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FioAntar, FIOCRUZ's research project in Antarctica, is based on the One Health approach. FioAntar aims to generate relevant information that will help reduce the risk of future pandemics and improve the search for chemical compounds and new biological molecules. After four expeditions to Antarctica under the scope of PROANTAR, Fiocruz has identified Influenza H11N2 virus in environmental fecal samples, as well as Histoplasma capsulatum and Bacillus cereus in soil samples. In addition, in a prospective virome analysis from different lakes in the South Shetland Islands, six viral orders were described, supporting future research related to the biodiversity and viral ecology in this extreme ecosystem. Our findings of environmental pathogens of public health importance are a warning about the urgency of establishing a surveillance agenda on zoonoses in Antarctica due to the imminent risks that ongoing environmental and climate changes impose on human health across the planet. FioAntar strives to establish a comprehensive surveillance program across Antarctica, monitoring circulation of pathogens with the potential to transcend continent boundaries, thereby mitigating potential spread. For Fiocruz, Antarctica signifies a new frontier, teeming with opportunities to explore novel techniques, refine established methodologies, and cultivate invaluable knowledge.

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Technology in electric vehicles has increased substantially in the past decade. Moreover, it is projected to grow at record highs in the coming years since these vehicles are needed to reduce the contamination related to the transportation sector. One of the essential elements of an electric car is its battery, due to its cost. Batteries comprise parallel and series-connected cell arrangements to meet the power system requirements. Therefore, they require a cell equalizer circuit to preserve their safety and correct operation. These circuits keep a specific variable of all cells, such as the voltage, within a particular range. Within cell equalizers, capacitor-based ones are very common as they have many desirable characteristics of the ideal equalizer. In this work, an equalizer based on the switched-capacitor is proposed. A switch is added to this technology that allows the disconnection of the capacitor from the circuit. In this way, an equalization process can be achieved without excess transfers. Therefore, a more efficient and faster process can be completed. In addition, it allows another equalization variable to be used, such as the state of charge. This paper studies the operation, power design, and controller design of the converter. Moreover, the proposed equalizer was compared to other capacitor-based architectures. Finally, simulation results were presented to validate the theoretical analysis.

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La hipertensión arterial pulmonar se caracteriza por una presión arterial pulmonar media y resistencia vascular pulmonar elevadas y remodelado patológico de las arterias pulmonares. La entrada de calcio desde el espacio extracelular al intracelular a través de canales dependientes e independientes de voltaje juega un rol fundamental en el aumento de la contractilidad de las arterias pulmonares y la pérdida de regulación del comportamiento proliferativo de las células de las distintas capas de la pared de las arterias pulmonares. De esta manera, estos canales contribuyen con la vasoconstricción exacerbada de las arterias pulmonares y a su remodelado patológico. El objetivo de esta revisión es recapitular la evidencia obtenida desde modelos celulares y animales respecto a la contribución de los principales canales de calcio de membrana plasmática en estos mecanismos fisiopatológicos claves en el desarrollo de la hipertensión pulmonar, discutiendo su valor potencial como diana farmacológica para terapias presentes y futuras.

Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.

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Moderate and late preterm newborns comprise around 85% of live births < 37 weeks gestation. Data on their neonatal mortality in middle-income countries is limited. This study aims to analyze the temporal trend, causes and timing of neonatal mortality of infants with 320/7-366/7 weeks gestation without congenital anomalies from 2004-2015 in the population of São Paulo State, Brazil. A database was built by deterministic linkage of birth and death certificates. Causes of death were classified by ICD-10 codes. Among 7,317,611 live births in the period, there were 545,606 infants with 320/7-366/7 weeks gestation without congenital anomalies, and 5782 of them died between 0 and 27 days. The neonatal mortality rate decreased from 16.4 in 2004 to 7.6 per thousand live births in 2015 (7.47% annual decrease by Prais-Winsten model). Perinatal asphyxia, respiratory disorders and infections were responsible, respectively, for 14%, 27% and 44% of the 5782 deaths. Median time to death was 24, 53 and 168 h, respectively, for perinatal asphyxia, respiratory disorders, and infections. Bottlenecks in perinatal health care are probably associated with the results that indicate the need for policies to reduce preventable neonatal deaths of moderate and late preterm infants in the most developed state of Brazil.

