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Laine de Carvalho Guerra Pessoa Mamede,1 Rafaela Lira Formiga Cavalcanti de Lima,2 Alexandre Sérgio Silva,1 João Carlos Lima Rodrigues Pita,3 Nadjeanny Ingrid Galdino Gomes,1 Elisama Araújo de Sena,1 Rhayra Priscila Moraes Nobrega,2 João Otávio Scarano Alcântara,2 Julie Hanna Fontes de Souza,2 Glêbia Alexa Cardoso,3 José Luiz de Brito Alves,1 Maria da Conceição Rodrigues Gonçalves1 1Post-Graduate Program in Nutrition Sciences, Health Sciences Center, Federal University of Paraíba, João Pessoa, Brazil; 2Department of Nutrition, Health Sciences Center, Federal University of Paraíba, João Pessoa, Brazil; 3Health Sciences Center, Federal University of Paraíba, João Pessoa, BrazilCorrespondence: Laine de Carvalho Guerra Pessoa MamedeDepartment of Nutrition, Health Sciences Center, Universidade Federal da Paraíba, Campus I – Jd, Cidade Universitária, João Pessoa, PB, CEP: 58051-900, BrazilTel/Fax +55 83 9 91089818Email laineguerramamede@gmail.comAim: The study aimed to evaluate the effects of vitamin D3 (VD3) supplementation on inflammation and oxidative stress markers in overweight and obese women with deficiency or insufficiency of vitamin D.Methods: Twenty-nine overweight or obese women who had a deficiency or insufficiency of vitamin D were placed into two groups according to VD3 intervention. Patients in the supplemented group received a single oral megadose of VD3 (VD3, n=14). Patients in placebo group received a single oral identical capsule without vitamin D (placebo, n = 15). Anthropometric and biochemical variables were assessed at baseline and after 4-weeks intervention.Results: Anthropometric variables (waist circumference, waist–hip ratio, waist–height ratio and body mass index) were similar between groups (p > 0.05). VD3 supplementation increased the serum levels of 25-hydroxyvitamin D (p=0.000), malondialdehyde (p=0.021) and C-reactive protein (p=0.043) in overweight and obese women. Additionally, VD3 supplementation reduced the serum levels of aspartate aminotransferase (AST, p=0.035), alanine aminotransferase (ALT, p< 0.0001) in overweight and obese women. Despite this, the serum levels of parathyroid hormone (PTH), fasting glucose (FG), and alpha-1- acid glycoprotein (A1GPA), total antioxidant capacity (TAC) were similar between groups.Conclusion: In summary, a single oral megadose of VD3 increased 25-hydroxyvitamin D serum levels but did not improve oxidative stress and inflammation markers.Keywords: vitamin D, obesity, inflammation, lipid peroxidation

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Potential breeding containers for Aedes aegypti and Aedes albopictus mosquitoes are found in different environments, these places are considered by the National Dengue Control Program in Brazil as strategic points (SP), which have favorable conditions for the development of those insects. The aim of this study is to identify potential breeding containers for A. aegypti and A. albopictus at strategic points in the city of Codó, Maranhão. This study was conducted in five districts, one in each administrative area of the city. A survey of the types and quantity of existing strategic points in each neighborhood was carried out, and surveys of these properties were carried out to inspect the potential breeding containers, with the collection of the vectors' number of immatures found at them. 125 properties were inspected of which 76.91% and 81.25% were vacant lots in the dry and rainy seasons, respectively. There was a difference between the median of the different strategic points (H = 21.96; p < 0.0001), For A. aegypti, there was no difference between the medians of number of immatures regarding the strategic points (H = 3.71; p = 0.28). The total number of immature A. albopictus was higher in vacant lots than in workshops (H = 9.41; p = 0.02, p < 0.05). 4,356 and 4,911 potential breeding containers were found in the dry and rainy seasons, respectively. Regarding the potential breeding containers, 7 (0.16%) and 47 (0.96%) were found with immature vectors, in the dry and rainy seasons, respectively. There were more positive containers in the rainy season for which there was a difference between the median of the number of mosquitoes per positive container (H = 15.66; p = 0.01), the number of immatures for the tires group was greater than Vases and Fixed groups (p < 0.05); the same result was observed in the analyses of the species in the separate form. The impressive number of potential breeding containers found in the SP in both seasons highlights the importance of developing control strategies for these vectors, with emphasis on places such as vacant lots, workshops, tire shops and junkyards, which are serving as dispersal urban sites of vectors.

Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac 2-26 for analysis. In addition, the effect of Ac 2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease., Competing Interests: VC, MS, JH, CB, CQ, MG, JC, TG, GL, JB, IP, CM, TM, KB, RM, MO, MA, LS, DS, HS, MT No competing interests declared, MP is on the Scientific Advisory Board of ResoTher Pharma AS, which is interested in developing Annexin A1-derived peptides for cardiovascular settings, (© 2022, Costa et al.)

Background: The use of the 3D printer in complex cardiac surgery planning., Objectives: To analyze the use and benefits of 3D printing in heart valve surgery through a systematic review of the literature., Methods: This systematic review was reported following the Preferred Reporting Items for Systematic Review and registered in the Prospero (International Prospective Register of Systematic Reviews) database under the number CRD42017059034. We used the following databases: PubMed, EMBASE, Scopus, Web of Science and Lilacs. We included articles about the keywords "Heart Valves", "Heart Valve Prosthesis Implantation", "Heart Valve Prosthesis", "Printing, Three-Dimensional", and related entry terms. Two reviewers independently conducted data extraction and a third reviewer solved disagreements. All tables used for data extraction are available at a separate website. We used the Cochrane Collaboration tool to assess the risk of bias of the studies included., Results: We identified 301 articles and 13 case reports and case series that met the inclusion criteria. Our studies included 34 patients aged from 3 months to 94 years., Conclusions: Up to the present time, there are no studies including a considerable number of patients. A 3D-printed model produced based on the patient enables the surgeon to plan the surgical procedure and choose the best material, size, format, and thickness to be used. This planning leads to reduced surgery time, exposure, and consequently, lower risk of infection.

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are important arthropod-borne viruses from the Flaviviridae family. DENV is a global public health problem with significant social and economic impacts, especially in tropical and subtropical areas. JEV is a neurotropic arbovirus endemic to east and southeast Asia. There are no U.S. FDA-approved antiviral drugs available to treat or to prevent DENV and JEV infections, leaving nearly one-third of the world's population at risk for infection. Therefore, it is crucial to discover potent antiviral agents against these viruses. Nucleoside analogs, as a class, are widely used for the treatment of viral infections. In this study, we discovered nucleoside analogs that possess potent and selective anti-JEV and anti-DENV activities across all serotypes in cell-based assay systems. Both viruses were susceptible to sugar-substituted 2'- C -methyl analogs with either cytosine or 7-deaza-7-fluoro-adenine nucleobases. Mouse studies confirmed the anti-DENV activity of these nucleoside analogs. Molecular models were assembled for DENV serotype 2 (DENV-2) and JEV RNA-dependent RNA polymerase replication complexes bound to nucleotide inhibitors. These models show similarities between JEV and DENV-2, which recognize the same nucleotide inhibitors. Collectively, our findings provide promising compounds and a structural rationale for the development of direct-acting antiviral agents with dual activity against JEV and DENV infections., (Copyright © 2019 American Society for Microbiology.)

