Bosentan attenuates sickle cell disease erythrocyte HbS polymerization and impaired deformability induced by endothelin-1.

The effects of endothelin-1 (ET-1) on erythrocytes from sickle cell disease (SCD) patients have been described, but mechanisms of ET-1 regarding primary erythrocyte functions remain unknown. ET-1 is a vasoconstrictor peptide produced by endothelial cells, and the expression of ET-1 is increased in SCD. The present study used ex vivo experiments with sickle cell erythrocytes, ET-1, and bosentan, a dual antagonist of ETA and ETB receptors. We performed a hemoglobin S (HbS) polymerization assay with three concentrations of ET-1 (1, 20, and 50 pg/mL) and bosentan (100 nmol/L). ET-1 increased HbS polymerization at all concentrations, and this effect was suppressed by bosentan. For the deformability assay, red blood cells (RBCs) were incubated on a Sephacryl column with the same concentrations of ET-1 and bosentan. ET-1 decreased deformability, and this effect was reversed by bosentan. To observe erythrocyte adhesion, ET-1 and bosentan were incubated with RBCs in thrombospondin-coated 96-well plate, which demonstrated that ET-1 decreased adhesion but that bosentan enhanced adhesion. We also assessed erythrocyte apoptosis and observed decreased eryptosis induced by ET-1, and these effects were inhibited bosentan. Thus, these findings demonstrated that ET-1 modulates HbS polymerization, erythrocyte deformability, adhesion to thrombospondin, and eryptosis, and these effects were suppressed or enhanced by bosentan.

Crystal structure of Pisum arvense seed lectin (PAL) and characterization of its interaction with carbohydrates by molecular docking and dynamics.

The Pisum arvense lectin (PAL), a legume protein belonging to the Vicieae tribe, is capable of specific recognition of mannose, glucose and its derivatives without altering its structure. In this work, the three-dimensional structure of PAL was determined by X-ray crystallography and studied in detail by a combination of molecular docking and molecular dynamics (MD). Crystals belonging to monoclinic space group P21 were grown by the vapor diffusion method at 293 K. The structure was solved at 2.16 Å and was similar to that of other Vicieae lectins. The structure presented Rfactor and Rfree of 17.04% and 22.08%, respectively, with all acceptable geometric parameters. Molecular docking was performed to analyze interactions of the lectin with monosaccharides, disaccharides and high-mannose N-glycans. PAL demonstrated different affinities on carbohydrates, depending on bond orientation and glycosidic linkage present in ligands. Furthermore, the lectin interacted with representative N-glycans in a manner consistent with the biological effects described for Vicieae lectins. Carbohydrate-recognition domain (CRD) in-depth analysis was performed by MD, describing the behavior of CRD residues in complex with ligand, stability, flexibility of the protein over time, CRD volume and topology. This is a first report of its kind for a lectin of the Vicieae tribe.

Purification of a thermostable antinociceptive lectin isolated from Andira anthelmia.

Andira anthelmia (tribe Dalbergieae), a plant from Brazilian Amazon, possesses a seed lectin that was purified by affinity chromatography in sepharose-mannose. This novel Dalbergieae lectin, named AAL, agglutinated rabbit erythrocytes treated with trypsin. The hemagglutinating activity of AAL was maintained after incubation at a wide range of temperature (40 to 70 °C) and pH, was shown to be dependent on divalent cations, and was inhibited by d-mannose and d-sucrose. AAL showed an electrophoretic profile in sodium dodecyl sulfate-polyacrylamide gel electrophoresis similar to other lectins of the tribe Dalbergieae, presenting a double band of molecular weight with approximately 20 kDa and other minor bands of 17, 15, and 13 kDa, being the smaller fragment glycosylated. AAL injected by intravenous route in mice showed antinociceptive activity in two behavioral tests (writhing and formalin). In the writhing test induced by acetic acid, AAL showed inhibitory effect at 0.01 mg/kg (68%), 0.1 mg/kg (46%) and 1 mg/kg (74%). In the formalin test, AAL (0.1 mg/kg) inhibited by 48% the licking time in the inflammatory phase, an effect that was recovered by the lectin association with mannose. In conclusion, AAL presents analgesic effect involving the lectin domain via peripheral mechanisms of inflammatory nociception. This activity highlights the importance of lectins as tools to be used for understanding the interaction of protein-carbohydrate in processes associated to inflammatory pain. Copyright © 2015 John Wiley & Sons, Ltd.