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Antarctic camps pose psychophysiological challenges related to isolated, confined, and extreme (ICE) conditions, including meals composed of sealed food. ICE conditions can influence the microbiome and inflammatory responses. Seven expeditioners took part in a 7-week Antarctic summer camp (Nelson Island) and were evaluated at Pre-Camp (i.e., at the beginning of the ship travel), Camp-Initial (i.e., 4th and 5th day in camp), Camp-Middle (i.e., 19th-20th, and 33rd-34th days), Camp-Final (i.e., 45th-46th day), and at the Post-Camp (on the ship). At the Pre-Camp, Camp-Initial, and Camp-Final, we assessed microbiome and inflammatory markers. Catecholamines were accessed Pre- and Post-Camp. Heart rate variability (HRV), leptin, thyroid stimulating hormone (TSH), and thyroxine (T4) were accessed at all time points. Students' t-tests or repeated-measures analysis of variance (one or two-way ANOVA) followed by Student-Newman-Keuls (post hoc) were used for parametric analysis. Kruskal-Wallis test was applied for non-parametric analysis. Microbiome analysis showed a predominance of Pseudomonadota (34.01%), Bacillota (29.82%), and Bacteroidota (18.54%), followed by Actinomycetota (5.85%), and Fusobacteria (5.74%). Staying in a long-term Antarctic camp resulted in microbiome fluctuations with a reduction in Pseudomonadota-a "microbial signature" of disease. However, the pro-inflammatory marker leptin and IL-8 tended to increase, and the angiogenic factor VEGF was reduced during camp. These results suggest that distinct Antarctic natural environments and behavioral factors modulate oral microbiome and inflammation.

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Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.

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The Antarctic continent is one of the most inhospitable places on earth, where living creatures, mostly represented by microorganisms, have specific physiological characteristics that allow them to adapt to the extreme environmental conditions. These physiological adaptations can result in the production of unique secondary metabolites with potential biotechnological applications. The current study presents a genetic and antibacterial characterization of four Antarctic fungi isolated from soil samples collected in Pedro Vicente Maldonado Scientific Station, at Fort William Point, Greenwich Island, Antarctica. Based on the sequences of the internal transcribed spacer (ITS) region, the fungi were identified as Antarctomyces sp., Thelebolus sp., Penicillium sp., and Cryptococcus gilvescens. The antibacterial activity was assessed against four clinical bacterial strains: Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Staphylococcus aureus, by a modified bacterial growth inhibition assay on agar plates. Results showed that C. gilvescens and Penicillium sp. have potential antibiotic activity against all bacterial strains. Interestingly, Thelebolus sp. showed potential antibiotic activity only against E. coli. In contrast, Antarctomyces sp. did not show antibiotic activity against any of the bacteria tested under our experimental conditions. This study highlights the importance of conservation of Antarctica as a source of metabolites with important biomedical applications.

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Neonatal pulmonary hypertension (NPHT) is produced by sustained pulmonary vasoconstriction and increased vascular remodeling. Soluble guanylyl cyclase (sGC) participates in signaling pathways that induce vascular vasodilation and reduce vascular remodeling. However, when sGC is oxidized and/or loses its heme group, it does not respond to nitric oxide (NO), losing its vasodilating effects. sGC protein expression and function is reduced in hypertensive neonatal lambs. Currently, NPHT is treated with NO inhalation therapy; however, new treatments are needed for improved outcomes. We used Cinaciguat (BAY-582667), which activates oxidized and/or without heme group sGC in pulmonary hypertensive lambs studied at 3,600 m. Our study included 6 Cinaciguat-treated (35 ug kg-1 day-1 x 7 days) and 6 Control neonates. We measured acute and chronic basal cardiovascular variables in pulmonary and systemic circulation, cardiovascular variables during a superimposed episode of acute hypoxia, remodeling of pulmonary arteries and changes in the right ventricle weight, vasoactive functions in small pulmonary arteries, and expression of NO-sGC-cGMP signaling pathway proteins involved in vasodilation. We observed a decrease in pulmonary arterial pressure and vascular resistance during the acute treatment. In contrast, the pulmonary pressure did not change in the chronic study due to increased cardiac output, resulting in lower pulmonary vascular resistance in the last 2 days of chronic study. The latter may have had a role in decreasing right ventricular hypertrophy, although the direct effect of Cinaciguat on the heart should also be considered. During acute hypoxia, the pulmonary vascular resistance remained low compared to the Control lambs. We observed a higher lung artery density, accompanied by reduced smooth muscle and adventitia layers in the pulmonary arteries. Additionally, vasodilator function was increased, and vasoconstrictor function was decreased, with modifications in the expression of proteins linked to pulmonary vasodilation, consistent with low pulmonary vascular resistance. In summary, Cinaciguat, an activator of sGC, induces cardiopulmonary modifications in chronically hypoxic and pulmonary hypertensive newborn lambs. Therefore, Cinaciguat is a potential therapeutic tool for reducing pulmonary vascular remodeling and/or right ventricular hypertrophy in pulmonary arterial hypertension syndrome.

