Cross-cultural adaptation and clinical validation of the neonatal skin condition score to Brazilian Portuguese

Objective: to describe the process of cross-cultural adaptation and clinical validation of the Neonatal Skin Condition Score. Methods: this methodological cross-cultural adaptation study included five steps: initial translation, synthesis of the initial translation, back translation, review by an Committee of Specialists and testing of the pre-final version, and an observational cross-sectional study with analysis of the psychometric properties using the Adjusted Kappa, Intraclass Correlation Coefficient, and Bland- Altman Method statistical tests. A total of 38 professionals were randomly recruited to review the clarity of the adapted instrument, and 47 newborns hospitalized in the Neonatology Unit of the Clinical Hospital of Porto Alegre were selected by convenience for the clinical validation of the instrument. Results: the adapted scale showed approximately 85% clarity. The statistical tests showed moderate to strong intra and interobserver item to item reliability and from strong to very strong in the total score, with a variation of less than 2 points among the scores assigned by the nurses to the patients. Conclusions: the scale was adapted and validated to Brazilian Portuguese. The psychometric properties of the Brazilian version of the Neonatal Skin Condition Score instrument were similar to the validation results of the original scale

Improving the flux distributions simulated with genome-scale metabolic models of Saccharomyces cerevisiae

Abstract Genome-scale metabolic models (GEMs) can be used to evaluate genotype-phenotype relationships and their application to microbial strain engineering is increasing in popularity. Some of the algorithms used to simulate the phenotypes of mutant strains require the determination of a wild-type flux distribution. However, the accuracy of this reference, when calculated with flux balance analysis, has not been studied in detail before. Here, the wild-type simulations of selected GEMs for Saccharomyces cerevisiae have been analysed and most of the models tested predicted erroneous fluxes in central pathways, especially in the pentose phosphate pathway. Since the problematic fluxes were mostly related to areas of the metabolism consuming or producing NADPH/NADH, we have manually curated all reactions including these cofactors by forcing the use of NADPH/NADP+ in anabolic reactions and NADH/NAD+ for catabolic reactions. The curated models predicted more accurate flux distributions and performed better in the simulation of mutant phenotypes.FCT -Fuel Cell Technologies Program(SFRH/BD/51111/2010

Effects of supplemented isoenergetic diets varying in cereal fiber and protein content on the bile acid metabolic signature and relation to insulin resistance

Bile acids (BA) are potent metabolic regulators influenced by diet. We studied effects of isoenergetic increases in the dietary protein and cereal-fiber contents on circulating BA and insulin resistance (IR) in overweight and obese adults. Randomized controlled nutritional intervention (18 weeks) in 72 non-diabetic participants (overweight/obese: 29/43) with at least one further metabolic risk factor. Participants were group-matched and allocated to four isoenergetic supplemented diets: control; high cereal fiber (HCF); high-protein (HP); or moderately increased cereal fiber and protein (MIX). Whole-body IR and insulin-mediated suppression of hepatic endogenous glucose production were measured using euglycaemic–hyperinsulinemic clamps with [6-62H2] glucose infusion. Circulating BA, metabolic biomarkers, and IR were measured at 0, 6, and 18 weeks. Under isoenergetic conditions, HP-intake worsened IR in obese participants after 6 weeks (M-value: 3.77 ± 0.58 vs. 3.07 ± 0.44 mg/kg/min, p = 0.038), with partial improvement back to baseline levels after 18 weeks (3.25 ± 0.45 mg/kg/min, p = 0.089). No deleterious effects of HP-intake on IR were observed in overweight participants. HCF-diet improved IR in overweight participants after 6 weeks (M-value 4.25 ± 0.35 vs. 4.81 ± 0.31 mg/kg/min, p = 0.016), but did not influence IR in obese participants. Control and MIX diets did not influence IR. HP-induced, but not HCF-induced changes in IR strongly correlated with changes of BA profiles. MIX-diet significantly increased most BA at 18 weeks in obese, but not in overweight participants. BA remained unchanged in controls. Pooled BA concentrations correlated with fasting fibroblast growth factor-19 (FGF-19) plasma levels (r = 0.37; p = 0.003). Higher milk protein intake was the only significant dietary predictor for raised total and primary BA in regression analyses (total BA, p = 0.017; primary BA, p = 0.011). Combined increased intake of dietary protein and cereal fibers markedly increased serum BA concentrations in obese, but not in overweight participants. Possible mechanisms explaining this effect may include compensatory increases of the BA pool in the insulin resistant, obese state; or defective BA transport