TSH Receptor Reduces Hemoglobin S Polymerization and Increases Deformability and Adhesion of Sickle Erythrocytes.

SCD is a hereditary disorder caused by genetic mutation in the beta-globin gene, resulting in abnormal hemoglobin, HbS that forms sickle-shaped erythrocytes under hypoxia. Patients with SCD have endocrine disorders and it was described that 7% of these patients have clinical hypothyroidism. Recent studies have shown that mature erythrocytes possess TSH receptors. Thus, we aimed to assess the effects of TSH on SCD erythrocytes. The experiments were conducted using different concentrations of TSH (1, 2, 3, and 5 mIU/L). In HbS polymerization assay, erythrocytes were exposed to TSH in hypoxia to induce polymerization, and measurements were taken for 30 minutes. The deformability assay was made using Sephacryl-S 500 columns to separate deformable from nondeformable cells. Static adhesion test utilized thrombospondin to assess erythrocyte adhesion in the presence of TSH. TSH at all contractions were able to reduce polymerization of HbS and increase deformability. The static adhesion of erythrocytes at the lowest concentrations of 1 and 2 mIU/L were increased, but at higher contractions of 3 and 5 mIU/L, static adhesion was not modulated. The results suggest that TSH has potential involvement in the pathophysiology of sickle cell disease by inhibiting HbS polymerization, positively modulating deformability and impacting static adhesion to thrombospondin.

Unraveling DEHP influence on hemoglobin S polymerization in sickle cell disease: Ex vivo, in vitro and in silico analysis.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy, caused by a mutation at position 6 of the ß-globin chain and patients are frequently exposed to several blood transfusions in order to maintain physiological function. Transfusion blood bags are composed of PVC and phthalates (as DEHP) are often introduced to the material in order to confer malleability. In this sense, DEHP can easily elute to the blood and cause harmful effects. This study aimed to unravel DEHP effect on SCD patient's hemoglobin function. We found that HbS polymerization using whole erythrocytes is decreased by DEHP in ex vivo experiments and this effect might be mediated by the DEHP-VAL6 interaction, evaluated in silico. Isolated HbS exhibited less polymerization at low DEHP concentrations and increased polymerization rate at higher concentration. When analyzing the propensity to aggregate, HbS is more inclined to aggregate when compared to HbA due to the residue 6 mutation. Circular dichroism showed characteristic hemoglobin peaks for oxygenated HbS that are lost when oxygen is sequestered, and DEHP at higher concentration mildly recovers a peak close to the second hemoglobin one. Finally, by transmission electron microscopy we demonstrated that high DEHP concentration increased polymer formation with a more organized structure. These findings show for the first-time the beneficial effect of low-dose DEHP on HbS polymerization.

ATR1 Angiotensin II Receptor Reduces Hemoglobin S Polymerization, Phosphatidylserine Exposure, and Increases Deformability of Sickle Cell Disease Erythrocytes.

Angiotensin II (Ang II) regulates blood volume and stimulates erythropoiesis through AT1 (ATR1) and AT2 (ATR2) receptors, found in multiple tissues, including erythrocytes. Sickle cell disease (SCD) patients present altered Ang II levels. Hemoglobin S polymerization, deformability and phosphatidylserine translocation are important features of mature erythrocytes, therefore, our hypothesis is Ang II affects these parameters and, if it does, what would be the influence of AT1R and AT2R on these effects. A polymerization assay (PA), deformability, and annexin V binding were performed in SCD erythrocytes samples adding Ang II, ATR1 antagonist (losartan or eprosartan), and ATR2 antagonist (PD123319). Through the PA test, we observed a dose-dependent polymerization inhibition effect when comparing Ang II to control. Losartan did not affect the level or the rate of Ang II inhibition, while PD123319 showed an increased level of protection against polymerization, and eprosartan brought levels back to control. Ang II was able to reduce the translocation of phosphatidylserine from the inner to the outer leaflet, a marker of eryptosis, in the presence of PD123319. Also, ATR1 showed a positive effect increasing deformability. Our data shows that ATR1 is important for maintenance of erythrocyte physiological function in SCD and for prolonging its life.

