteção, sugerindo que o chá verde pode agir como substância preventiva mesmo em baixasdoses, frente a um agente hepatotóxico classicamente conhecido.

A presente nota técnica compara o desempenho de duas tecnologias para medição de oxigênio dissolvido (OD) em uso em estações de tratamento de esgoto (ETE): sensores com membrana (eletroquímicos) e com luminescência (ópticos). A precisão na medição da concentração do OD é essencial para o controle de vazão dos aeradores, o que influencia diretamente na eficiência do processo de tratamento e na qualidade do efluente final. Além disso, os aeradores representam até 50% do consumo total de energia elétrica em uma ETE. Os sensores por luminescência apresentam resultados bastante satisfatórios, melhores do que os sensores com membrana. Entretanto recomenda-se um acompanhamento de médio a longo prazo, devido ao seu uso ser muito recente não só no Brasil como no mundo.

OBJETIVO: verificar os efeitos de um programa de caminhada sobre os níveis de autonomia funcional de idosas participantes do Programa Saúde da Família. MÉTODOS: Para este estudo experimental, a amostra foi aleatoriamente dividida em: grupo experimental (GE; n=58, idade:67±6 anos) e grupo controle (GC; n=40; idade:70±6 anos). Todas eram fisicamente ativas, porém sem um rigor na regularidade do programa de atividade física. A autonomia funcional foi avaliada pela bateria de testes do Grupo de Desenvolvimento Latino-Americano para a Maturidade (GDLAM), composta de: caminhar 10m (C10m), levantar-se da posição sentada (LPS), levantar-se da posição de decúbito ventral (LPDV), levantar-se da cadeira e locomover-se pela a casa (LCLC) e o teste de vestir e tirar uma camiseta (VTC). Esses testes resultam no índice de GDLAM (IG). O programa de intervenção foi realizado em frequência semanal de três vezes, com intensidade que variava entre 55% a 75% da frequência cardíaca máxima. RESULTADOS: Na análise intragrupos, pôde-se observar melhora significativa no GE, em todos os testes do GDLAM e no IG (Δ=-4,13; p=0,0001); entretanto, o GC obteve uma piora significativa em todos os testes do GDLAM e no IG (Δ=+0,05; p=0,0001). Na comparação intergrupos, o GE mostrou-se superior ao GC em todos os testes (p

Oxidative stress (OS) is an indispensable condition to ensure genomic instability in cancer cells. In breast cancer (BC), redox alterations have been widely characterized, but since this process results from a chain of inflammatory events, the causal molecular triggers remain to be identified. In this context, we used a microarray approach to investigate the role of the main pro-oxidant transcription factor, nuclear factor-kappa B (NF-κB), in gene profiles of BC subtypes. Our results showed that NF-κB knockdown in distinct BC subtypes led to differential expression of relevant factors involved in glutathione metabolism, prostaglandins, cytochrome P450 and cyclooxygenase, suggesting a relationship between the redox balance and NF-κB in such cells. In addition, we performed biochemical analyses to validate the microarray dataset focusing on OS and correlated these parameters with normal expression or NF-κB inhibition. Our data showed a distinct oxidative status pattern for each of the three studied BC subtype models, consistent with the intrinsic characteristics of each BC subtype. Thus, our findings suggest that NF-κB may represent an additional mechanism related to OS maintenance in BC, operating in various forms to mediate other important predominant signaling components of each BC subtype.

