50 years of the water-flow variance in Tucuruí reservoir related with Brazilian energy consumption.

Dammed rivers lose its natural characteristics of the flow cycle and becomes controlled by the energy demands of the hydroelectric plants. With the connection of the energy-producing plants to a central station in Brazil the situation is aggravated since demands in different regions of the country affect the water flow. Using downstream flow data from the Tucuruí dam over a 50-year period, we tested whether the variation in water flow has changed. We observed an increase of the annual variation of the water flow and the extreme events of flooding at downstream of the dam, indicating the operation of the dam intensified the control of water passage. The study reveals an increase in the variation of water flow in the dam's downstream section following the interconnection of the Tucurui dam with the Central System in 1997. Management strategies for the dam should be considered integrated with the national electricity demand, since distant demands may affect the local environment in question.

Factors associated with non-completion of latent tuberculosis infection treatment in Rio de Janeiro, Brazil: A non-matched case control study.

INTRODUCTION: There are scarce data on the routine latent tuberculosis infection treatment (LTBIT) and factors associated with a non-completion in high tuberculosis burden countries. Therefore, in this study we aimed to evaluate the factors associated with non-completion of LTBIT. MATERIALS AND METHODS: This was a non-matched case control study conducted at a University Hospital in Rio de Janeiro, Brazil. A total of 114 cases and 404 controls were enrolled between January/1999 and December/2009. Cases were close contacts who did not complete the LTBIT and controls were the contacts that completed it. Multivariate analysis was used to investigate risk factors associated with non-completion of LTBIT among contacts in two different periods of recruitment. RESULTS: Factors associated with non-completion LTBIT included: drug use (OR 23.33, 95% CI 1.83-296.1), TB treatment default by the index case (OR 16.97, 95% CI 3.63-79.24) and drug intolerance. TB disease rates after two years of follow up varied from 0.4% to 1.9%. The number necessary to treat to prevent one TB case among contacts was 116. CONCLUSIONS: Non-completion treatment by the index case and illicit drug use were associated with not completing latent tuberculosis infection treatment and no tuberculosis disease was identified among those who completed latent tuberculosis infection treatment.

Criteria for progressive fibrotic hypersensitivity pneumonitis in a Portuguese patient cohort.

Background: Hypersensitivity pneumonitis (HP) is a syndrome caused by sensitisation to inhaled antigens that leads to an abnormal immune response in the airways and lung parenchyma. Some patients previously diagnosed with certain types of fibrotic interstitial lung diseases (f-ILDs), including fibrotic HP (f-HP), are susceptible to develop a progressive fibrosing phenotype (PF-ILD), despite initial state-of-the-art management. Objectives: To characterise a cohort of patients with a multidisciplinary diagnosis (MTD) of chronic f-HP, who were followed up in an ILD outpatient clinic of a hospital in Portugal, and to assess the prevalence of PF-ILD criteria in these patients. Methods: Data were collected from all patients with a definite or provisional diagnosis of f-HP after a multidisciplinary team discussion. Patients were followed up between December 2014 and July 2019. Data included clinical characteristics, high-resolution chest tomography (HRCT) disease patterns, lung function tests, bronchoalveolar lavage and further immunological work-up, biopsy reports (conventional transbronchial lung biopsy, transbronchial lung cryobiopsy or surgical video-assisted thoracoscopic lung biopsy), all ILD multidisciplinary team records and diagnostic confidence levels. Patients were assessed according to PF-ILD criteria as defined in the INBUILD trial. Results: We identified 83 patients with an MTD of HP, who had been followed up for at least 12 months. Of these, 63 (75.9%) were diagnosed with f-HP. Of the 63 f-HP patients, 33.3% (n=21) fulfilled the predefined criteria for PF-HP: 66.7% had a relative decline of ≥10% forced vital capacity (FVC); 5% a relative decline of 5 - 9% FVC, with worsening symptoms or increased fibrosis on HRCT; and 23.8% had worsening respiratory symptoms with radiological progression. Conclusion: This single-centre cohort study demonstrated that a third of f-HP patients presented with PF-ILD, as determined by progression during initial standard-of-care treatment. A usual interstitial pneumonia (UIP)/UIP-like pattern was present in >70% of patients with f-HP, and two-thirds of these patients had an FVC decline of ≥10%. PF-HP patients were also more exacerbation prone. According to recent trial data, this segment of patients can be considered possible candidates for antifibrotic treatment, with a reasonable prospect of effectiveness. Further efforts should focus on refining knowledge of longitudinal behaviour of large multicentric cohorts of f-HP patients, establishing a consensual and uniform definition of progression for use in clinical practice, as well as developing prognostic prediction tools to better (and early) inform the disease course.