Signaling Pathway in the Osmotic Resistance Induced by Angiotensin II AT2 Receptor Activation in Human Erythrocytes.

BACKGROUND: Angiotensin II regulates blood volume via AT1 (AT1R) and AT2 (AT2R) receptors. As cell integrity is an important feature of mature erythrocyte, we sought to evaluate, in vitro, whether angiotensin II modulates resistance to hemolysis and the signaling pathway involved. METHODS: Human blood samples were collected and hemolysis assay and angiotensin II signaling pathway profiling in erythrocytes were done. RESULTS: Hemolysis assay created a hemolysis curve in presence of Ang II in several concentrations (10-6 M, 10-8 M, 10-10 M, 10-12 M). Angiotensin II demonstrated protective effect, both in osmotic stressed and physiological situations, by reducing hemolysis in NaCl 0.4% and 0.9%. By adding receptors antagonists (losartan, AT1R antagonist and PD 123319, AT2R antagonist) and/or signaling modulators for AMPK, Akt/PI3K, p38 and PKC we showed the protective effect was enhanced with losartan and abolished with PD 123319. Also, we showed activation of p38 as well as PI3K/Akt pathways in this system. CONCLUSION: Ang II protects human erythrocytes from hypo-osmotic conditions-induced hemolysis by activating AT2 receptors and triggering intracellular pathways.

Impact Of Sars-Cov-2 And Its Reverberation In Global Higher Education And Mental Health.

BACKGROUND: According to UNESCO's monitoring, more than 160 countries implemented nationwide closures, which impacted over 87% of the world's student population. Several other countries implemented localized school closures; should these closures become nationwide, millions of additional learners will experience education disruption. Universities from around the world have been uncertain about how long the coronavirus crisis will last and how it might affect the mental health of students and faculty. The psychological impact has been a critical disruptor, creating anxiety and uncertainty. METHOD: The data were cross-checked with information from the main international newspapers. RESULTS: By discussing online and distance education, the coronavirus opens an important and urgent issue that affects mental health - these are virtually unexplored topics, and their results have not been validated yet. Online education is not limited to distance education, as it regards a grouping of learning/teaching procedures completed in cyberspace. Blended learning was, thus, introduced as a tool in personalized learning to adjust to new realities. These are unprecedented circumstances, and we understand they create stress, favoring anguish and a fierce search for new knowledge acquisition. CONCLUSIONS: Current research highlights that anxiety and depression, exacerbated by uncertainties and intensification of the information flow, will grow extensively. Negative physiological consequences of stress will manifest. For instance, loneliness, which will increase under these circumstances, seems to have a negative impact on education and, therefore, on psychological pain and suffering.

When health professionals look death in the eye: the mental health of professionals who deal daily with the 2019 coronavirus outbreak.

BACKGROUND: The fact that COVID-19 is transmissible from human to human and associated with high morbidity and potentially fatality can intensify the perception of personal danger. In addition, the foreseeable shortage of supplies and an increasing flow of suspected and real cases of COVID-19 contribute to the pressures and concerns of health professionals. METHOD: The studies were identified in well-known international journals found in two electronic databases: Scopus and Embase. The data were cross-checked with information from the main international newspapers. RESULTS: Work-related stress is a potential cause of concern for health professionals. It has been associated with anxiety including multiple clinical activities, depression in the face of the coexistence of countless deaths, long work shifts with the most diverse unknowns and demands in the treatment with patients with COVID-19. Therefore, it is an important indicator of psychic exhaustion. CONCLUSIONS: As coronavirus cases increase and deaths surge in Italy, new figures show an "enormous" level of contagion among the country's medical personnel. At least 2,629 health workers have been infected with coronavirus since the outbreak onset in February, representing 8.3% of total cases. The percentage of infected health workers has almost doubled the number registered in China throughout the epidemic. Intensive care unit physicians are on their stress limit, especially when dealing with older patients and with death prospects. Doctors, not a relative, are inevitably the last people a dying COVID-19 patient will see.