Extending from latitude 34ºS to 22ºS the Southern Brazilian shelf constitutes the only part of the Brazilian shelf with a subtropical to temperate environment. The studies on the different geological aspects of the area began in the 1960's and have recently been reassessed after studies related to the determination of the Economic Exclusive Zone. In terms of morphology, the Southern Brazilian shelf may be divided into three sectors, the São Paulo Bight, the Florianópolis-Mostardas Sector and the Rio Grande Cone, characterized by conspicuous differences in terms of geological determining factors, bathymetry, declivities and the presence of canyons and channels. Despite the existence of hundreds of radiocarbon datings the sea level changes curve of southern Brazil during the Last Glacial Cycle is still a matter of debate. A recent controversy on the Middle and late Holocene sea level changes curve raised the question of the amplitude of the oscillations which occurred in the period. Also, a few but relatively consistent radiocarbon datings suggest the occurrence of a high sea level during Isotope Stage 3. In terms of sedimentary cover the Southern Brazilian shelf exhibits a very strong hydrodynamic control, both latitudinal and bathymetrical. The sector southward from 25ºS is characterized by the influence of the plume of water carrying sediments originating from the Río de La Plata. Actually its presence is conspicuous up to 28ºS, with the area between this latitude and 25ºS constituting a transitional zone. In terms of bathymetry the outer shelf is marked by the "floor-polisher" effect of the Brazil Current, which is responsible for the maintenance of a relict facies in areas deeper than 100 meters.Estendendo-se entre as latitudes 34ºS e 22ºS, a plataforma continental sul-brasileira constitui o único setor que corresponde a um ambiente subtropical a temperado. Os estudos dos diferentes aspectos geológicos da área iniciaram-se na década de 1960 e foram recentemente retomados após os trabalhos relativos à delimitação da Zona Econômica Exclusiva. Em termos de morfologia, pode ser dividida em três setores: Embaiamento de São Paulo, Setor Florianópolis-Mostardas e o Cone do Rio Grande, cada qual definido com base em diferenças geológicas relativas a batimetria, declividade e a presença de cânions e canais. A despeito da existência de centenas de datações ao radiocarbono, a curva de variações relativas do nível do mar no Último Ciclo Glacial é ainda tema de debate. Controvérsia recente sobre as curvas de variação do nível do mar sobre as durante o Holoceno Médio e Tardio trouxe à tona a questão da amplitude das oscilações do nível do mar. Adicionalmente, poucas mas consistentes datações sugerem a ocorrência de um nível do mar elevado durante o Estágio Isotópico 3. Em termos de processos sedimentares atuais, a plataforma continental sul-brasileira exibe um controle hidrodinâmico muito forte, tanto latitudinal quanto batimétrico. O setor ao sul de 25ºS é caracterizado pela influência da pluma de água que carreia sedimentos originários do Rio da Prata, cuja presença é conspícua até 28ºS, havendo uma zona de transição entre essas duas latitudes. A plataforma externa é marcada pelo "efeito enceradeira" da Corrente do Brasil, relíquia responsável pela manutenção de uma fácies em áreas além da isóbata de 100 metros.

The Cananéia-Iguape system, SE Brazil, consists of a complex of lagoonal channels, located in a United Nations Educational, Scientific and Cultural Organization (UNESCO) Biosphere Reserve. Nevertheless, important environmental changes have occurred in approximately the last 150 yrs due to the opening of an artificial channel, the Valo Grande, connecting the Ribeira de Iguape River to the lagoonal system. Our objective is to assess the historical record of the uppermost layers of the sedimentary column of the lagoonal system in order to determine the history of environmental changes caused by the opening of the artificial channel. In this sense, an integrated geochemical-faunal approach is used. The environmental changes led significant modifications in salinity, in changes of the depositional patterns of sediments and foraminiferal assemblages (including periods of defaunation), and, more drastically, in the input of heavy metals to the coastal environment. The concentrations Pb in the core analyzed here were up to two times higher than the values measured in contaminated sediments from the Santos estuary, the most industrialized coastal zone in Brazil.O sistema Cananéia-Iguape (Sudeste do Brasil), consiste em um complexo de canais lagunares localizados no interior de uma Reserva da Biosfera (assim definida pela UNESCO). Não obstante, variações ambientais importantes ocorreram nos últimos 150 anos, devido à abertura de um canal artificial, o Valo Grande, conectando o Rio Ribeira de Iguape ao sistema lagunar. O objetivo deste trabalho foi determinar a história das variações ambientais no sistema lagunar, causadas pela abertura do canal artificial, através da análise das camadas superiores da coluna sedimentar de um testemunho coletado no sistema. Neste sentido, uma abordagem integrada, envolvendo variações geoquímicas e faunísticas foi utilizada. As variações ambientais ocorridas apontam para mudanças drásticas na salinidade, nos padrões de sedimentação, nas associações de foraminíferos (incluindo períodos azóicos) e, mais drasticamente, no aporte de metais para o sistema costeiro. As concentrações de Pb no testemunho coletado indicam valores duas vezes maiores do que os medidos em sedimentos contaminados do estuário de Santos, situado na zona costeira mais industrializada do Brasil.