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Open-water diving in a polar environment is a psychophysiological challenge to the human organism. We evaluated the effect of short-term diving (i.e., 10 min) in Antarctic waters on autonomic cardiac control, thyroid hormone concentration, body temperatures, mood, and neuropsychological responses (working memory and sleepiness). Data collection was carried out at baseline, before, and after diving in four individuals divided into the supporting (n=2) and diving (n=2) groups. In the latter group, autonomic cardiac control (by measuring heart rate variability) was also assessed during diving. Diving decreased thyroid-stimulating hormone (effect size = 1.6) and thyroxine (effect size = 2.1) concentrations; these responses were not observed for the supporting group. Diving also reduced both the parasympathetic (effect size = 2.6) and sympathetic activities to the heart (ES > 3.0). Besides, diving reduced auricular (effect size > 3.0), skin [i.e., hand (effect size = 1.2) and face (effect size = 1.5)] temperatures compared to pre-dive and reduced sleepiness state (effect size = 1.3) compared to basal, without changing performance in the working memory test. In conclusion, short-term diving in icy waters affects the hypothalamic-pituitary-thyroid axis, modulates autonomic cardiac control, and reduces body temperature, which seems to decrease sleepiness.

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Objetivo: Avaliar o perfil das internações por insuficiência cardíaca (IC) na cidade de Anápolis/GO. Métodos: Os dados foram obtidos no DATASUS, referentes ao período de agosto/2016 a agosto/2019. Foram avaliados: a incidência de internações hospitalares gerais e por IC, a média de permanência, a mortalidade e o custo hospitalar, estratificados por sexo, faixa etária. Resultados: No período estudado, ocorreram 6773 internações hospitalares por doenças do aparelho circulatório, sendo 14,6% por IC (994 internações em números absolutos). Pacientes do sexo masculino corresponderam a 51,85%. A média de permanência global foi de 8,1 dias. A taxa de mortalidade esteve em ascensão, iniciando com 15,52% em 2016 e chegando a 23,86% em 2019. O custo da AIH média aumentou de R$ 1.831,99 em 2016 para R$ 2.406,88 em 2019 (aumento de 31,3%). Conclusão: a Insuficiência Cardíaca é uma síndrome de elevado custo para o Sistema Único de Saúde, e existe a necessidade de conscientização por parte do poder público municipal para este problema saúde.

Objective: To evaluate the profile of patients hospitalized for heart failure (HF) in the city of Anápolis, state of Goiás, Brazil. Methods: Data were obtained from the Brazilian Unified Health System Database (DATASUS) from August 2016 to August 2019. We evaluated the incidence of general and HF hospitalizations, mean length of stay, mortality, and hospital costs. The data were stratified by sex and age group. Results: In the study period, there were 6,773 hospitalizations due to circulatory system diseases, 14.6% of which were due to HF (994 hospitalizations in absolute numbers). Male patients accounted for 51.85% of the sample. Overall mean length of stay was 8.1 days. The mortality rate increased from 15.52% in 2016 to 23.86% in 2019. Mean inpatient hospital authorization costs increased from R$ 1,831.99 in 2016 to R$ 2,406.88 in 2019 (31.3% increase). Conclusions: HF is a costly disease for the Brazilian Unified Health System, and the municipal government should raise awareness of this health problem.