Genotyping of Single Nucleotide Polymorphisms Using Allele-Specific qPCR Producing Amplicons of Small Sizes Directly from Crude Serum Isolated from Capillary Blood by a Hand-Powered Paper Centrifuge.

The cell-free genomic DNA (gDNA) concentration in serum ranges from 1500 to 7500 copies/mL within 2 h after phlebotomy (6⁻24 times the concentration observed in plasma). Here, we aimed to evaluate the gDNA size distribution in serum with time after coagulation and to test if crude serum can be directly used as a source of gDNA for qPCR. Next, we investigated if single nucleotide polymorphisms (SNPs) could be genotyped directly from the crude serum isolated from capillary blood using a hand-powered paper centrifuge. All tested PCR targets (65, 100, 202 and 688 base pairs) could be successfully amplified from DNA extracted from serum, irrespective of their amplicon size. The observed qPCR quantitation cycles suggested that the genomic DNA yield increased in serum with incubation at room temperature. Additionally, only 65 and 101 base pair qPCR targets could be amplified from crude serum soon after the coagulation. Incubation for 4 days at room temperature was necessary for the amplification of PCR targets of 202 base pairs. The 688 base pair qPCR target could not be amplified from serum directly. Lastly, serum was successfully separated from capillary blood using the proposed paper centrifuge and the genotypes were assigned by testing the crude serum using allele-specific qPCR, producing small amplicon sizes in complete agreement with the genotypes assigned by testing the DNA extracted from whole blood. The serum can be used directly as the template in qPCR for SNP genotyping, especially if small amplicon sizes are applied. This shortcut in the SNP genotyping process could further molecular point-of-care diagnostics due to elimination of the DNA extraction step.

Antibiotic Activity Potentiation and Physicochemical Characterization of the Fixed Orbignya speciosa Almond Oil against MDR Staphylococcus aureus and Other Bacteria.

Orbignya speciosa (babassu) is an important palm tree in Brazil whose fixed almond oil is used in popular medicine and especially in food, in addition to being a research target for the manufacture of biofuels. The aim of this study was to evaluate the fixed almond oil physicochemical characterization and its antibacterial activity in isolation and in association with aminoglycosides against standard and multidrug-resistant bacteria. Analyses such as water content, pH, acidity, peroxide index, relative density, and refractive index indicate the stability and chemical quality of the oil. In the oil's GC/MS chemical composition analysis, a high saturated fatty acid (76.90%) content was observed. Lauric acid (56.28%) and oleic acid (23.10%) were the major oil components. In the antibacterial test, a more significant oil activity was observed against K. pneumoniae KP-ATCC 10031 (minimal inhibitory concentration (MIC) = 406.37 µg/mL) and Staphylococcus aureus ATCC 6538 (MIC = 812.75 µg/mL), but for the other strains-including standard and multi-resistant strains-the oil presented an MIC ≥ 1024 µg/mL. Furthermore, a synergistic effect was observed when the oil was associated with amikacin and gentamicin against S. aureus (SA-10) and an antagonistic effect was observed with amikacin against Escherichia coli. Data indicate the O. speciosa oil as a valuable nutritional source of lauric, oleic, and myristic fatty acids with an ability to modulate aminoglycoside activity.

Flow Cytometric Analysis of Erythrocytes Osmotic Fragility in Hereditary Spherocytosis: A Case-Controlled Study Evaluating the Best Anticoagulant, Sample Pre-Treatment and NaCl Concentration for Reliable Screening of this Red Blood Cell Membrane Disorder.