Walker-256 tumor is a fast-growing tumor and has been studied under several metabolic aspects associated or not to cachexia. It was observed in our laboratory that animals with Walker-256 tumor, after spontaneous death (usually around the fifteenth day), showed significant pulmonary edema with fluid in the pleural cavity. Some studies have suggested that physical training improves the survival of animals with tumor and minimizes the effects of cachexia. The purpose of our work was to assess the pulmonary edema index as well as the cardiac and skeletal muscle mass, besides the survival of rats with Walker-256 tumor submitted previously to physical training through swimming (N). For this study male Wistar rats (200 to 220 g) were used, submitted to physical training through swimming (1 hour; 5 days a week, four weeks). One day after the training, sedentary rats (C) or trained ones (N) were submitted to inoculation on the right flank of 8 x 107 Walker-256 tumor cells (T). Immediately after spontaneous death of these animals, the pulmonary edema index (PEI), cardiac and skeletal muscle mass (gastrocnemius and soleus) were evaluated. Pulmonary edema was evaluated through the index calculated by the relation between lung and body weights of each animal, and multiplied by 100 (PP/PC x 100) (LEE et al., 2001). Muscle mass (MM) index was calculated similarly. In normal animals the PEI is equal to 0,53±0,02 (n=20). In tumor-bearing rats after spontaneous death the PEI was significantly higher (2,62±0,31, n=18). After the physical training in rats without tumor, the PEI was 0,55±0,03 (n=5). Whereas in tumor-bearing rats previously trained, it was obtained a pulmonary edema index lower than that of the control group with tumor (1,46±0,16, n=5; pO tumor Walker-256 é um carcinoma de crescimento rápido e tem sido estudado sob vários aspectos metabólicos, associados ou não, à caquexia. Foi observado, em nosso laboratório, que em animais portadores de tumor Walker-256 após morte espontânea (geralmente em torno do décimo quinto dia) apresentavam edema pulmonar significativo com presença de líquido na cavidade pleural. Alguns trabalhos têm sugerido que o treinamento físico melhora a sobrevida de animais com tumor e minimiza os efeitos da caquexia. O objetivo de nosso trabalho foi o de avaliar o índice de edema pulmonar e massa muscular esquelética e cardíaca, além da sobrevida de ratos portadores de tumor Walker-256 submetidos previamente a treinamento físico por natação (N). Para este estudo, foram usados ratos Wistar machos (200 a 220g), submetidos ao treinamento físico por natação (1 hora; 5 dias/semana, 4 semanas). Um dia após o treinamento, ratos sedentários (C) ou treinados (N) foram submetidos à inoculação no flanco direito de 8 x 107 células de tumor de Walker 256 (T). Imediatamente após a morte espontânea desses animais, foram avaliados o índice de edema pulmonar (IEP), a massa muscular esquelética (gastrocnêmio e soleus) e cardíaca. O edema pulmonar foi avaliado pelo índice calculado pela relação entre os pesos pulmonar e corporal de cada animal, e multiplicada por 100 (PP/PC x 100) (LEE et al., 2001). O índice de massa muscular (IMM) foi calculado de forma similar. Em animais normais, o IEP é igual a 0,53±0,02 (n=20). Em ratos portadores de tumor após a morte espontânea apresentaram IEP significativamente maior (2,62±0,31, n=18). Após o treinamento físico em animais sem tumor, o IEP foi de 0,55±0,03 (n=5). Já em animais portadores de tumor previamente treinados obteve-se um índice de edema inferior ao grupo controle com tumor (1,46±0,16, n=5; p