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BACKGROUND: Fetal chronic hypoxia is associated with blood flow redistribution and oxidative damage in the brain, leading to increased perinatal morbimortality. Melatonin reduces oxidative stress, improves vascular function, and has neuroprotective effects. OBJECTIVES: This study aimed to determine the effects of an oral melatonin treatment to pregnant ewes at high-altitude, on the cerebrovascular function of their neonates. STUDY DESIGN: Ten high-altitude pregnant sheep received either vehicle or melatonin (10 mg/d) during the last third of gestation until delivery. Postnatal daily hemodynamic measurements were recorded from lambs until 12 days old. In addition, lambs were submitted to a graded oxygenation protocol to assess cerebrovascular responses. Subsequently, lambs were euthanized, and middle cerebral arteries (MCA) were collected for vascular function, protein levels, and morphostructural analyses. RESULTS: Antenatal treatment doubled plasma levels of melatonin in pregnant ewes. Melatonin increased carotid flow and decreased carotid vascular resistance in the lambs by the end of the first week. Furthermore, melatonin increased MCA's maximal vasoconstrictor and vasodilator responses, associated with nitric oxide-dependent and independent mechanisms. CONCLUSIONS: An oral treatment with melatonin during pregnancy promotes postnatal cerebral perfusion in chronically hypoxic neonates. Melatonin is a potential treatment for cerebrovascular dysfunction due to perinatal chronic hypoxia.

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The family Characidae is the most diverse group of fishes in the Neotropics with challenging systematics. The three genera Carlana, Parastremma, and Rhoadsia, formerly considered the subfamily Rhoadsiinae, are now included in the subfamily Stethaprioninae. Previous phylogenetic analyses did not include all genera of Rhoadsiinae, specifically Parastremma. Here, we estimated the phylogenetic relationships and divergence times of the genera of Rhoadsiinae (the Rhoadsia clade) relative to the most representative genera of the Characidae. We used six molecular markers from the mitochondrial and nuclear genome to estimate the phylogeny and divergence times. We confirmed the monophyly of the Rhoadsia clade. Furthermore, we estimated that the Central American genus Carlana and the western Colombian genus Parastremma diverged approximately 13 Mya (95% HPD 8.36­18.11), consistent with the early-closure estimates of the Isthmus of Panama (~15 Mya). The genus Rhoadsia, endemic to Western Ecuador and Northern Peru, was estimated to originate at around 20 Mya (95% HPD 14.35­25.43), consistent with the Andean uplift (~20 Mya).(AU)

La familia Characidae es el grupo más diverso de peces en el Neotrópico con una sistemática compleja. Los tres géneros Carlana, Parastremma y Rhoadsia, antes considerados en la subfamilia Rhoadsiinae, ahora se consideran dentro de la subfamilia Stethaprioninae. Los análisis filogenéticos publicados no incluyen todos los géneros de Rhoadsiinae, específicamente Parastremma. Aquí, estimamos las relaciones filogenéticas y los tiempos de divergencia de los géneros de Rhoadsiinae (el clado Rhoadsia) en relación con los géneros más representativos de Characidae. Utilizamos seis marcadores moleculares del genoma mitocondrial y nuclear para estimar la filogenia y el tiempo de divergencia. Confirmamos la monofilia del clado Rhoadsia. Además, estimamos que el género centroamericano Carlana y el género colombiano occidental Parastremma divergieron aproximadamente hace 13 millones de años (95% HPD 8.36­18.11), lo que es consistente con recientes estimaciones del cierre del Istmo de Panamá (~15 millones de años). Se estimó que el género Rhoadsia, endémico del oeste de Ecuador y el norte de Perú, se originó hace alrededor de 20 millones de años (95% HPD 14.35­25.43), consistente con el levantamiento de los Andes (~20 millones de años).(AU)

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Pulmonary arterial hypertension of newborns (PAHN) constitutes a critical condition involving both severe cardiac remodeling and right ventricle dysfunction. One main cause of this condition is perinatal hypoxia and oxidative stress. Thus, it is a public health concern for populations living above 2500 m and in cases of intrauterine chronic hypoxia in lowlands. Still, pulmonary and cardiac impairments in PAHN lack effective treatments. Previously we have shown the beneficial effects of neonatal melatonin treatment on pulmonary circulation. However, the cardiac effects of this treatment are unknown. In this study, we assessed whether melatonin improves cardiac function and modulates right ventricle (RV) oxidative stress. Ten lambs were gestated, born, and raised at 3600 m. Lambs were divided in two groups. One received daily vehicle as control, and another received daily melatonin (1 mg·kg-1·d-1) for 21 days. Daily cardiovascular measurements were recorded and, at 29 days old, cardiac tissue was collected. Melatonin decreased pulmonary arterial pressure at the end of the experimental period. In addition, melatonin enhanced manganese superoxide dismutase and catalase (CAT) expression, while increasing CAT activity in RV. This was associated with a decrease in superoxide anion generation at the mitochondria and NADPH oxidases in RV. Finally, these effects were associated with a marked decrease of oxidative stress markers in RV. These findings support the cardioprotective effects of an oral administration of melatonin in newborns that suffer from developmental chronic hypoxia.

