Quality of life of adolescents with type 1 diabetes

INTRODUCTION: Diabetes mellitus is a highly prevalent chronic disease. Type 1 diabetes mellitus usually develops during infancy and adolescence and may affect the quality of life of adolescents. OBJECTIVE: To evaluate the quality of life of adolescents with type 1 diabetes mellitus in a metropolitan region of western central Brazil. METHODS: Adolescents aged 10-19 years who had been diagnosed with type 1 diabetes mellitus at least 1 year previously were included. Patients with verbal communication difficulties, severe disease, and symptomatic hypo- or hyperglycemic crisis as well as those without an adult companion and who were ;7%. In general, the adolescents consistently reported having a good quality of life. The median scores for the domains of the instrument were as follows: “satisfaction”: 35; “impact”: 51; and “worries“: 26. The total score for all domains was 112. Bivariate analysis showed significant associations among a lower family income, public health assistance, and insulin type in the “satisfaction” domain; and a lower family income, public health assistance, public school attendance, and a low parental education level in the “worries“ domain and for the total score. A longer time since diagnosis was associated with a lower total score. Multivariable analysis confirmed the association of a worse quality of life with public health assistance, time since diagnosis, and sedentary lifestyle in the “satisfaction” domain; female gender in the “worries” domain; and public health assistance for the total score. CONCLUSIONS: Overall, the adolescents evaluated in this study viewed their quality of life as good. Specific factors that led to the deterioration of quality of life, including public assistance, time since diagnosis, sedentary lifestyle, and female gender, were identified. No potential conflict of interest was reported

A different type of acute myocarditis : A case report of acute autoimmune myocarditis mediated by anti-PD-1 T lymphocyte receptor (pembrolizumab)

Pembrolizumab is an immune check-point inhibitor (ICI), which acts by blocking the T lymphocyte PD-1 inhibitor receptor. It has been increasingly used in advanced or non-responsive tumours with promising results. However, acute myocarditis is an infrequent but potentially life-threatening autoimmune adverse effect related to ICIs. This case deals with a 69-year-old gentleman on second-line therapy with pembrolizumab for advanced non-small cell lung cancer. Three weeks after first dose, the patient was diagnosed with an autoimmune hepatitis, treated with decreasing corticoid dosage, followed by acute heart failure. On admission, his electrocardiogram (ECG) showed diffuse repolarization changes and a transthoracic echocardiography revealed severe left ventricle impairment (left ventricular ejection fraction 32%). High-sensitivity cardiac troponin was elevated and a coronary angiogram was performed showing non-significant obstructive disease. An autoimmune myocarditis was suspected, and high-dose intravenous corticoid, intravenous vasodilators, and loop diuretics were started with favourable response. Cardiac magnetic resonance (CMR) imaging, performed 2 weeks after clinical onset, revealed extracellular oedema in the anteroseptal-apical left ventricle segments. A new transthoracic echocardiography, performed after 3 months, showed preserved left ventricle ejection fraction. Finally, the patient was readmitted due to an autoimmune myasthenia-like syndrome. Acute autoimmune myocarditis related to ICIs is a challenging diagnosis and its incidence has been underestimated in early studies. Endomyocardial biopsy (EMB) is the gold standard test for its diagnosis. Nevertheless, a definite myocarditis diagnosis is possible without EMB when characteristic clinical syndrome, elevated myonecrosis markers, and electrocardiographic, echocardiographic, and CMR changes are present together

Inframalleolar Bypass Grafts for Limb Salvage

AbstractObjectiveTo report our experience of long-term results of inframalleolar bypass.DesignRetrospective analysis.Materials and methodsWe analysed 122 inframalleolar bypasses performed between January 1991 and June 2005 in 116 patients. Most patients were treated for critical ischaemia (97%). The indication for the use of podalic arteries was a lack of tibial arteries with run-off to the foot. The dorsalis pedis was predominantly used for distal anastomoses (62.3%) and the greater saphenous vein (84.4%) as the conduit. The follow-up periods ranged from 1 to 60 months. The endpoints analysed were graft patency, limb salvage, preservation of deambulation and survival rate.ResultsThe cumulative patency was 58.2% at 3 years and 53.4% at 5 years. The best results were achieved with the devalvulated greater saphenous veins. Limb salvage was 70.0% at 3 years and 50.4% at 5 years, with preserved deambulation rates of 57.3% and 47.1%, respectively. There were 36 major and 45 minor amputations. At 3 years, the survival rate was 50.2% and the surgical mortality 13%. Female sex was associated with worse results for cumulative patency and limb salvage (P<0.01).ConclusionsIn the long term, inframalleolar bypass is a satisfactory option for limb salvage

Cell membrane and bioactive factors derived from mesenchymal stromal cells: Cell-free based therapy for inflammatory bowel diseases