What do asthmatic patients think about telemedicine visits?

Summary: Introduction. Due to the Coronavirus disease 2019 (COVID-19) outbreak and the national emergency state, virtual visits were implemented as an alternative to in-person visits. With this study we aimed to establish asthma patients' general satisfaction with the quality of health care provided by virtual visits (phone or video calls). Materials and methods. A questionnaire (9 questions) was published on the Facebook page of the Portuguese Association of Asthmatics. It was available online for general self-reported asthmatic patients to answer during one month, starting on 11st May 2020. The survey only allowed one answer per registered user. Results. Fifty-five responses were obtained. Patients were satisfied with communication with providers (> 88%); nevertheless, one-half evaluated the virtual visit as inferior when compared to in-person visits. About one third attributed a classification of 6 or less (0-10 scale, 0 being the worst and 10 the best consultation possible), but still most of the patients would either recommend it or use this kind of medical visits in the future, even outside the actual pandemic context. Patients also referred some important limitations, as lack of physical examination and the fact that the medical visit was more impersonal. Only 27% had technical issues accessing virtual visits. Positive aspects were also named, such as virtual visits being practical and avoiding the need to move to the hospital. Discussion and conclusions. Our survey revealed that small changes could further increase patients' satisfaction, adherence and confidence in telemedicine. Although presenting some limitations, virtual visits seem to be generally well accepted by asthmatic patients and it might be a good alternative for in-person visits, at leastin such difficult times when social distancing is recommended.

Entomopathogenic Viruses in the Neotropics: Current Status and Recently Discovered Species.

The market for biological control of insect pests in the world and in Brazil has grown in recent years due to the unwanted ecological and human health impacts of chemical insecticides. Therefore, research on biological control agents for pest management has also increased. For instance, insect viruses have been used to protect crops and forests around the world for decades. Among insect viruses, the baculoviruses are the most studied and used viral biocontrol agent. More than 700 species of insects have been found to be naturally infected by baculoviruses, with 90% isolated from lepidopteran insects. In this review, some basic aspects of baculovirus infection in vivo and in vitro infection, gene content, viral replication will be discussed. Furthermore, we provide examples of the use of insect viruses for biological pest control and recently characterized baculoviruses in Brazil.

Congenital Zika syndrome is associated with maternal protein malnutrition.

Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.

Identification of Zika virus in immature phases of Aedes aegypti and Aedes albopictus: a surveillance strategy for outbreak anticipation.

A progressive increase in the circulation of arboviruses in tropical countries has been observed, accounting for 700,000 yearly deaths in the world. The main objective of this article was to identify the presence of Zika (ZIKV), dengue (DENV), and Chikungunya (CHIKV) viruses in immature stages of Aedes aegypti and Ae. albopictus. Household collections of immature phases of the vectors were carried out in the years 2015 and 2016. A total of 2902 dwellings were visited and the rate of infestation with larvae and pupae of Aedes mosquitoes was 283/1462 (19.4%) in March 2015 and 55/1440 (3.8%) in June 2015. In March 2015, 907 larvae/pupae were collected (583 or 64.3% of Ae. aegypti and 324 or 35.7% of Ae. albopictus) while in June 2015 there was a reduction in the number of immature forms found: 197 larvae/pupae (121 or 61.4% of Ae. aegypti and 76 or 38.6% of Ae. albopictus). This reduction was accompanied by a decrease in suspected human ZIKV cases from March to June 2015. The RT-qPCR performed in 18 pools identified that three (two of Ae. aegypti and one of Ae. albopictus) were positive for ZIKV, and none were positive for DENV or CHIKV. Our findings demonstrated that ZIKV was present in immature stages of insect vectors in the study region at least five months prior to the peak of ZIKV associated cases. Xenomonitoring of immature phases of the vectors may prove useful for predicting outbreaks.

Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil.

BACKGROUND: Vertical transmission of Zika virus (ZIKV) is associated with congenital malformations but the mechanism of pathogenesis remains unclear. Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted a case-control study in a cohort of Brazilian women infected with ZIKV during pregnancy. METHODS: A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV infection, 28 were classified as cases and 24 as controls based on the presence or absence of CZS in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of CZS. RESULTS: From the 817 single nucleotide variations (SNVs) included in association analyses, 22 SNVs in 17 genes were associated with CZS under an additive model (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3 and ADCY7 genes showed the most prominent effect. The association of ADCY3 and ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (P < 0.002). CONCLUSION: These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity and influence the outcome of CZS, being promising candidates for further replication studies and functional analysis.