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The authors previously demonstrated that newborn llama (NBLL) express high levels of α1 adrenergic receptors, which provide a potent vasoconstriction response when compared with newborn sheep (NBSH) gestated at sea level. However, data regarding the impact of chronic gestational hypobaric hypoxia on α-adrenergic vasoconstriction in the neonatal life has not been studied. We evaluated if gestation under chronic hypobaric hypoxia modifies α1-adrenergic vasoconstrictor function in NBLL and NBSH. We compared the vasoconstrictor response induced by potassium and α-adrenergic stimuli in isolated small femoral arteries of NBLL and NBSH gestated at high altitude (HA; 3,600 m) or low altitude (LA; 580 m). The maximal contraction (R MAX) and potency (EC50) to potassium, noradrenaline (NA), and phenylephrine (PHE) were larger in HA-NBLL than LA-NBLL. R MAX to potassium, NA, and PHE were lower in HA-NBSH when compared with LA-NBSH and potency results were similar. Competitive blockade with prazosin showed that RNLL LA/HA have a similar pA2. In contrast, NBSH had increased pA2 values in HA when compared with LA. Finally, small femoral arteries denudated or treated with LNAME in LA and HA lacked NO or endothelium participation in response to PHE stimulation. In contrast, NBSH displayed that denudation or blockade with LNAME support NO or endothelium participation in response to PHE activation. In conclusion, HA chronic hypoxia enhances α1 adrenergic receptor activity in small femoral arteries in NBLL to a higher degree than NBSH, implying a higher vasoconstriction function.

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Background: In Brazil, secondary data for epidemiology are largely available. However, they are insufficiently prepared for use in research, even when it comes to structured data since they were often designed for other purposes. To date, few publications focus on the process of preparing secondary data. The present findings can help in orienting future research projects that are based on secondary data. Objective: Describe the steps in the process of ensuring the adequacy of a secondary data set for a specific use and to identify the challenges of this process. Methods: The present study is qualitative and reports methodological issues about secondary data use. The study material was comprised of 6,059,454 live births and 73,735 infant death records from 2004 to 2013 of children whose mothers resided in the State of São Paulo - Brazil. The challenges and description of the procedures to ensure data adequacy were undertaken in 6 steps: (1) problem understanding, (2) resource planning, (3) data understanding, (4) data preparation, (5) data validation and (6) data distribution. For each step, procedures, and challenges encountered, and the actions to cope with them and partial results were described. To identify the most labor-intensive tasks in this process, the steps were assessed by adding the number of procedures, challenges, and coping actions. The highest values were assumed to indicate the most critical steps. Results: In total, 22 procedures and 23 actions were needed to deal with the 27 challenges encountered along the process of ensuring the adequacy of the study material for the intended use. The final product was an organized database for a historical cohort study suitable for the intended use. Data understanding and data preparation were identified as the most critical steps, accounting for about 70% of the challenges observed for data using. Conclusion: Significant challenges were encountered in the process of ensuring the adequacy of secondary health data for research use, mainly in the data understanding and data preparation steps. The use of the described steps to approach structured secondary data and the knowledge of the potential challenges along the process may contribute to planning health research.

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Freshwater fish communities in Ecuador exhibit some of the highest levels of diversity and endemism in the Neotropics. Unfortunately, aquatic ecosystems in the country are under serious threat and conditions are deteriorating. In 2018-19, the government of Ecuador sponsored a series of workshops to examine the conservation status of Ecuador's freshwater fishes. Concerns were identified for 35 species, most of which are native to the Amazon region, and overfishing of Amazonian pimelodid catfishes emerged as a major issue. However, much of the information needed to make decisions across fish groups and regions was not available, hindering the process and highlighting the need for a review of the conservation threats to Ecuador's freshwater fishes. Here, we review how the physical alteration of rivers, deforestation, wetland and floodplain degradation, agricultural and urban water pollution, mining, oil extraction, dams, overfishing, introduced species and climate change are affecting freshwater fishes in Ecuador. Although many of these factors affect fishes throughout the Neotropics, the lack of data on Ecuadorian fish communities is staggering and highlights the urgent need for more research. We also make recommendations, including the need for proper enforcement of existing environmental laws, restoration of degraded aquatic ecosystems, establishment of a national monitoring system for freshwater ecosystems, investment in research to fill gaps in knowledge, and encouragement of public engagement in citizen science and conservation efforts. Freshwater fishes are an important component of the cultural and biological legacy of the Ecuadorian people. Conserving them for future generations is critical.