The fact that drugs currently used in the treatment of Leishmania are highly toxic and associated with acquired resistance has promoted the search for new therapies for treating American tegumentary leishmaniasis (ATL). In this study, BALB/c mice were injected in the hind paw with Leishmania (Leishmania) amazonensis and subsequently treated with a combination of nitric oxide (NO) donor (cis-[Ru(bpy) 2imN(NO)](PF6)3) (Ru-NO), given by intraperitoneal injection, and oral Brazilian propolis for 30 days. Ru-NO reached the center of the lesion and increased the NO level in the injured hind paw without lesion exacerbation. Histological and immunological parameters of chronic inflammation showed that this combined treatment increased the efficacy of macrophages, determined by the decrease in the number of parasitized cells, leading to reduced expression of proinflammatory and tissue damage markers. In addition, these drugs in combination fostered wound healing, enhanced the number of fibroblasts, pro-healing cytokines and induced collagen synthesis at the lesion site. Overall, our findings suggest that the combination of the NO donor Ru-NO and Brazilian propolis alleviates experimental ATL lesions, highlighting a new therapeutic option that can be considered for further in vivo investigations as a candidate for the treatment of cutaneous leishmaniasis.

Leishmania amazonensis (L. amazonensis) infection can cause severe local and diffuse injuries in humans, a condition clinically known as American cutaneous leishmaniasis (ACL). Currently, the therapeutic approach for ACL is based on Glucantime, which shows high toxicity and poor effectiveness. Therefore, ACL remains a neglected disease with limited options for treatment. Herein, the in vitro antiprotozoal effect and mechanisms of the diterpene kaurenoic acid [ent-kaur-16-en-19-oic acid] (KA) against L. amazonensis were investigated. KA exhibited a direct antileishmanial effect on L. amazonensis promastigotes. Importantly, KA also reduced the intracellular number of amastigote forms and percentage of infected peritoneal macrophages of BALB/c mice. Mechanistically, KA treatment reestablished the production of nitric oxide (NO) in a constitutive NO synthase- (cNOS-) dependent manner, subverting the NO-depleting escape mechanism of L. amazonensis. Furthermore, KA induced increased production of IL-1β and expression of the inflammasome-activating component NLRP12. These findings demonstrate the leishmanicidal capability of KA against L. amazonensis in macrophage culture by triggering a NLRP12/IL-1β/cNOS/NO mechanism.

Este texto pretende apresentar as bases da teoria semiótica greimasiana e seus mais recentes desenvolvimentos teóricos. Os conceitos linguísticos propostos por Saussure e Hjelmslev são expostos e também é mostrado o desenvolvimento desses conceitos na semiótica das paixões e na semiótica tensiva. Um texto publicitário é destacado para demonstrar a aplicação da teoria. Esse texto publicitário organiza seu discurso sobre a figura de Jesus Cristo. A noção do poder espiritual de Cristo na sociedade ocidental possibilitou o entendimento e a integração dos valores internos e externos no conceito de homem. Os valores divergentes do eu e do outro – conceitos fundamentais no desenvolvimento do pensamento humano – são conciliados na noção de compaixão e martírio cristãos. É na ideia da compaixão de Cristo que o eu e o outro compartilham um espaço de valores comuns. Mas, nas representações contemporâneas da figura de Cristo, os valores cristãos-sacros se atenuam enquanto evolui uma estética da imagem de Cristo com outros valores integrados. A figura de Cristo continua reconhecível, mas o sagrado martírio deixa de ser um discurso central na contemporaneidade. Os símbolos e figuras religiosos e políticos são elementos fundamentais no campo cultural e as mudanças nos valores relacionados a essas figuras refletem (e refratam) mudanças na organização social.