Identification of Zika virus in immature phases of Aedes aegypti and Aedes albopictus: a surveillance strategy for outbreak anticipation

A progressive increase in the circulation of arboviruses in tropical countries has been observed, accounting for 700,000 yearly deaths in the world. The main objective of this article was to identify the presence of Zika (ZIKV), dengue (DENV), and Chikungunya (CHIKV) viruses in immature stages of Aedes aegypti and Ae. albopictus. Household collections of immature phases of the vectors were carried out in the years 2015 and 2016. A total of 2902 dwellings were visited and the rate of infestation with larvae and pupae of Aedes mosquitoes was 283/1462 (19.4%) in March 2015 and 55/1440 (3.8%) in June 2015. In March 2015, 907 larvae/pupae were collected (583 or 64.3% of Ae. aegypti and 324 or 35.7% of Ae. albopictus) while in June 2015 there was a reduction in the number of immature forms found: 197 larvae/pupae (121 or 61.4% of Ae. aegypti and 76 or 38.6% of Ae. albopictus). This reduction was accompanied by a decrease in suspected human ZIKV cases from March to June 2015. The RT-qPCR performed in 18 pools identified that three (two of Ae. aegypti and one of Ae. albopictus) were positive for ZIKV, and none were positive for DENV or CHIKV. Our findings demonstrated that ZIKV was present in immature stages of insect vectors in the study region at least five months prior to the peak of ZIKV associated cases. Xenomonitoring of immature phases of the vectors may prove useful for predicting outbreaks.

Genomic and epidemiological monitoring of yellow fever virus transmission potential.

The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.

Acute kidney injury in kidney transplant patients.

Managing kidney transplant patients in an acute medical unit can be challenging, as patients have a single functioning kidney, underlying chronic kidney disease, and are immunosuppressed. Transplant patients develop AKI for all usual reasons but the differential diagnosis is wider and includes specific problems, such as obstruction of a single functioning kidney, vascular thrombosis, rejection, drug toxicity and drug-induced thrombotic microangiopathy. Septic AKI is common but again, the differential diagnosis of sepsis is wider. Transplant patients are at higher risk of developing both community and opportunistic infections, especially in the first year after the transplant or after any increase in immunosuppressive medication. In addition, there is always a risk of rejection, especially in case of reduction of immunosuppressive medications. Therefore, any change in the immunosuppressive therapy should to be discussed with the transplant team to achieve an appropriate balance between avoiding rejection and preventing opportunistic infections.

Pediatric eosinophilic esophagitis in Portugal.

SUMMARY: Eosinophilic esophagitis (EoE) is an increasingly frequent diagnosis in our clinical practice, mainly in pediatric age. Allergic responses to food and aeroallergens have been increasingly implicated in the etiology of this disease. We describe a retrospective data analysis of pediatric EoE patients followed in our Immunoallergology Department. Of the 25 children (22 male, average 10.8 years), 88% had prior history of rhinoconjunctivitis, 76% asthma, 48% eczema and 36% food allergy. After evaluation, we identified in 76% and 92% of patients food and aeroallergen sensitization, respectively; 68% had simultaneously food and inhalant sensitization and 96% had at least one positive test to aeroallergens or food allergens. The first (44%) and the most frequent (56%) symptom was dysphagia. The time between symptoms onset and the EoE diagnosis averaged 18.6 ± 29.4 months. A multidisciplinary approach is needed for a correct evaluation, intervention and follow-up of these patients.

Use of Rituximab in Systemic Lupus Erythematosus: A Single Center Experience Over 14 Years.

OBJECTIVE: To describe the clinical outcome and safety of rituximab (RTX) treatment in systemic lupus erythematosus (SLE) patients with severe manifestations or whose disease is refractory to standard immunosuppressive therapy, treated at a single center. METHODS: This was a retrospective analysis of all patients with SLE treated with RTX at 1 center between June 2000 and December 2013. The clinical outcome was assessed by determining British Isles Lupus Assessment Group (BILAG) scores and anti-double-stranded DNA (anti-dsDNA) and C3 levels before and 6 months after RTX treatment. For safety analysis, adverse events and deaths were recorded. RESULTS: Of a total of 115 patients, 93.9% were female, the mean ± SD age at diagnosis was 26.39 ± 11.90 years, and the mean ± SD disease duration at first RTX treatment was 91.96 ± 84.80 months. A BILAG score variation of -11.26 ± 11.38 (P < 0.001) was recorded 6 months after the first RTX treatment; 40% of patients had a complete response and 27% had a partial response; in 36.5% of patients, C3 levels increased more than 25%, and in 33.5% anti-dsDNA levels decreased more than 50%. Depletion of CD19+ cells was achieved in 94.0% of patients. Hypogammaglobulinemia was detected in 14.9% of patients, with significant reduction for IgM (P < 0.001) and IgG (P = 0.001) levels. Severe infections, infusion-related reactions, and hypersensitivity reactions occurred in 7%, 3.5%, and 2.6% of patients, respectively. Of the 115 patients, 62 patients had repeated RTX treatments, with an average number of 1.95 ± 1.17 cycles per patient and a mean ± SD interval between infusions of 21.44 ± 20.11 months. At the end of followup, 11 patients were deceased; 6 had cardiovascular events. CONCLUSION: RTX treatment was effective in decreasing disease activity, with a low incidence of adverse effects.