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The life cycles of many parasitic nematodes include terrestrial gastropods as intermediate hosts. Over the past few decades, a number of cases of parasitism between molluscs and medically-important nematodes have been reported in Brazil, in particular, those involving the invasive giant African gastropod, Achatina fulica, and zoonoses caused by the nematodes Angiostrongylus cantonensis and Angiostrongylus costaricensis, the etiological agents of neuroangiostrongyliasis and abdominal angiostrongyliasis, respectively. In the present study, larvae found infecting A. fulica, Latipes erinaceus, and Thaumastus taunaisii, from two localities in the Brazilian state of Rio de Janeiro were characterized using light and scanning electron microscopy, and sequences of the 18S rRNA and MT-CO1 genes. Genetic markers allowed to identify the larvae collected in the present study as Cruzia tentaculata, whose adults parasitize didelphid marsupials in the Americas. These findings indicate that both native and non-native gastropods may act as intermediate hosts and represent a previously unnoticed heteroxenous life cycle of C. tentaculata.

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Pulmonary arterial hypertension of the newborn (PAHN) is a syndrome caused by chronic hypoxia, characterized by decreased vasodilator function, a marked vasoconstrictor activity, proliferation of smooth muscle cells (SMC) and thickening of the extracellular matrix in the pulmonary circulation, among other characteristics. Prostaglandins are derived from the arachidonic acid (AA) metabolism and are important regulators of pulmonary vascular tone. Since hypoxia induces oxidative stress and has been related to PAHN, a postnatal treatment with melatonin has been proposed due to its antioxidant properties. Here, we determined the effects of melatonin on pulmonary vascular homeostasis given by prostanoids. Ten PAHN newborn lambs were divided in two groups and treated either with vehicle or melatonin. After 1 week of treatment, we assessed pulmonary vascular prostanoids function and expression by wire myography, RT-PCR, Western Blot and immunohistochemistry. Melatonin improved in vivo and ex vivo pulmonary vasodilation. This was associated with an increased function and expression of vasodilator prostanoids at the expense of vasoconstrictor prostanoids. Our study demonstrates for the first time that melatonin may enhance the vasodilator prostanoid pathway in PAHN.

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BACKGROUND: Population-based studies analyzing neonatal deaths in middle-income countries may contribute to design interventions to achieve the Sustainable Development Goals, established by United Nations. This study goal is to analyze the annual trend of neonatal mortality in São Paulo State, Brazil, over a 10-year period and its underlying causes and to identify maternal and neonatal characteristics at birth associated with neonatal mortality. METHOD: A population-based study of births and deaths from 0 to 27 days between 2004 and 2013 in São Paulo State, Brazil, was performed. The annual trend of neonatal mortality rate according to gestational age was analyzed by Poisson or by Negative Binomial Regression models. Basic causes of neonatal death were classified according to ICD-10. Association of maternal demographic variables (block 1), prenatal and delivery care variables (block 2), and neonatal characteristics at birth (block 3) with neonatal mortality was evaluated by Poisson regression analysis adjusted by year of birth. RESULTS: Among 6,056,883 live births in São Paulo State during the study period, 48,309 died from 0 to 27 days (neonatal mortality rate: 8.0/1,000 live births). For the whole group and for infants with gestational age 22-27, 28-31, 32-36, 37-41 and ≥ 42 weeks, reduction of neonatal mortality rate was, respectively, 18 %, 15 %, 38 %, 53 %, 31 %, and 58 %. Median time until 50 % of deaths occurred was 3 days. Main basic causes of death were respiratory disorders (25 %), malformations (20 %), infections (17 %), and perinatal asphyxia (7 %). Variables independently associated with neonatal deaths were maternal schooling, prenatal care, parity, newborn sex, 1st minute Apgar, and malformations. Cesarean delivery, compared to vaginal, was protective against neonatal mortality for infants at 22-31 weeks, but it was a risk factor for those with 32-41 weeks. CONCLUSIONS: Despite the significant decrease in neonatal mortality rate over the 10-year period in São Paulo State, improved access to qualified health care is needed in order to avoid preventable neonatal deaths and increase survival of infants that need more complex levels of assistance.

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