Aims: To compare the dosage of radiation the thyroid and gonad glands receive in pediatric patients undergoing chest X-rays, in distinct positions, towards the goal of developing of an X-ray tube positioning protocol., Methods: A randomized controlled clinical trial was carried out in the Pediatric Intensive Care Unit (PICU) at the Institute of Cardiology/University Foundation of Cardiology of Rio Grande do Sul, Brazil from June 2014 to September 2016. Patients were divided into two groups. One group was positioned with the thyroid gland facing the anode end of an X-ray tube, and in the other group the thyroid gland faced the cathode end. Radiographs were evaluated by five observers, following criteria recommended by the Commission of the European Communities (CEC)., Results: Forty-eight pediatric patients, with a mean age of 2.0 ± 1.3 years, participated in this study. Based on the evaluation of 48 images, it was determined that the thyroid and gonad glands facing the cathode were exposed to 13.3 ± 3.1 μGy and 13.5 ± 4.1 μGy of radiation, respectively ( p  = 0.008). Additionally, the thyroid and gonad glands facing the anode were exposed to 11.7 ± 3.1 μGy and 12.7 ± 3.1 μGy of radiation, respectively ( p  = 0.007). The mean input dose in the center of the chest was 20.8 ± 9.6 μGy in both positions., Discussion: The proximity of the thyroid gland to the cathode end of the X-ray tube appears to be related to the dosage of ionizing radiation. Adverse effects associated with exposure to ionizing radiation could be minimized by positioning the thyroid gland to the anodic end of the X-ray tube., Conclusion: Patients should be placed facing the anode end of the X-ray tube when taking thoracic X-rays, in order to reduce radiation exposure to the thyroid and gonad glands.ClinicalTrials.gov Identifier: NCT02925936.

The PI3K pathway is frequently hyperactivated in primary T-cell acute lymphoblastic leukemia (T-ALL) cells. Activation of the PI3K pathway has been suggested as one mechanism of glucocorticoid resistance in T-ALL, and patients harboring mutations in the PI3K negative regulator PTEN may be at increased risk of induction failure and relapse. By gene expression microarray analysis of T-ALL cells treated with the PI3K inhibitor AS605240, we identified Myc as a prominent downstream target of the PI3K pathway. A significant association was found between the AS605240 gene expression signature and that of glucocorticoid resistance and relapse in T-ALL. AS605240 showed anti-leukemic activity and strong synergism with glucocorticoids both in vitro and in a NOD/SCID xenograft model of T-ALL. In contrast, PI3K inhibition showed antagonism with methotrexate and daunorubicin, drugs that preferentially target dividing cells. This antagonistic interaction, however, could be circumvented by the use of correct drug scheduling schemes. Our data indicate the potential benefits and difficulties for the incorporation of PI3K inhibitors in T-ALL therapy.

Dengue virus (DENV) is the most prevalent arbovirus in the world, found mainly in tropical regions. As clinical manifestations present frequently as nonspecific febrile illness, laboratory diagnosis is essential to confirm DENV infections and for epidemiological studies. Recombinant envelope (E) antigens of four serotypes of DENV were used to develop an immunoglobulin G enzyme-linked immunosorbent assay (IgG-ELISA). To evaluate the IgG-ELISA, a panel of serum samples that had been tested previously by a plaque reduction neutralization test (PRNT) was investigated for the presence of anti-E antibodies against the four DENV serotypes. IgG-ELISA was found to have a sensitivity (91%) and specificity (98%) at a receiver-operating characteristic (ROC) optimized cutoff and demonstrated high performance as well as good indexes. A concordance of 97% was achieved between both assays, and only 21/704 (3%) samples were not concordant. The results of the present study demonstrate a moderate correlation between neutralizing antibody titers and IgG-ELISA values. These findings indicate that the recombinant protein-based IgG-ELISA is a suitable method for routine serodiagnosis, monitoring and seroepidemiological studies of DENV infections., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The enrichment analysis is a standard procedure to interpret 'omics' experiments that generate large gene lists as outputs, such as transcriptomics and protemics. However, despite the huge success of enrichment analysis in these classes of experiments, there is a surprising lack of application of this methodology to survey other categories of large-scale biological data available. Here, we report Kegg Orthology enrichMent-Online DetectiOn (KOMODO), a web tool to systematically investigate groups of monophyletic genomes in order to detect significantly enriched groups of homologous genes in one taxon when compared with another. The results are displayed in their proper biochemical roles in a visual, explorative way, allowing users to easily formulate and investigate biological hypotheses regarding the taxonomical distribution of genomic elements. We validated KOMODO by analyzing portions of central carbon metabolism in two taxa extensively studied regarding their carbon metabolism profile (Enterobacteriaceae family and Lactobacillales order). Most enzymatic activities significantly biased were related to known key metabolic traits in these taxa, such as the distinct fates of pyruvate (the known tendency of lactate production in Lactobacillales and its complete oxidation in Enterobacteriaceae), demonstrating that KOMODO could detect biologically meaningful differences in the frequencies of shared genomic elements among taxa. KOMODO is freely available at http://komodotool.org.