High-intensity Interval Training in the Boundaries of the Severe Domain: Effects on Sprint and Endurance Performance.

In order to compare the effects of two 4-week interval training programs performed at the lower (Critical Power, CP) or at the higher (The highest intensity at which V˙O2max is attained, IHIGH) intensities of the severe exercise domain on sprint and endurance cycling performance, 21 recreationally trained cyclists performed the Wingate Anaerobic Test (WAnT) and a 250-kJ time trial. Accumulated oxygen deficit (AOD), surface electromyography (RMS), and blood lactate kinetics were measured during the WAnT. Subjects were assigned to 105% CP or IHIGH groups. During the WAnT, significantly greater improvements in peak (Mean ±95%CI) (5.7±2.3% vs. 0.2±2.2%), mean power output (MPO) (3.7±2.0% vs. 0.5±1.8%), and RMS (17.8±7.4% vs. -15.7±7.9%) were observed in the IHIGH group (P<0.05). Higher and lower AOD, respectively, at the start and during the second half of the WAnT were observed after IHIGH training. The changes in RMS and MPO induced by the training were significantly correlated (r=0.584). The 2 interventions induced improvements in the 250-kJ time trial. In conclusion, although the improvements in endurance performance were similar, training at IHIGH led to higher gains in WAnT performance than training at 105%CP.

miRQuest: integration of tools on a Web server for microRNA research.

This report describes the miRQuest - a novel middleware available in a Web server that allows the end user to do the miRNA research in a user-friendly way. It is known that there are many prediction tools for microRNA (miRNA) identification that use different programming languages and methods to realize this task. It is difficult to understand each tool and apply it to diverse datasets and organisms available for miRNA analysis. miRQuest can easily be used by biologists and researchers with limited experience with bioinformatics. We built it using the middleware architecture on a Web platform for miRNA research that performs two main functions: i) integration of different miRNA prediction tools for miRNA identification in a user-friendly environment; and ii) comparison of these prediction tools. In both cases, the user provides sequences (in FASTA format) as an input set for the analysis and comparisons. All the tools were selected on the basis of a survey of the literature on the available tools for miRNA prediction. As results, three different cases of use of the tools are also described, where one is the miRNA identification analysis in 30 different species. Finally, miRQuest seems to be a novel and useful tool; and it is freely available for both benchmarking and miRNA identification at http://mirquest.integrativebioinformatics.me/.

MicroRNA-124 links p53 to the NF-κB pathway in B-cell lymphomas.

The contribution of microRNAs to lymphoma biology is not fully understood. In particular, it remains untested whether microRNA dysregulation could contribute to the emergence of the aggressive subset of B-cell lymphomas that coexpress MYC and BCL2. Here, we identify microRNA-124 (miR-124) as a negative regulator of MYC and BCL2 expression in B-cell lymphomas. Concordantly, stable or transient ectopic expression of miR-124 suppressed cell proliferation and survival, whereas genetic inhibition of this miRNA enhanced the fitness of these tumors. Mechanistically, the activities of miR-124 towards MYC and BCL2 intersect with both oncogenic and tumor-suppressive pathways. In respect to the former, we show that miR-124 directly targets nuclear factor-κB (NF-κB) p65, and using genetic approaches, we demonstrate that this interaction accounts for the miR-124-mediated suppression of MYC and BCL2. We also characterized miR-124 promoter region and identified a functional p53 binding site. In agreement with this finding, endogenous or ectopic expression of wild-type, but not mutant, p53 increased miR-124 levels and suppressed p65, MYC and BCL2. Our data unveil an miRNA-dependent regulatory circuitry that links p53 to the NF-κB pathway, which when disrupted in B-cell lymphoma may be associated with aberrant coexpression of MYC and BCL2 and poor prognosis.