BACKGROUND: The cytometric flow osmotic fragility test (FC-OFT) was recently introduced. However, the test is still under development and some variables have not yet been fully tested. METHODS: The osmotic fragility of hereditary spherocytosis (HS) cases and healthy controls were evaluated by FC-OFT using a series of tubes containing decreasing concentrations of NaCl. The analyses were executed in fresh and incubated (37°C for 24 h) blood samples anticoagulated with EDTA and heparin. The percentages of residual red blood cells were used to plot the osmotic fragility curves. The OF curves of each tested condition were compared using the median corpuscular fragility (MCF). ROC curve analyses identified the most accurate NaCl concentrations for differentiation between HS cases and healthy controls. RESULTS: FC-OFT curves assumed a sigmoidal dose-response shape and the MCF of cases and controls were different in all instances. MCF comparisons revealed that incubation and anticoagulant have major and minor effects on the FC-OFT, respectively. One hundred percent of sensitivity and specificity was obtained from 5.5 to 6.0 g/L of NaCl in EDTA-treated fresh blood, from 6.0 to 8.0 g/L of NaCl in EDTA-treated incubated blood, and in none of the tested NaCl concentration in heparinized blood. CONCLUSIONS: EDTA is the anticoagulant of choice for the assay. Incubation at 37°C for 24 h increased its diagnostic capability. The most reliable NaCl concentration for the discrimination of HS case from controls was 6.0 g/L of NaCL in fresh EDTA-treated blood, and was 7.5 g/L of NaCl in incubated EDTA-treated blood. © 2018 International Clinical Cytometry Society.

Antioxidative effect and phytochemical profile of natural products from the fruits of "babaçu" (Orbignia speciose) and "buriti" (Mauritia flexuosa).

Orbignya speciosa and Mauritia flexuosa are two native palm tree species found in Brazil. Their fruits are rich in edible fixed oils, which are used for many purposes in industry, such as in the manufacture of soaps, surfactants and margarines. The aim of this work was to characterize the chemical profiles and antioxidant properties of the methanol extracts obtained from the fruits of O. speciosa and M. flexuosa. The chemical prospection was carried out using specific qualitative tests to evaluate the presence of phenolic compounds (tannins and flavonoids) in the extracts of both species. The antioxidant properties of the extracts were analyzed by the following methods: production of thiobarbituric acid reactive substances (TBARS) from phospholipids, deoxyribose degradation, radical-scavenging activity-DPPH, iron chelation assay and ferric-reducing antioxidant power (FRAP). The methanolic extracts obtained from M. flexuosa and O. speciosa presented significant antioxidant activities, although M. flexuosa presented higher antioxidant activity than O. speciosa. In conclusion, M. flexuosa and O. speciosa are important sources of antioxidant substances that may be useful in the development of new products to prevent diseases associated with oxidative stress.

Production of native arbuscular mycorrhizal fungi inoculum under different environmental conditions.

In order to obtain an arbuscular mycorrhizal fungi (AMF) native inoculum from Sierra de Moa and determine the most appropriate conditions for its big scale production, four light and temperature combinations were tested in three plant species (Calophyllum antillanum, Talipariti elatum and Paspalum notatum). Growth and development parameters, as well as the mycorrhizal functioning of the seedlings were evaluated. The natural light treatment under high temperatures (L-H) was the most suitable for the growth and development of the three plant species, showing the highest total biomass values, mainly of root, and a positive root-shoot ratio balance. This treatment also promoted higher values of root mycorrhizal colonization, external mycelium and AMF spore density. A total of 38 AMF species were identified among the plants and environmental conditions tested. Archaeospora sp.1, Glomus sp.5, Glomus brohultii and G. glomerulatum were observed in all the treatments. The L-H condition can be recommended for native inoculum production, as it promotes a better expression of the AM symbiosis and an elevated production of mycorrhizal propagules.

Full-mouth ultrasonic debridement in the treatment of patients with diabetes and severe chronic periodontitis: preliminary study / Debridamento ultrassônico de boca toda no tratamento da periodontite crônica severa em pacientes diabéticos: estudo preliminar