Different states of integrin LFA-1 aggregation are controlled through its association with tetraspanin CD9

This is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta - Mollecular Cell Research. A definitive version was subsequently published in Biochimica et Biophysica Acta - Mollecular Cell Research, 1853.10 (2015): 2464-2480 DOI: 10.1016/j.bbamcr.2015.05.018The tetraspanin CD9 has been shown to interact with different members of the β1 and β3 subfamilies of integrins, regulating through these interactions cell adhesion, migration and signaling. Based on confocal microscopy co-localization and on coimmunoprecipitation results, we report here that CD9 associates with the β2 integrin LFA-1 in different types of leukocytes including T, B and monocytic cells. This association is resistant to stringent solubilisation conditions which, together with data from chemical crosslinking, in situ Proximity Ligation Assays and pull-down experiments, suggests a primary/direct type of interaction mediated by the Large Extracellular Loop of the tetraspanin. CD9 exerts inhibitory effects on the adhesive function of LFA-1 and on LFA-1-dependent leukocyte cytotoxic activity. The mechanism responsible for this negative regulation exerted by CD9 on LFA-1 adhesion does not involve changes in the affinity state of this integrin but seems to be related to alterations in its state of aggregationThis work was supported by grant SAF2012-34561 from the Spanish «Ministerio de Economía y Competitividad-MINECO», (to C.C.). R.R.M. salary is supported by a «Profesor Ayudante» position from Departamento de Biología, Facutad de Ciencias, Universidad Autónoma de Madri

Chronic escitalopram treatment attenuated the accelerated rapid eye movement sleep transitions after selective rapid eye movement sleep deprivation: a model-based analysis using Markov chains

BackgroundShortened rapid eye movement (REM) sleep latency and increased REM sleep amount are presumed biological markers of depression. These sleep alterations are also observable in several animal models of depression as well as during the rebound sleep after selective REM sleep deprivation (RD). Furthermore, REM sleep fragmentation is typically associated with stress procedures and anxiety. The selective serotonin reuptake inhibitor (SSRI) antidepressants reduce REM sleep time and increase REM latency after acute dosing in normal condition and even during REM rebound following RD. However, their therapeutic outcome evolves only after weeks of treatment, and the effects of chronic treatment in REM-deprived animals have not been studied yet.ResultsChronic escitalopram- (10 mg/kg/day, osmotic minipump for 24 days) or vehicle-treated rats were subjected to a 3-day-long RD on day 21 using the flower pot procedure or kept in home cage. On day 24, fronto-parietal electroencephalogram, electromyogram and motility were recorded in the first 2 h of the passive phase. The observed sleep patterns were characterized applying standard sleep metrics, by modelling the transitions between sleep phases using Markov chains and by spectral analysis.Based on Markov chain analysis, chronic escitalopram treatment attenuated the REM sleep fragmentation [accelerated transition rates between REM and non-REM (NREM) stages, decreased REM sleep residence time between two transitions] during the rebound sleep. Additionally, the antidepressant avoided the frequent awakenings during the first 30 min of recovery period. The spectral analysis showed that the SSRI prevented the RD-caused elevation in theta (5 inverted question mark9 Hz) power during slow-wave sleep. Conversely, based on the aggregate sleep metrics, escitalopram had only moderate effects and it did not significantly attenuate the REM rebound after RD.ConclusionIn conclusion, chronic SSRI treatment is capable of reducing several effects on sleep which might be the consequence of the sub-chronic stress caused by the flower pot method. These data might support the antidepressant activity of SSRIs, and may allude that investigating the rebound period following the flower pot protocol could be useful to detect antidepressant drug response. Markov analysis is a suitable method to study the sleep pattern