Michael Gravett and colleagues review the burden of pregnancy-related infections, especially in low- and middle-income countries, and offer suggestions for a more effective intervention strategy. [ABSTRACT FROM AUTHOR]

Introduction: This is the first of seven articles from a preterm birth and stillbirth report. Presented here is an overview of the burden, an assessment of the quality of current estimates, review of trends, and recommendations to improve data.Preterm Birth: Few countries have reliable national preterm birth prevalence data. Globally, an estimated 13 million babies are born before 37 completed weeks of gestation annually. Rates are generally highest in low- and middle-income countries, and increasing in some middle- and high-income countries, particularly the Americas. Preterm birth is the leading direct cause of neonatal death (27%); more than one million preterm newborns die annually. Preterm birth is also the dominant risk factor for neonatal mortality, particularly for deaths due to infections. Long-term impairment is an increasing issue.Stillbirth: Stillbirths are currently not included in Millennium Development Goal tracking and remain invisible in global policies. For international comparisons, stillbirths include late fetal deaths weighing more than 1000g or occurring after 28 weeks gestation. Only about 2% of all stillbirths are counted through vital registration and global estimates are based on household surveys or modelling. Two global estimation exercises reached a similar estimate of around three million annually; 99% occur in low- and middle-income countries. One million stillbirths occur during birth. Global stillbirth cause-of-death estimates are impeded by multiple, complex classification systems.Recommendations To Improve Data: (1) increase the capture and quality of pregnancy outcome data through household surveys, the main data source for countries with 75% of the global burden; (2) increase compliance with standard definitions of gestational age and stillbirth in routine data collection systems; (3) strengthen existing data collection mechanisms--especially vital registration and facility data--by instituting a standard death certificate for stillbirth and neonatal death linked to revised International Classification of Diseases coding; (4) validate a simple, standardized classification system for stillbirth cause-of-death; and (5) improve systems and tools to capture acute morbidity and long-term impairment outcomes following preterm birth.Conclusion: Lack of adequate data hampers visibility, effective policies, and research. Immediate opportunities exist to improve data tracking and reduce the burden of preterm birth and stillbirth. [ABSTRACT FROM AUTHOR]

ABSTRACT: In this paper, we present new evidence regarding a Marine Isotope Stage 3 (MIS3) transgression on the south-eastern Brazilian coast (Baixada Santista coastal plain). Data collected from a Standard Penetration Test (SPT) drilling reveal the occurrence of myxohaline sediments between cal BP 45,000 and 41,000. A deeper sequence, which shows a clear transition from terrestrial to a myxohaline environment, was associated with MIS5e. Organic and inorganic proxies have been used to recognize the variations on the terrestrial/myxohaline/marine deposits, as well as to infer about climate and energy of the depositional environment. Environmental change, which could correspond to a sea-level peak or the occurrence of drier conditions, was recognized between 43,000 and 42,000 cal BP. The results reinforce the need for future works on MIS3 variability on the South American Atlantic coast.