ABSTRACT Objective: The purpose of this study was to clinically evaluate the effect of one-stage full-mouth ultrasonic debridement in the treatment of diabetic subjects with severe chronic periodontitis. Methods: Sixteen patients with uncontrolled diabetes (glycated hemoglobin ≥ 7%) and severe chronic periodontitis (at least 8 teeth with a probing depth and bleeding on probing were selected and randomly assigned to 2 treatment groups: control group (n=7) - quadrant-wise scaling and root planning; test group (n=9) - full-mouth ultrasonic debridement in one session of 45 minutes. The following outcomes were assessed: plaque index, gingival index, bleeding on probing, probing depth, clinical attachment level and gingival margin position. All parameters were assessed at baseline, 1 and 3 months after treatment. Probing depth, clinical attachment level and gingival margin position were analyzed using ANOVA and Tukey test, and the other clinical parameters analysed with the Friedman and Mann-Whitney tests. Results: An improvement in probing depth, clinical attachment level was observed after treatment in both groups, but without statistically significant differences between them. After 3 months, in initially deep pockets, the PD decreased 1.6 mm and 1.7 mm in test and control group, respectively. Clinical attachment level gain ≥ 2 mm was statistically significant at sites in control (10.1%) and test (13,4%) groups in 3 months. Conclusions: One-stage full-mouth ultrasonic debridement promoted similar clinical outcomes to those obtained with the scaling and root planning in the treatment of diabetic subjects with severe chronic periodontitis.

RESUMO Objetivo: Avaliar clinicamente o efeito do debridamento ultrassônico de boca toda no tratamento da periodontite crônica severa em pacientes diabéticos. Métodos: Dezesseis pacientes diabéticos descompensados (Hemoglobina Glicada ≥ 7%) com periodontite crônica severa (mínimo de 8 dentes com profundidade de sondagem ≥ 5 mm e sangramento à sondagem) separados aleatoriamente em 2 grupos: Controle (7): raspagem e alisamento radicular por quadrante e Teste (9): debridamento ultrassônico sessão única de 45 minutos. Os parâmetros clínicos avaliados foram: Índice de placa, Índice gengival, Sangramento à Sondagem, Profundidade de Sondagem, Nível de inserção clínico e Posição da Margem Gengival. As variáveis foram avaliadas no início, 1 e 3 meses após o tratamento. Para análise das variáveis quantitativas (Profundidade de sondagem, Nível de inserção e Posição da margem gengival de bolsas moderadas) foram realizados ANOVA e teste de Tukey e para as demais foram utilizados os testes de Friedman e Mann-Whitney. Resultados: Observou-se melhora na profundidade de sondagem e nível de inserção clínica após o tratamento em ambos os grupos, sem diferenças estatisticamente significativas entre eles. Após 3 meses, nas bolsas inicialmente profundas, a profundidade de sondagem reduziu 1,6 e 1,7 mm nos grupos teste e controle, respectivamente. Houve um ganho estatisticamente significante no nível de inserção ≥ 2 mm nos grupos controle (10,1%) e teste (13,4%), aos 3 meses. Conclusão: O debridamento ultrassônico de boca toda promoveu resultados clínicos semelhantes aos obtidos com a raspagem e alisamento radicular no tratamento da periodontite crônica severa em indivíduos diabéticos.

Itinerário da família para obter o diagnóstico da criança com necessidades especiais de saúde / Itinerario de la familia para obtener el diagnóstico del niño con necesidades especiales de salud / The itinerary of families to obtain the diagnosis of the children with special healthcare needs

RESUMO Objetivo: conhecer o itinerário percorrido pela família para a obtenção do diagnóstico da criança com necessidades especiais de saúde. Método: realizou-se estudo qualitativo em uma unidade de internação pediátrica do sul do Brasil. Utilizou-se como referencial metodológico a Grounded Theory. Participaram 16 familiares cuidadores. Os dados foram coletados em 2019 por entrevistas e submetidos à codificação aberta e axial. Resultados: as famílias percorreram um longo itinerário até o recebimento do diagnóstico da criança: detectaram alterações no seu estado geral, realizaram diversos exames, desconfiaram o diagnóstico por já ter outros com o mesmo na família, receberam informações dos profissionais da saúde acerca dos cuidados necessários e dos serviços especializados para o seu tratamento, apresentaram medo, pânico, negação e valorizaram a fé em Deus na esperança da melhora da criança. Considerações finais: o enfermeiro necessita desenvolver um processo educativo junto à família para que ela se sinta preparada e capaz de cuidar dessas crianças.