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract associated with multifactorial conditions such as ulcerative colitis and Crohn's disease. Although the underlying mechanisms of IBD remain unclear, growing evidence has shown that dysregulated immune system reactions in genetically susceptible individuals contribute to mucosal inflammation. However, conventional treatments have been effective in inducing remission of IBD but not in preventing the relapse of them. In this way, mesenchymal stromal cells (MSC) therapy has been recognized as a promising treatment for IBD due to their immunomodulatory properties, ability to differentiate into several tissues, and homing to inflammatory sites. Even so, literature is conflicted regarding the location and persistence of MSC in the body after transplantation. For this reason, recent studies have focused on the paracrine effect of the biofactors secreted by MSC, especially in relation to the immunomodulatory potential of soluble factors (cytokines, chemokines, and growth factors) and extracellular vehicles that are involved in cell communication and in the transfer of cellular material, such as proteins, lipids, and nucleic acids. Moreover, treatment with interferon-γ, tumor necrosis factor-α, and interleukin- 1β causes MSC to express immunomodulatory molecules that mediate the suppression via cell-contact dependent mechanisms. Taken together, we present an overview of the role of bioactive factors and cell membrane proteins derived from MSC as a cell-free therapy that can improve IBD treatment

Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

As hypoxia-induced inflammatory angiogenesis may contribute to sickle cell disease manifestations, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from steady-state sickle cell anemia patients presented elevated concentrations of pro-angiogenic factors (Angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly augmenting endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice, compared with non-sickle cell disease mice, consistent with an upregulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy displayed a pro-angiogenic profile and had more significant effects on endothelial cell proliferation and capillary formation than plasma of patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factor profile, in association with an inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, sickle cell anemia and retinopathic hemoglobin SC individuals present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy for preventing progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.As hypoxia-induced inflammatory angiogenesis may contribute to sickle cell disease manifestations, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated an1006730739FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNPQ - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO2008/57441-0; 2009/16334-0565036/201

The electron-furfural scattering dynamics for 63 energetically open electronic states

14 págs.; 15 figs.We report on integral-, momentum transfer- and differential cross sections for elastic and electronically inelastic electron collisions with furfural (CHO). The calculations were performed with two different theoretical methodologies, the Schwinger multichannel method with pseudopotentials (SMCPP) and the independent atom method with screening corrected additivity rule (IAM-SCAR) that now incorporates a further interference (I) term. The SMCPP with N energetically open electronic states (N) at either the static-exchange (N ch-SE) or the static-exchange-plus-polarisation (N ch-SEP) approximation was employed to calculate the scattering amplitudes at impact energies lying between 5 eV and 50 eV, using a channel coupling scheme that ranges from the 1ch-SEP up to the 63ch-SE level of approximation depending on the energy considered. For elastic scattering, we found very good overall agreement at higher energies among our SMCPP cross sections, our IAM-SCAR+I cross sections and the experimental data for furan (a molecule that differs from furfural only by the substitution of a hydrogen atom in furan with an aldehyde functional group). This is a good indication that our elastic cross sections are converged with respect to the multichannel coupling effect for most of the investigated intermediate energies. However, although the present application represents the most sophisticated calculation performed with the SMCPP method thus far, the inelastic cross sections, even for the low lying energy states, are still not completely converged for intermediate and higher energies. We discuss possible reasons leading to this discrepancy and point out what further steps need to be undertaken in order to improve the agreement between the calculated and measured cross sections. ©2016 AIP Publishing LLCR.F.d.C., M.C.A.L., M.H.F.B., M.T.d.N.V., and M.A.P.L. acknowledge support from the Brazilian agency Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). M.T.d.N.V. acknowledges support from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). D.B.J. thanks the Australian Research Council (ARC) for financial support provided through a Discovery Early Career Researcher Award. M.J.B. thanks the ARC for some financial support and also thanks CNPq for his “Special Visiting Professor” award at the Federal University of Juiz de Fora. G.G. thanks the Spanish Ministerio de Economia y Competitividad under Project No. FIS2012- 31230 and the European Union COST Action No. CM1301 for funding.Peer Reviewe

Growth inhibitory effects of 3′-nitro-3-phenylamino nor-beta-lapachone against HL-60: A redox-dependent mechanism

AbstractIn this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3′-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO2) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF4) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO2. QPhNO2 caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO2 treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry

A Novel TGFβ Modulator that Uncouples R-Smad/I-Smad-Mediated Negative Feedback from R-Smad/Ligand-Driven Positive Feedback

As some of the most widely utilised intercellular signalling molecules, transforming growth factor β (TGFβ) superfamily members play critical roles in normal development and become disrupted in human disease. Establishing appropriate levels of TGFβ signalling involves positive and negative feedback, which are coupled and driven by the same signal transduction components (R-Smad transcription factor complexes), but whether and how the regulation of the two can be distinguished are unknown. Genome-wide comparison of published ChIP-seq datasets suggests that LIM dom