JUSTIFICATIVA E OBJETIVOS: A dor pós-operatória em pacientes obesos é um evento prejudicial para sua recuperação, retardando a alta e aumentando a chance de complicações. O objetivo deste estudo foi determinar a frequência de dor na sala de recuperação pós-anestésica e averiguar os fatores associados à ocorrência de dor moderada ou intensa em obesos submetidos a gastroplastia, relacionando-os a possíveis complicações. MÉTODOS: Estudo observacional prospectivo incluindo 84 pacientes submetidos a anestesia geral com sevoflurano para gastroplastia laparoscópica. Na sala de recuperação pós-anestésica, os pacientes foram avaliados quanto à intensidade da dor pela escala numérica e verbal, sedação (escala de Ramsay), ocorrência de náuseas, vômitos e complicações respiratórias. O modelo de regressão logística foi utilizado para determinar as variáveis independentes associadas à dor. RESULTADOS: Na sala de recuperação pós-anestésica, a ausência de dor na admissão ocorreu em 61,63% dos pacientes. Na análise multivariada, o uso do opioide fentanil em comparação ao sufentanil foi o único fator independentemente associado à dor (RR 3,07 - IC95% 1,17-6,4). Não houve diferença entre o tipo de opioide utilizado e a ocorrência de náuseas e vômitos (p>0,05). Os escores da escala de Ramsay não diferiram entre os tipos de opioides utilizados no intraoperatório (p>0,05). CONCLUSÃO: O único fator independentemente associado à dor na sala de recuperação pós-anestésica foi o tipo de opioide utilizado na indução anestésica. A dor pós-operatória ainda é um evento frequente que acomete a maioria dos pacientes e protocolos de analgesia precisam ser implementados para minimizar os efeitos que a dor subtratada pode causar.

Uma única dose de DDT (diclorodifiniltricloroetano) (50 e I00mg/kg) aumentou a atividade metabolizadora de drogas em fígado de ratos. A N-desmetilação da aminopirina aumentou 3 a 4 vezes quando comparada com o controle. Por outro lado, um aumento de 2 vezes foi verificado tanto para a hidroxilação da anilina, como nos níveis de citocromo P4So- O tempo de hipnose barbitúrica provocado pelo pentobarbital sádico foi reduzido em 80% nas duas doses empregadas. Nossos resultados demonstraram que o efeito indutor máximo foi atingido com a dose de 50 mg/kg de DDT. Além disso, revelaram também que DDT exerce um efeito diferencial, na sua capacidade indutora, sobre a atividade da aminopirina N-desmetilase e anilina hidroxilase.

The microbiome of the female reproductive tract has implications for women's reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or European ancestry case-matched for race, gestational age and household income; and a longitudinally sampled cohort of 90 pregnant women of African or non-African ancestry. In these women, the vaginal microbiome shifted during pregnancy toward Lactobacillus-dominated profiles at the expense of taxa often associated with vaginal dysbiosis. The shifts occurred early in pregnancy, followed predictable patterns, were associated with simplification of the metabolic capacity of the microbiome and were significant only in women of African or Hispanic ancestry. Both genomic and environmental factors are likely contributors to these trends, with socioeconomic status as a likely environmental influence.

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.