RESUMEN Objetivo: conocer el itinerario recorrido por la familia para la obtención del diagnóstico del niño con necesidades especiales de salud. Método: se realizó estudio cualitativo en una unidad de hospitalización pediátrica del sur de Brasil. Se utilizó como referencial metodológico la GroundedTheory. Participaron 16 familiares cuidadores. Los datos fueron recolectados en 2019 por entrevistas y sometidos a la codificación abierta y axial. Resultados: las familias recorrieron un largo itinerario hasta la recepción del diagnóstico del niño: detectaron alteraciones en su estado general; realizaron diversos exámenes; desconfiaron del diagnóstico por tener ya otros con el mismo en la familia; recibieron informaciones de los profesionales de la salud acerca de los cuidados necesarios y de los servicios especializados para su tratamiento; presentaron miedo, pánico y negación; y valoraron la fe en Dios en la esperanza de la mejora del niño. Consideraciones finales: el enfermero necesita desarrollar un proceso educativo con la familia para que ella se sienta preparada y capaz de cuidar a esos niños.

ABSTRACT Objective: to know the itinerary taken by the family to obtain the diagnosis of the children with special health needs. Method: a qualitative study was carried out in a pediatric inpatient unit in southern Brazil. Grounded Theory was used as a methodological reference. Sixteen (16) family caregivers participated. Data were collected in 2019 through interviews and submitted to open and axial coding. Results: the families traveled a long route until receiving the children's diagnosis: they detected changes in their general condition; performed several exams; they were suspicious of the diagnosis because other members of the family had already been diagnosed with the same conditions; received information from health professionals about the necessary care and specialized services for the treatment; showed fear, panic and denial; and they valued faith in God in the hope of improving of the children. Final considerations: nurses need to develop an educational process with the family so that they feel prepared and capable of taking care of these children.

Macrophage Migration Inhibitory Factor (MIF): Biological Activities and Relation with Cancer.

Macrophage migration inhibitory factor (MIF) emerged in recent years as an important inflammation mediator, playing a prominent role in the pathogenesis of various types of malignant neoplasm. MIF is a glycoprotein that presents a wide spectrum of biological activities and exerts a complex interaction with various cellular signaling pathways, causing imbalance of homeostasis. Experimental and clinical studies show that high levels of MIF are found in almost all types of human cancers and are implicated in seemingly all stages of development of the tumors. The production of MIF is triggered through an autocrine signal emitted by tumor cells, and stimulates the production of cytokines, chemokines, and growth as well as angiogenic factors that lead to growth of the tumor, increasing its aggressiveness and metastatic potential. MIF is produced by virtually all types of human body cells, in response to stress caused by different factors, leading to pathological conditions such as chronic inflammation and immunomodulation with suppression of immune surveillance and of immune response against tumors, angiogenesis, and carcinogenesis. In this review, we present recent advances on the biological activity of MIF, the signaling pathways with which it is involved and their role in tumorigenesis.

Dificuldades encontradas pela família no cuidado à criança/adolescente com HIV / Difficulties encountered by families in caring for children or adolescents with HIV / Dificultades encontradas por la familia en el cuidado al niño/adolescente con VIH

Objetivo: conhecer as dificuldades encontradas pela família para o cuidado à criança/adolescente com HIV. Metodologia: pesquisa qualitativa realizada em um Hospital Dia no sul do Brasil em 2018. Participaram 20 familiares cuidadores de crianças/adolescentes soropositivas. Os dados foram coletados por entrevistas e submetidos à Análise de Conteúdo. Respeitaram-se os princípios éticos. Resultados: as famílias afirmaram não ter facilidades no cuidado. Referiram dificuldades em manter o sigilo do diagnóstico para a criança/adolescente; na adesão desta à medicação e minimização dos seus efeitos colaterais, em seguir os horários de administração; na assiduidade às consultas; em sofrer preconceito e na aceitação da sociedade diante da doença, incluindo a preocupação com o futuro da criança/adolescente. Conclusão: verificou-se como importante a atuação dos profissionais da saúde/ enfermeiros investindo em uma assistência voltada para a promoção de saúde de crianças e adolescentes com HIV, promovendo educação em saúde e o manejo das dificuldades enfrentadas com o cuidado.