Vaccinia virus strains from the family Poxviridae have been frequently isolated in Brazil and associated with outbreaks of exanthematic disease affecting cows and humans. An ELISA IgG was applied to evaluate the seroprevalence of orthopoxviruses in a community located in a rural settlement in the Amazon region, where no orthopoxvirus outbreaks have yet been reported. An overall seroprevalence of 27.89% was found, and it was 23.38% in the non-vaccinated population (smallpox vaccination). These results strongly suggest that orthopoxviruses circulate in this population, and it is the first finding of seropositivity for orthopoxviruses in a population without any previously reported outbreaks.

Background: Despite the fact that smallpox eradication was declared by the World Health Organization (WHO) in 1980, other poxviruses have emerged and re-emerged, with significant public health and economic impacts. Vaccinia virus (VACV), a poxvirus used during the WHO smallpox vaccination campaign, has been involved in zoonotic infections in Brazilian rural areas (Bovine Vaccinia outbreaks - BV), affecting dairy cattle and milkers. Little is known about VACV's natural hosts and its epidemiological and ecological characteristics. Although VACV was isolated and/or serologically detected in Brazilian wild animals, the link between wildlife and farms has not yet been elucidated., Methodology/principal Findings: In this study, we describe for the first time, to our knowledge, the isolation of a VACV (Mariana virus - MARV) from a mouse during a BV outbreak. Genetic data, in association with biological assays, showed that this isolate was the same etiological agent causing exanthematic lesions observed in the cattle and human inhabitants of a particular BV-affected area. Phylogenetic analysis grouped MARV with other VACV isolated during BV outbreaks., Conclusion/significance: These data provide new biological and epidemiological information on VACV and lead to an interesting question: could peridomestic rodents be the link between wildlife and BV outbreaks?

Objectives: Sedation scores are important tools for use in pediatric intensive care units. The Comfort-Behavior scale is a valid method for the assessment of children although it is considered an extensive scale. The motor activity assessment scale is validated for an adult population. We considered it simpler then the one above and suitable for application in children. None of these scores had been translated into Portuguese. Our objective was to apply both scales in Portuguese to a pediatric population under mechanical ventilation. Secondary objectives were to evaluate the sedation level of children on mechanical ventilation in tertiary pediatric intensive care units and to compare the Comfort- Behavior and motor activity assessment scales in this population., Methods: After translating the scales into Portuguese, both were simultaneously applied to 26 patients by 2 pediatricians. Each scale was applied 116 times in total., Results: The intraclass correlation coefficient was 0.90 (0.85 - 0.93 CI 95%) for the Comfort-Behavior and 0.94 (0.92 - 0.96 CI 95%) for the motor activity assessment scale. When applying the Comfort-Behavior scale, the Crombach's alpha was 0.81 for observer A and 0.92 for observer B. The Spearman coefficient was 0.86 for observer A and 0.91 for observer B. These patients were found to be deeply sedated, showing low values in both scales., Conclusions: The scales were successfully translated into Portuguese and both were adequate to assess pain and sedation in the pediatric population under mechanical ventilation. Sedation level was high in this sample of applications.