Background: Survivors of infant group B streptococcal (GBS) disease are at risk of neurodevelopmental impairment (NDI), a burden not previously systematically quantified. This is the 10th of 11 articles estimating the burden of GBS disease. Here we aimed to estimate NDI in survivors of infant GBS disease., Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data on the risk of NDI after invasive GBS disease in infants <90 days of age. We did meta-analyses to derive pooled estimates of the percentage of infants with NDI following GBS meningitis., Results: We identified 6127 studies, of which 18 met eligibility criteria, all from middle- or high-income contexts. All 18 studies followed up survivors of GBS meningitis; only 5 of these studies also followed up survivors of GBS sepsis and were too few to pool in a meta-analysis. Of meningitis survivors, 32% (95% CI, 25%-38%) had NDI at 18 months of follow-up, including 18% (95% CI, 13%-22%) with moderate to severe NDI., Conclusions: GBS meningitis is an important risk factor for moderate to severe NDI, affecting around 1 in 5 survivors. However, data are limited, and we were unable to estimate NDI after GBS sepsis. Comparability of studies is difficult due to methodological differences including variability in timing of clinical reviews and assessment tools. Follow-up of clinical cases and standardization of methods are essential to fully quantify the total burden of NDI associated with GBS disease, and inform program priorities., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0-6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS., Methods: We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage., Results: We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%-1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0-.9)., Conclusions: The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%-2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Improving maternal, newborn, and child health is central to Sustainable Development Goal targets for 2030, requiring acceleration especially to prevent 5.6 million deaths around the time of birth. Infections contribute to this burden, but etiological data are limited. Group B Streptococcus (GBS) is an important perinatal pathogen, although previously focus has been primarily on liveborn children, especially early-onset disease. In this first of an 11-article supplement, we discuss the following: (1) Why estimate the worldwide burden of GBS disease? (2) What outcomes of GBS in pregnancy should be included? (3) What data and epidemiological parameters are required? (4) What methods and models can be used to transparently estimate this burden of GBS? (5) What are the challenges with available data? and (6) How can estimates address data gaps to better inform GBS interventions including maternal immunization? We review all available GBS data worldwide, including maternal GBS colonization, risk of neonatal disease (with/without intrapartum antibiotic prophylaxis), maternal GBS disease, neonatal/infant GBS disease, and subsequent impairment, plus GBS-associated stillbirth, preterm birth, and neonatal encephalopathy. We summarize our methods for searches, meta-analyses, and modeling including a compartmental model. Our approach is consistent with the World Health Organization (WHO) Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER), published in The Lancet and the Public Library of Science (PLoS). We aim to address priority epidemiological gaps highlighted by WHO to inform potential maternal vaccination., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Intrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide., Methods: We identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated)., Results: We received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle-income, 14 of 20 (70%) upper-middle-income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle-income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%-95%); for clinical risk factor-based screening, coverage was 29% (range, 10%-50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar., Conclusions: There is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global prevention of GBS disease., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis in high-income contexts, despite declines due to intrapartum antibiotic prophylaxis (IAP). Recent evidence suggests higher incidence in Africa, where IAP is rare. We investigated the global incidence of infant invasive GBS disease and the associated serotypes, updating previous estimates., Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data regarding invasive GBS disease in infants aged 0-89 days. We conducted random-effects meta-analyses of incidence, case fatality risk (CFR), and serotype prevalence., Results: We identified 135 studies with data on incidence (n = 90), CFR (n = 64), or serotype (n = 45). The pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% confidence interval [CI], .43-.56), and was highest in Africa (1.12) and lowest in Asia (0.30). Early-onset disease incidence was 0.41 (95% CI, .36-.47); late-onset disease incidence was 0.26 (95% CI, .21-.30). CFR was 8.4% (95% CI, 6.6%-10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V., Conclusions: The incidence of infant GBS disease remains high in some regions, particularly Africa. We likely underestimated incidence in some contexts, due to limitations in case ascertainment and specimen collection and processing. Burden in Asia requires further investigation., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: There are an estimated 2.6 million stillbirths each year, many of which are due to infections, especially in low- and middle-income contexts. This paper, the eighth in a series on the burden of group B streptococcal (GBS) disease, aims to estimate the percentage of stillbirths associated with GBS disease., Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Literatura Latino-Americana e do Caribe em Ciências da Saúde, World Health Organization Library Information System, and Scopus) and sought unpublished data from investigator groups. Studies were included if they reported original data on stillbirths (predominantly ≥28 weeks' gestation or ≥1000 g, with GBS isolated from a sterile site) as a percentage of total stillbirths. We did meta-analyses to derive pooled estimates of the percentage of GBS-associated stillbirths, regionally and worldwide for recent datasets., Results: We included 14 studies from any period, 5 with recent data (after 2000). There were no data from Asia. We estimated that 1% (95% confidence interval [CI], 0-2%) of all stillbirths in developed countries and 4% (95% CI, 2%-6%) in Africa were associated with GBS., Conclusions: GBS is likely an important cause of stillbirth, especially in Africa. However, data are limited in terms of geographic spread, with no data from Asia, and cases worldwide are probably underestimated due to incomplete case ascertainment. More data, using standardized, systematic methods, are critical, particularly from low- and middle-income contexts where the highest burden of stillbirths occurs. These data are essential to inform interventions, such as maternal GBS vaccination., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)