Monitoring Toxicity Associated with Parenteral Sodium Stibogluconate in the Day-Case Management of Returned Travellers with New World Cutaneous Leishmaniasi

Sodium stibogluconate (SbV), a pentavalent antimonial, administered parenterally, is the recommended treatment for South American cutaneous leishmaniasis, caused by Leishmania Viannia, which is a neglected disease that affects many people resident in Central and South America, as well as travellers to the areas. Antimonials have been used for the treatment of leishmaniasis since the 1930s. We report the toxicity experienced by a series of NWCL patients receiving SbV in a resource-rich setting. This study also evaluates administration of the drug to patients without admitting them to hospital. The administration of parenteral SbV was associated with myelosuppression, derangement of markers of liver function and prolongation of the QT interval on electrocardiography, although these effects were not found to be associated with adverse clinical events, and the majority of doses of SbV were administered without cause for hospital admission. Our data shows that parenteral SbV treatment may be provided with reduced monitoring for toxicity than is currently done, and on an outpatient-basis, without endangering safety. Such practice, with reduced demands on local finances and the healthcare workforce, would be desirable in more resource-limited settings

Responsiveness to exercise training in juvenile dermatomyositis: a twin case study

<p>Abstract</p> <p>Background</p> <p>Patients with juvenile dermatomyositis (JDM) often present strong exercise intolerance and muscle weakness. However, the role of exercise training in this disease has not been investigated.</p> <p>Purpose</p> <p>this longitudinal case study reports on the effects of exercise training on a 7-year-old patient with JDM and on her unaffected monozygotic twin sister, who served as a control.</p> <p>Methods</p> <p>Both the patient who was diagnosed with JDM as well as her healthy twin underwent a 16-week exercise training program comprising aerobic and strengthening exercises. We assessed one repetition-maximum (1-RM) leg-press and bench-press strength, balance, mobility and muscle function, blood markers of inflammation and muscle enzymes, aerobic conditioning, and disease activity scores. As a result, the healthy child had an overall greater absolute strength, muscle function and aerobic conditioning compared to her JDM twin pair at baseline and after the trial. However, the twins presented comparable relative improvements in 1-RM bench press, 1-RM leg press, VO_2peak, and time-to-exhaustion. The healthy child had greater relative increments in low-back strength and handgrip, whereas the child with JDM presented a higher relative increase in ventilatory anaerobic threshold parameters and functional tests. Quality of life, inflammation, muscle damage and disease activity scores remained unchanged.</p> <p>Results and Conclusion</p> <p>this was the first report to describe the training response of a patient with non-active JDM following an exercise training regimen. The child with JDM exhibited improved strength, muscle function and aerobic conditioning without presenting an exacerbation of the disease.</p

COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance

OBJECTIVE: To describe coronavirus disease-2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020 the COVID-19 Global Rheumatology Alliance (GRA) has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included: rheumatoid arthritis (n=9), systemic lupus erythematosus (n=9), psoriatic/other inflammatory arthritides (n=8) and anti-phospholipid antibody syndrome (n=6). Most had a term birth (16/22), with 3 pre-term births, one termination, one miscarriage and one woman yet to deliver at time of report. A quarter (n=10/39) of pregnant women were hospitalised following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalised); no patient died. The majority did not receive specific medication treatment for their COVID-19 (n=32/39, 82%), seven patients received some combination of anti-malarials, colchicine, anti-IL-1beta, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favourable outcomes. These data have limitations due to the small size and methodology, though they provide cautious optimism for pregnancy outcomes for women with rheumatic disease given the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19