Objective: to learn the difficulties encountered by families in caring for children or adolescents with HIV. Methodology: this qualitative study was conducted at a day hospital in southern Brazil in 2018. The participants were 20 family caregivers of seropositive children or adolescents. Data were collected through interviews and subjected to Content Analysis. Ethical principles were respected. Results: the families claimed to have no care facilities. They reported difficulties in keeping the children's or adolescents' diagnosis confidential; securing adherence to medication and administration schedules; minimizing side effects; attending appointments; suffering prejudice and gaining social acceptance of the disease, which included concern for the children's or adolescents' futures. Conclusion: it was found to be important that health professionals' or nurses' invest in care focused on promoting the health of children and adolescents with HIV, furthering health education and managing the difficulties encountered in care.

Objetivo: conocer las dificultades encontradas por la familia para el cuidado al niño/adolescente con VIH. Método: investigación cualitativa realizada en un Hospital Día en el sur de Brasil en 2018. Participaron 20 familiares cuidadores de niños/adolescentes seropositivos. Los datos fueron recolectados por entrevistas y sometidos al Análisis de Contenido. Se respetaron los principios éticos. Resultados: las familias afirmaron no tener facilidades en el cuidado. Dijeron que tienen dificultades para mantener el secreto del diagnóstico junto al niño/adolescente, también para su adherencia a la medicación y minimización de sus efectos colaterales, para seguir los horarios correctos de administración; la asiduidad de las consultas; por sufrir con los prejuicios y la dificultad de aceptación social de la enfermedad y la preocupación por el futuro del niño/adolescente. Conclusión: se verificó que es muy importante la actuación de los profesionales de salud/enfermeros que invierten en una atención volcada a la promoción de salud de niños y adolescentes con VIH, promoviendo la educación sanitaria y la gestión de las dificultades enfrentadas con el cuidado.

Rede de apoio social da família para o cuidado da criança com paralisia cerebral / Social support network of the family for the care of children with cerebral palsy / Red de apoyo social de la familia para el cuidado del niño con parálisis cerebral

Objetivo: analisar a rede de apoio social utilizada pela família para cuidar a criança com paralisia cerebral. Método: pesquisa qualitativa, descritiva, realizada com 12 mães de crianças com paralisia cerebral atendidas em unidade de pediatria do Hospital Universitário de Rio Grande. Os dados foram coletados nos meses de agosto e setembro de 2018, por meio de entrevista semiestruturada, e submetidos à análise temática. Resultados: identificou-se a rede de apoio social formada pelos familiares, amigos, vizinhos, profissionais de saúde e ancorada pela fé em Deus. As mães foram protagonistas do cuidado e algumas não receberam nenhum tipo de apoio para os cuidados dos filhos. Conclusão: a rede de apoio social contribuiu para a superação de dificuldades da família e para o cuidado da criança, sendo fonte de apoio emocional, financeiro, ajuda com o transporte, remédios e orientação dos profissionais de saúde/enfermagem.

Objective: to know the social support network used by the family to care for children with cerebral palsy. Method: this qualitative and descriptive research was conducted with twelve mothers of children with cerebral palsy assisted at a pediatric unit of a University Hospital in Rio Grande. Data were collected in August and September 2018 through semi-structured interviews and submitted to thematic analysis. Results: we identified the social support network consisting of family, friends, neighbors, health professionals, and faith in God. Mothers were protagonists of care and some received no support for childcare. Conclusion: the social support network contributed to overcome family difficulties and childcare, being a source of emotional, financial support, help with transportation, medicine, and guidance from health/nursing professionals.

Objetivo: conocer la red de apoyo social utilizada por la familia para cuidar a niños con parálisis cerebral. Método: investigación cualitativa, descriptiva, realizada con doce madres de niños con parálisis cerebral atendidas en una unidad de pediatría de un Hospital Universitario de Río Grande. Los datos se recopilaron en agosto y septiembre de 2018 a través de entrevistas semiestructuradas y se sometieron a análisis temáticos. Resultados: identificamos que la red de apoyo social estaba formada por familiares, amigos, vecinos, profesionales de la salud y fe en Dios. Las madres fueron protagonistas de la atención y algunas no recibieron apoyo para el cuidado de los niños. Conclusión: la red de apoyo social contribuyó a superar las dificultades familiares y el cuidado de los niños, siendo una fuente de apoyo emocional y financiero, ayuda con el transporte, medicamentos y orientación de profesionales de la salud/enfermeros.